Amorphous solid dispersion and pharmaceutical composition comprising same

Abstract

Provided is a pharmaceutical composition comprising an amorphous solid dispersion comprising: i) a lipophilic active pharmaceutical ingredient, such as abiraterone, alectinib, pazopanib, cabozantinib, vetoclax, lurasidone, or vilazodone, or a salt thereof, and i) a lipophilic active pharmaceutical ingredient, such as abiraterone, alectinib, pazopanib, cabozantinib, vetoclax, lurasidone, or vilazodone, or a salt thereof; ii) a hydrophilic polymer; iii) optionally a surfactant; iv) optionally an adsorbent; and v) optionally an acid. Also described are methods for preparing such pharmaceutical compositions and treating a subject in need thereof. In one aspect, disclosed herein is an amorphous solid dispersion comprising an active pharmaceutical ingredient.

Description

[0001] Cross-referencing related applications

[0002] This application claims the benefit of patent application No. PCT / CN2022 / 083103 filed on March 25, 2022 and patent application No. PCT / CN2023 / 080338 filed on March 8, 2023, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] This invention belongs to the pharmaceutical field, and specifically relates to pharmaceutical compositions, their preparation methods, and uses. Background Technology

[0004] Many active pharmaceutical ingredients (APIs) are compounds with poor water solubility, low oral bioavailability, and food effects upon oral administration. Some examples of these APIs are abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, and vilazodone. Therefore, there is a need for improved compositions for such APIs to provide better oral bioavailability, allow for lower doses, and reduce absorption variability caused by food intake and differences in absorption among subjects.

[0005] By incorporating via reference

[0006] All publications and patent applications mentioned in this specification are incorporated herein by reference to the extent that each individual publication or patent application is specifically and individually indicated to be incorporated by reference. Summary of the Invention

[0007] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is cabozantinib or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; d) optionally an acid; and e) optionally an adsorbent.

[0008] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is venetoclax or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5% to about 50% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; d) optionally an acid; and e) optionally an adsorbent.

[0009] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is abiraterone or abiraterone acetate; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; d) optionally an acid; and e) optionally an adsorbent.

[0010] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is abiraterone or abiraterone acetate; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), polyethylene glycol and The ASD comprises: a) a block copolymer of polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; b) a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 1% to about 95% by weight of the ASD; c) optionally an acid, wherein the amount of the acid is from about 5% to 60% by weight of the ASD; and e) optionally an adsorbent, wherein the amount of the adsorbent is from about 1% to 60% by weight of the ASD.

[0011] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is alectinib or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol ester, polysorbate ester, or combinations thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; d) optionally an acid; and e) optionally an adsorbent.

[0012] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is alectinib or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), or polyethylene glycol. The ASD may contain: c) a block copolymer of polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; d) a hydrophilic polymer in an amount of about 1% to about 95% by weight of the ASD; e) optionally an acid in an amount of about 5% to 40% by weight of the ASD; and e) optionally an adsorbent in an amount of about 1% to 50% by weight of the ASD.

[0013] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is pazopanib or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; d) optionally an acid; and e) optionally an adsorbent.

[0014] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is pazopanib or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), or polyethylene glycol. The ASD may contain: c) a block copolymer of polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; d) a hydrophilic polymer in an amount of about 1% to about 95% by weight of the ASD; e) optionally an acid in an amount of about 5% to 60% by weight of the ASD; and e) optionally an adsorbent in an amount of about 1% to 60% by weight of the ASD.

[0015] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 3% to about 60% by weight of the ASD, wherein the API is lurasidone or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; d) optionally an acid; and e) optionally an adsorbent.

[0016] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is lurasidone or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), or polyethylene glycol. The ASD may contain: c) a block copolymer of polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; d) a hydrophilic polymer in an amount of about 1% to about 95% by weight of the ASD; e) optionally an acid in an amount of about 5% to 60% by weight of the ASD; and e) optionally an adsorbent in an amount of about 1% to 60% by weight of the ASD.

[0017] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is vilazorone or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol ester, polysorbate ester, or a combination thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; d) optionally an acid; and e) optionally an adsorbent.

[0018] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is vilazorone or a pharmaceutically acceptable salt thereof; b) optionally a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), or polyethylene glycol. The ASD may contain: c) a block copolymer of polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof; d) a hydrophilic polymer in an amount of about 1% to about 95% by weight of the ASD; e) optionally an acid in an amount of about 5% to 60% by weight of the ASD; and e) optionally an adsorbent in an amount of about 1% to 60% by weight of the ASD.

[0019] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) selected from abiraterone, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, vilazorone, and pharmaceutically acceptable salts thereof; b) a surfactant comprising a phospholipid or a derivative thereof; c) a hydrophilic polymer; and d) optionally an adsorbent.

[0020] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD) comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 35% by weight of the ASD, wherein the API is cabozantinib or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises phospholipids or derivatives thereof, or lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, a graft copolymer based on polyvinylcaprolactam (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, or a combination thereof; c) a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD; and d) optionally an adsorbent in an amount of about 1% to 40% by weight of the ASD, wherein the adsorbent is silica.

[0021] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 45% by weight of the ASD, wherein the API is venetoclax or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5% to about 50% by weight of the ASD, wherein the surfactant comprises phospholipids or derivatives thereof, such as lecithin, block copolymers of polyethylene glycol and polypropylene glycol, T... PGS, a graft copolymer based on polyvinylcaprolactam (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, or a combination thereof; c) a nonionic hydrophilic polymer, said nonionic hydrophilic polymer in an amount of about 1% to about 80% by weight of said ASD; d) optionally an inorganic or organic acid, said inorganic or organic acid in an amount of about 1% to 20% by weight of said ASD; and e) optionally an adsorbent, said adsorbent in an amount of about 1% to 40% by weight of said ASD, said adsorbent being silica.

[0022] This document discloses a pharmaceutical composition comprising an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5% to about 60% by weight of the ASD, wherein the API is selected from abiraterone acetate, alectinib hydrochloride, pazopanib hydrochloride, lurasidone, vilazorone, and pharmaceutically acceptable salts thereof; b) a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof. The ASD may contain, for example, lecithin, block copolymers of polyethylene glycol and polypropylene glycol, TPGS, graft copolymers based on polyvinyl caprolactam (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, or combinations thereof; c) a hydrophilic polymer, the amount of which is from about 1% to about 90% by weight of the ASD; d) optionally an inorganic or organic acid, the amount of which is from about 5% to 40% by weight of the ASD; and e) optionally an adsorbent, the amount of which is from about 1% to 40% by weight of the ASD.

[0023] This document discloses an amorphous solid dispersion (ASD) comprising: a) cabozantinib free base or cabozantinib malate; b) a surfactant; c) a hydrophilic polymer; d) optionally an adsorbent; and e) optionally an organic acid.

[0024] This article discloses a method for treating a disease or condition, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein.

[0025] This document discloses a method for treating cancer, the method comprising administering a pharmaceutical composition or amorphous solid dispersion described herein to a subject in need. In some embodiments, the cancer includes renal cell carcinoma, liver cancer, and thyroid cancer. In some embodiments, the renal cell carcinoma is advanced renal cell carcinoma. In some embodiments, the liver cancer is hepatocellular carcinoma. In some embodiments, the thyroid cancer is locally advanced or metastatic differentiated thyroid cancer or medullary thyroid carcinoma.

[0026] This document discloses a method for inhibiting multiple tyrosine kinases, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the multiple tyrosine kinases comprise VEGFR2, c-MET, or RET. In some embodiments, the method further comprises administering an immunotherapeutic agent. In some embodiments, the immunotherapeutic agent is nivolumab. In some embodiments, the subject has previously been treated with sorafenib. In some embodiments, a) the subject is 12 years of age or older, b) the subject has progressed after prior VEGFR-targeted therapy; and c) the subject is radioiodine refractory or ineligible.

[0027] This document discloses an amorphous solid dispersion (ASD) comprising: a) vennetotox or a pharmaceutically acceptable salt thereof; b) a surfactant; c) a hydrophilic polymer; d) optionally an organic acid; and e) optionally an adsorbent.

[0028] This article discloses a method for treating a disease or condition, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein.

[0029] This document discloses a method for treating cancer, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the cancer is a blood cancer. In some embodiments, the blood cancer is chronic lymphocytic leukemia. In some embodiments, the blood cancer is acute myeloid leukemia. In some embodiments, the cancer is a solid tumor. In some embodiments, the solid tumor is lymphoma. In some embodiments, the lymphoma is small lymphocytic lymphoma.

[0030] This document discloses a method for inhibiting B-cell lymphoma-2 (Bcl-2) protein, the method comprising administering the pharmaceutical composition or amorphous solid dispersion described herein to a subject in need. In some embodiments, the method further comprises administering an immunotherapeutic agent. In some embodiments, the immunotherapeutic agent is obinutuzumab or rituximab. In some embodiments, the method further comprises administering a chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is azacitidine, or decitabine, or low-dose cytarabine. In some embodiments, the subject is previously untreated. In some embodiments, the subject has been previously treated. In some embodiments, a) the subject is newly diagnosed with acute myeloid leukemia, and b) the subject is 75 years of age or older, or c) the subject has other medical conditions that prevent the use of standard chemotherapy. In some embodiments, the subject is an adult.

[0031] This document discloses an amorphous solid dispersion (ASD) comprising: a) abiraterone free base or abiraterone acetate; b) a hydrophilic polymer; c) optionally a surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

[0032] This article discloses a method for treating a disease or condition, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein.

[0033] This document discloses a method for treating cancer, the method comprising administering to a subject of need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the cancer is a solid tumor. In some embodiments, the solid tumor is prostate cancer. In some embodiments, the prostate cancer is metastatic castration-resistant prostate cancer. In some embodiments, the prostate cancer is metastatic high-risk castration-sensitive prostate cancer.

[0034] This document discloses a method for inhibiting 17α-hydroxylase / C17,20-lyase (CYP17), the method comprising administering to a subject of need the pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the method further comprises administering a corticosteroid. In some embodiments, the corticosteroid is prednisone or methylprednisolone. In some embodiments, the method further comprises administering a corticosteroid. In some embodiments, the corticosteroid is methylprednisolone. In some embodiments, the subject is a male adult.

[0035] This document discloses an amorphous solid dispersion (ASD) comprising: a) alectinib free base or alectinib hydrochloride; b) a hydrophilic polymer; c) a surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

[0036] This article discloses a method for treating a disease or condition, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein.

[0037] This document discloses a method for treating cancer, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the cancer is a solid tumor. In some embodiments, the solid tumor is lung cancer. In some embodiments, the lung cancer is non-small cell lung cancer. In some embodiments, the non-small cell lung cancer is anaplastic lymphoma kinase (ALK)-positive metastatic high-risk castration-sensitive prostate cancer.

[0038] This document discloses a method for inhibiting ALK and / or RET tyrosine kinases, the method comprising administering the pharmaceutical composition or amorphous solid dispersion described herein to a subject in need. In some embodiments, the subject is an adult. In some embodiments, the subject is intolerant to crizotinib.

[0039] This document discloses an amorphous solid dispersion (ASD) comprising: a) a pazopanib free base or pazopanib hydrochloride; b) a hydrophilic polymer; c) a surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

[0040] This article discloses a method for treating a disease or condition, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein.

[0041] This document discloses a method for treating cancer, the method comprising administering to a subject of need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the cancer is a solid tumor. The solid tumor is a soft tissue sarcoma. In some embodiments, the soft tissue sarcoma is an advanced soft tissue sarcoma. In some embodiments, the cancer is renal cell carcinoma. In some embodiments, the renal cell carcinoma is an advanced renal cell carcinoma.

[0042] This document discloses a method for inhibiting tyrosine kinases of VEGF receptor (VEGFR) and / or PDGF receptor (PDGFR), the method comprising administering the pharmaceutical composition or amorphous solid dispersion described herein to a subject in need. In some embodiments, the subject is an adult. In some embodiments, the subject has previously received chemotherapy.

[0043] This document discloses an amorphous solid dispersion (ASD) comprising: a) a lourazidone free base or lourazidone hydrochloride; b) a hydrophilic polymer; c) a surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

[0044] This article discloses a method for treating a disease or condition, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein.

[0045] This document discloses a method for treating a mental disorder, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the mental disorder is schizophrenia. In some embodiments, the mental disorder is depression. In some embodiments, the depression is associated with bipolar I disorder. In some embodiments, the depression is bipolar depression.

[0046] This document discloses a method for inhibiting central dopamine D2 and serotonin type 2 (5HT2A) receptors, the method comprising administering the pharmaceutical composition or amorphous solid dispersion described herein to a subject in need. In some embodiments, the subject is an adult. In some embodiments, the adolescent is 13 to 17 years of age. In some embodiments, the method further comprises administering an anticonvulsant. In some embodiments, the anticonvulsant is lithium or valproate.

[0047] This document discloses an amorphous solid dispersion (ASD) comprising: a) a free base of vilazorone or vilazorone hydrochloride; b) a hydrophilic polymer; c) a surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

[0048] This article discloses a method for treating a disease or condition, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein.

[0049] This document discloses a method for treating a mental disorder, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the mental disorder is major depressive disorder.

[0050] This document discloses a method for inhibiting serotonin (5-HT1A) receptors, the method comprising administering the pharmaceutical composition or amorphous solid dispersion described herein to a subject in need. In some embodiments, the subject is an adult.

[0051] This document discloses a method for stimulating a serotonin transporter, the method comprising administering to a subject in need a pharmaceutical composition or amorphous solid dispersion described herein. In some embodiments, the stimulation is performed by partial activation. In some embodiments, the subject is an adult. Attached Figure Description

[0052] This document provides pharmaceutical compositions comprising amorphous solid dispersions containing such APIs, and suitable excipients or carriers provide improved bioavailability and eliminate or reduce food effects compared to existing compositions comprising crystalline forms of such APIs. The novel features of the invention are specifically set forth in the appended claims. A better understanding of the features and advantages of the invention will be obtained by referring to the following detailed description of illustrative embodiments, which utilize the principles of the invention, and in the accompanying drawings:

[0053] Figure 1A X-ray powder diffraction studies of two amorphous solid dispersion (ASD) batches, P211115-2 and P211115-1, of abiraterone acetate are shown, both of which were in an amorphous state.

[0054] Figure 1B A comparison of X-ray powder diffraction of two amorphous solid dispersions (ASDs) of abiraterone acetate API and abiraterone acetate API (P211115-2 and P211115-1) is shown. The two ASDs are in an amorphous state, while abiraterone acetate API is not in an amorphous state.

[0055] Figure 1CThe study presents a comparison of plasma concentrations of the reference product ZYTIGA (250 mg) and two ASD compositions of abiraterone (batch numbers P211115-1 and P211115-2) in a canine model when administered orally at a dose of 50 mg API under fasting conditions.

[0056] Figure 2A X-ray powder diffraction studies of four solid dispersion batches of crystalline alectinib hydrochloride, namely I-M211221-1, I-M211221-3, I-M211202-3 and I-M211229-1, are shown. Batch I-M211202-3 is mostly amorphous, and all other batches are in an amorphous state.

[0057] Figure 2B X-ray powder diffraction studies of six solid dispersion batches of alectinib hydrochloride, I-M221214-1, I-M221214-2, I-M221214-3, I-M221214-4, I-M221214-5 and I-M221214-6, are shown. All batches were in an amorphous state.

[0058] Figure 3 The kinetic solubility of four ASD batches of alectinib hydrochloride, I-M211221-1, I-M211221-3, I-M211202-3 and I-M211229-1, as determined by HPLC, is shown.

[0059] Figure 4A X-ray powder diffraction studies of three ASD batches of pazopanib hydrochloride, M210706-1, M210706-2 and M211214-2, are shown, all of which were in an amorphous state.

[0060] Figure 4B X-ray powder diffraction studies of five ASD batches of pazopanib hydrochloride, M221222-2, M221222-3, M221222-4, M230104-2 and M230104-3, are shown. All of these batches were in an amorphous state.

[0061] Figure 5A X-ray powder diffraction studies of three ASD batches of cabozantinib malate, M210702-1-I, M210702-2-I and M210702-3-I, are shown. All of these batches were in an amorphous state.

[0062] Figure 5BX-ray powder diffraction studies of five ASD batches of cabozantinib malate, M220701-1, M220701-2, M220622-3, M220622-4 and M220714, are shown. All of these batches were in an amorphous state.

[0063] Figure 6 The kinetic solubility of cabozantinib malate in three ASD batches M210702-1-I, M210702-2-I and M210702-3-I, as determined by HPLC, is shown.

[0064] Figure 7A X-ray powder diffraction studies of two ASD batches, M210618-1-I and M210618-2-I, of Venetok are shown, both of which were in an amorphous state.

[0065] Figure 7B X-ray powder diffraction studies of four ASD batches I-M220808-3, I-M220630-2, I-M220727-2 and I-M221010-1 from Vinnetock are shown, all of which were in an amorphous state.

[0066] Figure 7C X-ray powder diffraction studies of Venetok's ASD batches I-M221219-1, I-M221219-2, I-M221219-3, I-M221221-1, I-M221221-2, I-M221221-3 and I-M221221-4 are shown, all of which are in an amorphous state.

[0067] Figure 8A The kinetic solubility of two ASD batches of venetoclax, M210618-1-I and M210618-2-I, as determined by HPLC, is shown.

[0068] Figure 8B The mean PK curves in rat models of venetoclax RLD tablets ground into powder and venetoclax ASD powder from batches I-M221201-2, I-M221118, I-M221219-1 and I-M221219-2, all of which were suspended in 0.5% CMC-Na solution prior to administration are shown.

[0069] Figure 9A X-ray powder diffraction studies of three ASD batches of lurasidone, I-M211207-2, I-M211209-4 and M211028-1, are shown, all of which were in an amorphous state.

[0070] Figure 9B X-ray powder diffraction studies of five ASD batches of lurasidone, I-M211207-2, I-M211209-4, M211028-1, M211101-1 and M211101-2, are shown. All of these batches were in an amorphous state.

[0071] Figure 9C X-ray powder diffraction studies of three ASD batches of lurasidone, I-M211207-3, I-M211207-4 and I-M220712-1, are shown, all of which were in an amorphous state.

[0072] Figure 10 The kinetic solubility of lurasidone in three ASD batches I-M211207-2, I-M211209-4 and M211028-1, as determined by HPLC, is shown.

[0073] Figure 11 X-ray powder diffraction study of ASD batch P210324-1 of lurasidone in an amorphous state is shown.

[0074] Figure 12A The kinetic solubility of crystalline lumrazone (API) and lumrazone ASD batch P210324-1 in FeSSIF medium, as determined by HPLC, is shown.

[0075] Figure 12B The kinetic solubility of crystalline lumrazone (API) and lumrazone ASD batch P210324-1 in FaSSIF medium, as determined by HPLC, is shown.

[0076] Figure 13A X-ray powder diffraction studies of ASD batch P210324-1 vilazone in an amorphous state are shown.

[0077] Figure 13B X-ray powder diffraction studies of vilazorone API in crystalline form and vilazorone in amorphous form (ASD batch P210324-1) are shown.

[0078] Figure 14 The kinetic solubility of crystalline vilazorone and vilazorone ASD batch P210324-1 in FaSSIF and FeSSIF media, as determined by HPLC, is shown. Detailed Implementation

[0079] This invention generally relates to compositions comprising a pharmaceutically active agent that can be used as a therapeutic agent to relieve, reduce, or eliminate one or more symptoms in a subject in need, as further described herein. Specifically, pharmaceutical compositions, their synthesis, and uses are described herein, wherein the pharmaceutical composition comprises a combination of a lipophilic API, a hydrophilic polymer, and a surfactant, such that the API has improved bioavailability compared to the API alone. In some embodiments, the lipophilic API, the hydrophilic polymer, and the surfactant are in an amorphous solid dispersion. In some embodiments, the pharmaceutical composition optionally comprises one or more adsorbents. In some embodiments, the pharmaceutical composition optionally comprises one or more organic or inorganic acids.

[0080] definition

[0081] Unless specifically stated or obvious from the context, as used herein, the term “about” in numbers or ranges means + / - 10% of the stated number and its numerals, or 10% of the value in the range that is below the lower limit and above the upper limit.

[0082] Unless the context clearly indicates otherwise, the singular forms “a / an” and “the” include plural referents. Thus, for example, referring to “surfactant” includes referring to one or more specific surfactants, and referring to “antioxidant” includes referring to one or more of such additives.

[0083] As used in this article, the term “subject” refers to mammals (e.g., humans, mice, rats, guinea pigs, dogs, cats, horses, cattle, pigs, or non-human primates such as monkeys, chimpanzees, or baboons).

[0084] As used in this article, “AUC” or “AUC” inf "AUC" refers to the area under the plasma drug concentration versus time curve extrapolated from zero to infinity. As used in this article, "AUC" is... last "C" refers to the area under the curve from the time of drug administration to the time to the final measurable concentration. For example, "C" is used in this article. max "T" refers to the highest drug concentration observed in plasma after extravascular administration. For example, "T" as used in this article... max "This refers to the time it takes to reach the highest plasma concentration after drug administration."

[0085] As used herein, “D10,” “D50,” and “D90” are used to describe particle size distribution. “D10,” as used herein, refers to the diameter of the 10th percentile of the total mass of particles that are smaller than 90 percent. “D50,” as used herein, refers to the median diameter of the 50th percentile of the total mass of particles that are larger than 50 percent. “D90” defines the diameter of the mass distribution where 90 percent of the particles have smaller diameters and 10 percent have larger diameters.

[0086] In some embodiments, the error band is included. The term "total error band" is used herein to describe the total error band, calculated at a 95% confidence level, encompassing all sources including sampling and sample preparation. An example is a total error band of + / -5% for a D50 100 μm size. Other statistical data are sometimes used to describe particle size distribution. The most common calculations are standard deviation and variance. Standard deviation (St Dev.). The standard deviation specification defines the diameter when approximately 68.27% of the total population lies within + / -1 St Dev, and 95.45% lies within + / -2 St Dev.

[0087] "Effective amount" and "sufficient amount" can be used interchangeably, and both refer to the amount of substance sufficient to achieve the intended purpose or goal.

[0088] When used in conjunction with the pharmaceutical compositions described herein, a “therapeutic effective amount” is an amount of one or more pharmaceutically active agents sufficient to produce a therapeutic outcome in a subject in need.

[0089] When used in conjunction with the pharmaceutical compositions described herein, "therapeutic equivalent" means an amount or quantity of a pharmaceutically acceptable salt or ester of the active pharmaceutical ingredient that is equivalent to a therapeutically effective amount of the free base or alcohol of the active pharmaceutical ingredient.

[0090] Active pharmaceutical ingredient (API)

[0091] On the one hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an active pharmaceutical agent. The various embodiments described herein relate to compositions comprising an effective amount of an active pharmaceutical agent (API). The terms “active pharmaceutical agent,” “API,” “pharmaceutical,” “pharmaceutical active agent,” “bioactive agent,” “therapeutic agent,” and “active agent” are used interchangeably and refer to substances, such as chemical compounds or complexes, that, when administered in an effective amount, have a measurable beneficial physiological effect on the body, such as a therapeutic effect in the treatment of a disease or condition. Furthermore, when using these terms, or when a particular active agent is specifically identified by name or category, it should be understood that such descriptions are intended to include the active agent itself, as well as pharmaceutically acceptable pharmacologically active derivatives thereof, or compounds significantly associated therewith, including but not limited to salts, pharmaceutically acceptable salts, N-oxides, prodrugs, active metabolites, isomers, fragments, analogs, solvates, hydrates, radioisotopes, etc.

[0092] As mentioned herein, the partition coefficient (P) is the ratio of the concentrations of a compound in two immiscible solvent phases at equilibrium. Most typically, one solvent is water, and the other is hydrophobic, usually 1-octanol. The logarithm of the ratio is log P, as shown below (by convention, the lipophilic phase is the numerator and the hydrophilic phase is the denominator).

[0093]

[0094] log P is a measure of lipophilicity or hydrophobicity. Hydrophobicity affects drug absorption, bioavailability, hydrophobic drug-receptor interactions, molecule metabolism, and toxicity. Hydrophilic compounds are soluble in water (“water-loving”) and polar solvents. Lipophilic compounds are less soluble in water (“hydrophobic”) and polar solvents, but more soluble in organic solvents. Therefore:

[0095] Low hydrophilicity = high lipophilicity = high log P = poor water solubility = poor absorption.

[0096] High hydrophilicity = low lipophilicity = low log P = good water solubility = good absorption.

[0097] The partition coefficient can be measured experimentally or estimated by calculation. Various methods have been developed for calculating (or predicting) log P, typically trained on a set of thousands of molecules, mostly drugs, by fitting the calculated log P value to the experimentally measured log P value. Log P calculations are considered very robust and accurate for many organic molecules. For example, the prediction error for log P is less than 0.25 for over 50% of molecules, and less than 0.5 for over 80%. Less than 3.5% of structures have a prediction error greater than 1.0. To distinguish it from the measured log P, the calculated log P is sometimes written as clog P. Unless otherwise specified, “log P” as used herein refers to the experimental log P value.

[0098] In some embodiments, the API is lipophilic. An API is considered lipophilic if its log P or calculated log P is 2.0 or higher. A log P of 2.0 or higher indicates that the API's solubility in a lipophilic solvent is 100 times or more than its solubility in water. In some embodiments, the API is insoluble in polar solvents. In some embodiments, the API is insoluble in aqueous media. In some embodiments, the API is insoluble in water.

[0099] In some embodiments, the log P of the lipophilic API is at least 2.0, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7.0. Exemplary small molecule lipophilic APIs include, but are not limited to, the small molecule lipophilic APIs listed in Table 1.

[0100] Table 1

[0101] name The calculated log P Experimental log P Abiraterone acetate <![CDATA[5.1 1 ]]> <![CDATA[5.12 2 ]]> Pazopanib <![CDATA[3.59 3 ]]> Unavailable Alectinib <![CDATA[5.59 1 ]]> Unavailable Cabozantinib malate <![CDATA[4.01 1 ]]> -- Vinetok <![CDATA[6.92 1 ]]> Lurasidone <![CDATA[5.4 1 ]]> -- Virazodone <![CDATA[3.72 3 ]]> --

[0102] 1 Calculation source - ALOGPS listed at www.drugbank.ca

[0103] 2 Experimental values ​​listed on drug labels

[0104] 3 Calculation source - listed on www.drugbank.ca by ChemAxon

[0105] The acid dissociation constant Ka (or acidity constant) is a measure of the strength of an acid or base in solution, usually water. For the chemical dissociation of acids and bases, the acid dissociation constant is an equilibrium constant. In aqueous solution, the equilibrium equation for acid dissociation is written as:

[0106]

[0107] HA is an acid, which dissociates into A. - (The conjugate base of the acid) and hydrogen ions (which combine with water molecules to form hydrated hydrogen ions H3O) + The dissociation constant can also be written with H2O removed:

[0108]

[0109] The dissociation equilibrium of a base and its conjugate acid is written as:

[0110]

[0111] Among them BH + (The conjugate acid of the base) dissociates into B (free base) and hydrogen ions, which combine with water molecules to form hydrated hydrogen ions H3O. + .

[0112] The dissociation constant can also be written with H2O removed:

[0113]

[0114] K a logarithmic value pK a More commonly used to express the acid strength / weakness of the conjugate acid of an acid or base:

[0115] pK a =-log 10 (K a )

[0116] pK a The more positive the value, the less dissociated the acid, and the weaker the acid. Generally, for acids:

[0117] pK a = -2 to 12 → weak acid (dissociates little or only partially in water)

[0118] pKa < -2 → strong acid (completely or mostly dissociates in water)

[0119] As for alkalis:

[0120] pK a <12 → Weak base (dissociates little or only partially in water)

[0121] pKa ≥ 12 → Strong base (completely or mostly dissociates in water)

[0122] In some embodiments, the API is a weak base.

[0123] In some embodiments, the API contains a weak base functional group.

[0124] In some embodiments, the pKa of the API is equal to or greater than 3.0. In some embodiments, the pKa of the API is equal to or greater than 3.5. In some embodiments, the pKa of the API is equal to or greater than 4.0. In some embodiments, the pKa of the API is equal to or greater than 4.5. In some embodiments, the pKa of the API is equal to or greater than 5.0.

[0125] In some embodiments, the API is present as a free base. In some embodiments, the API is present as a pharmaceutically acceptable salt. As used herein, pharmaceutically acceptable salts include, but are not limited to, metal salts such as sodium, potassium, and lithium salts; alkaline earth metals such as calcium and magnesium salts; organic amine salts such as triethylamine, pyridine, methylpyridine, ethanolamine, triethanolamine, dicyclohexylamine, and N,N'-dibenzylethylenediamine; inorganic acid salts such as hydrochloride, hydrobromide, sulfate, and phosphate; organic acid salts such as formate, acetate, trifluoroacetate, maleate, and tartrate; sulfonates such as methanesulfonate, benzenesulfonate, and p-toluenesulfonate; and amino acid salts such as arginine, aspartate, and glutamate. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, vilazorone, or a pharmaceutically acceptable salt or ester thereof. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone. In some embodiments, the API is a pharmaceutically acceptable salt of abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone. In some embodiments, the API is a lipophilic API. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the API is selected from the APIs in Table 1. In some embodiments, the API has a log P of 2.0 or higher. In some embodiments, the API has a log P of 3.0 or higher. In some embodiments, the API has a log P of 3.5 or higher. In some embodiments, the API has a log P of 4.0 or higher. In some embodiments, the API has a log P of 4.5 or higher. In some embodiments, the lipophilic API, hydrophilic polymer, and surfactant are formulated into an amorphous solids dispersion. In some embodiments, the amorphous solids dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solid dispersions described herein further comprise one or more adsorbents. In some embodiments, the amorphous solid dispersions described herein further comprise one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0126] Pharmaceutically acceptable salts include tartrate, tartrate hydrochloride, hydrochloride, p-toluenesulfonate, phosphate, sulfate, trifluoroacetate, tartrate hemipentahydrate, pentafluoropropionate, hydrobromide, mucilage, oleate, diphosphate, monophosphate, acetate trihydrate, bis(heptafluorobutyrate), bis(pentafluoropropionate), bis(pyridinecarboxylate), bis(trifluoroacetate), hydrochloride, and sulfate pentahydrate. Other representative pharmaceutically acceptable salts include, for example, water-soluble and insoluble salts such as acetates, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonates, benzoates, bicarbonates, bisulfates, tartrates, borates, butyrates, calcium edetate, camphorsulfonate (or camsylate), carbonates, citrates, clavulariate, dihydrochlorides, ethylenediaminetetraacetate, ethanedisulfonate, propionate, dodecyl sulfate, ethanesulfonate, fumarate (or fumarate), glucono-p-aminobenzoarsylate, gluconate, glutamate, glycolyl-p-aminobenzoarsylate, hexafluorophosphate, hexylresorcinol, hydrabamine, and hydrobromide. Salts, hydrochlorides, hydroxynaphthylcarboxylate, iodides, 19ydroxyapat, lactates, lacturonates, laurates, malates, maleates, mandelates, methanesulfonates, methyl bromide, methyl nitrates, methyl sulfates, mucilages, naphthalenesulfonates, nitrates, N-methylglucosamine ammonium salts, 3-hydroxy-2-naphthylcarboxylate, oleates, oxalates, palmitates, bis(hydroxynaphthyl)ate (1,1-methylene-bis-2-hydroxy-3-naphthylcarboxylate, einbonate), pantothenates, phosphates / bisphosphonates, picrates, polygalacturonates, propionates, p-toluenesulfonates, salicylates, stearates, basic acetates, succinates, sulfates, sulfosalicylates, suramates, tannins, tartrates, theochloroate, toluenesulfonates, triethyliodide, and valerates. Hydrates are another example of pharmaceutically acceptable salts. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, vilazodone, or a pharmaceutically acceptable salt thereof. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone, or a pharmaceutically acceptable salt thereof.

[0127] In the presence of negatively charged free radicals such as carboxyl or sulfonyl groups, it can also form salts with bases, such as metal or ammonium salts like alkali metal or alkaline earth metal salts, such as sodium, potassium, magnesium or calcium salts, or ammonium salts with ammonia or suitable organic amines such as tertiary monoamines, such as triethylamine or tri(2-hydroxyethyl)amine or heterocyclic bases, such as N-ethyl-piperidine or N,N'-dimethylpiperazine.

[0128] The compounds disclosed herein can also form internal salts when a basic group and an acidic group are present in the same molecule. Pharmaceutically unacceptable salts, such as picrates or perchlorates, may also be used for separation or purification purposes. For therapeutic uses, only pharmaceutically acceptable salts or free compounds (in pharmaceutical formulations where applicable) are used, and therefore these are preferred.

[0129] In some embodiments, the API is a lipophilic API. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the log P of the lipophilic API is 2.0 or higher. In some embodiments, the log P of the lipophilic API is 3.0 or higher. In some embodiments, the amorphous solid dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solid dispersion described herein further comprises one or more adsorbents. In some embodiments, the amorphous solid dispersion described herein further comprises one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0130] In some embodiments, the API has low solubility at pH values ​​of about 6-8. In some embodiments, the API has a solubility of less than 10 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 1.0 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 0.5 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 0.1 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 0.05 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 0.04 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 0.03 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 0.02 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the API has a solubility of less than 0.01 mg / ml in solutions with pH values ​​between about 6-8. In some embodiments, the solubility of an API in a solution with a pH between about 6 and 8 is less than 0.001 mg / ml. In some embodiments, the API has low solubility at pH levels between about 4 and 8. In some embodiments, the API has a solubility of less than 10 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 1.0 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.5 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.1 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.05 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.04 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.03 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.02 mg / ml in a solution with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.01 mg / ml in solutions with a pH between about 4 and 8. In some embodiments, the API has a solubility of less than 0.001 mg / ml in solutions with a pH between about 4 and 8. In some embodiments, the API has low solubility at pH levels between about 6 and 10. In some embodiments, the API has a solubility of less than 10 mg / ml in solutions with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 1.0 mg / ml in solutions with a pH between about 6 and 10.In some embodiments, the API has a solubility of less than 0.5 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 0.1 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 0.05 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 0.04 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 0.03 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 0.02 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 0.01 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API has a solubility of less than 0.001 mg / ml in a solution with a pH between about 6 and 10. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, vilazorone, or a pharmaceutically acceptable salt thereof. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, or vilazodone. In some embodiments, the API is a pharmaceutically acceptable salt of abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, or vilazodone. In some embodiments, the API is a lipophilic API. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the lipophilic API has a log P of 2.0 or higher. In some embodiments, the amorphous solids dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solids dispersion described herein further comprises one or more adsorbents. In some embodiments, the amorphous solids dispersion described herein further comprises one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0131] This document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API, a hydrophilic polymer, optionally a surfactant, and optionally an adsorbent. In some embodiments, the ASD is formulated as part of the pharmaceutical composition in a unit dosage form such as a capsule or tablet. In some embodiments, the API is present in the ASD in an amount of at least 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 75 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 175 mg, 180 mg, 190 mg, or 200 mg. In some embodiments, the API is present in ASD in amounts of about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 75 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 175 mg, 180 mg, 190 mg, or 200 mg. In some embodiments, the API is present in ASD in amounts not exceeding 1000 mg, 750 mg, 500 mg, 400 mg, 300 mg, 250 mg, 225 mg, 200 mg, 175 mg, 150 mg, 125 mg, 100 mg, 90 mg, 80 mg, 75 mg, 60 mg, 55 mg, or 50 mg. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, vilazodone, or a pharmaceutically acceptable salt thereof. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone. In some embodiments, the API is a pharmaceutically acceptable salt of abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone. In some embodiments, the API is a lipophilic API. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the log P of the lipophilic API is 2.0 or higher. In some embodiments, the log P of the lipophilic API is 3.0 or higher. In some embodiments, the amorphous solids dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solids dispersion described herein further comprises one or more adsorbents. In some embodiments, the amorphous solids dispersion described herein further comprises one or more other additives. In some embodiments, other additives include organic and inorganic acids. In some embodiments, other additives include antioxidants.

[0132] This document discloses pharmaceutical compositions comprising an API. In some embodiments, the pharmaceutical composition is formulated in a unit dosage form such as a capsule or tablet. In some embodiments, the API is present in the pharmaceutical composition in an amount from 10 mg to 1000 mg. In some embodiments, the API is present in an amount from 20 mg to 500 mg. In some embodiments, the API is present in an amount from 20 mg to 400 mg. In some embodiments, the API is present in an amount from 20 mg to 300 mg. In some embodiments, the API is present in an amount from 25 mg to 250 mg. In some embodiments, the API is present in an amount from 30 mg to 200 mg. In some embodiments, the API is present in an amount from about 50 mg, about 100 mg, or about 150 mg. In some embodiments, the API is present in an amount from 50 mg, 100 mg, or 150 mg. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, vilazorone, or a pharmaceutically acceptable salt thereof. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, or vilazodone. In some embodiments, the API is a pharmaceutically acceptable salt of abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, or vilazodone. In some embodiments, the API is a lipophilic API. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the lipophilic API has a log P of 2.0 or higher. In some embodiments, the amorphous solids dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solids dispersion described herein further comprises one or more adsorbents. In some embodiments, the amorphous solids dispersion described herein further comprises one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0133] In some embodiments, a pharmaceutical composition is provided comprising an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, and vilazorone, or pharmaceutically acceptable salts thereof, present in doses from about 1.0 mg to about 1000 mg, wherein the doses include, but are not limited to, about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0 mg, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, etc. g, 14.0mg, 14.5mg, 15.0mg, 15.5mg, 16mg, 16.5mg, 17mg, 17.5mg, 18mg, 18.5mg, 19mg, 19.5mg, 20mg, 20.5mg, 21mg, 21.5mg, 22mg, 22.5mg, 23mg, 23.5m g, 24mg, 24.5mg, 25mg, 25.5mg, 26mg, 26.5mg, 27mg, 27.5mg, 28mg, 28.5mg, 29mg, 29.5mg, 30mg, 30.5mg, 31mg, 31.5mg, 32mg, 32.5mg, 33mg, 33.5mg, 36 mg, 36.5mg, 37mg, 37.5mg, 38mg, 38.5mg, 39mg, 39.5mg, 40mg, 40.5mg, 41mg, 41.5mg, 42mg, 42.5mg, 43mg, 43.5mg, 44mg, 44.5mg, 45mg, 45.5mg, 46mg, 4 6.5mg, 47mg, 47.5mg, 48mg, 48.5mg, 49mg, 49.5mg, 50mg, 55mg, 60mg, 65mg, 70mg, 75mg, 80mg, 85mg, 90mg, 95mg, 100mg, 105mg, 110mg, 115mg, 120mg, 12 5mg, 130mg, 135mg, 140mg, 145mg, 150mg, 155mg, 160mg, 165mg, 170mg, 175mg, 180mg, 185mg, 190mg, 200mg, 205mg, 210mg, 215mg, 220mg, 225mg, 230mg, 235mg, 240mg, 245mg, 250mg, 255mg, 260mg, 265mg, 270mg, 275mg, 280mg, 285mg, 290mg, 295mg, 300mg, 305mg, 310mg, 315mg, 320mg, 325mg, 326mg, 326.5mg, 327mg, 327.5mg, 328mg, 328.5mg, 329mg, 329.5mg, 330mg, 330.5mg, 331mg, 331.5mg, 332mg, 332.5mg, 333mg, 333.5mg, 334mg, 334.5mg, 335mg, 33 5.5mg, 336mg, 336.5mg, 337mg, 337.5mg, 338mg, 338.5mg, 339mg, 339.5mg, 340mg, 340.5mg, 341mg, 341.5mg, 342mg, 342.5mg, 343mg, 343.5mg, 344mg 344.5mg、345mg、345.5mg、346mg、346.5mg、347mg、347.5mg、348mg、348.5m g、349mg、349.5mg、350mg、350.5mg、351mg、351.5mg、352mg、352.5mg、353m g、353.5mg、354mg、354.5mg、355mg、355.5mg、356mg、356.5mg、357mg、357. 5mg、358mg、358.5mg、359mg、359.5mg、360mg、360.5mg、361mg、361.5mg、362 mg、362.5mg、363mg、363.5mg、364mg、364.5mg、365mg、365.5mg、366mg、366 .5mg、367mg、367.5mg、368mg、369.5mg、370mg、370.5mg、371mg、371.5mg、3 72mg, 372.5mg, 373mg, 373.5mg, 374mg, 374.5mg, 375mg, 375.5mg, 376mg, 376.5mg, 377mg, 377.5mg, 378mg, 378.5mg, 379mg, 379.5mg, 380mg, 380.5mg 、381mg、381.5mg、382mg、382.5mg、383mg、383.5mg、384mg、384.5mg、385mg 、385.5mg、386mg、386.5mg、387mg、387.5mg、388mg、388.5mg、389mg、389.5 mg、390mg、390.5mg、391mg、391.5mg、392mg、392.5mg、393mg、393.5mg、394 mg、394.5mg、395mg、395.5mg、396mg、396.5mg、397mg、397.5mg、398mg、398.5mg, 399mg, 399.5mg, 400mg, 405mg, 410mg, 415mg, 420mg, 425mg, 430mg, 435mg, 440mg, 445mg, 450mg, 455mg, 46 0mg, 465mg, 470mg, 475mg, 480mg, 485mg, 490mg, 495mg, 500mg, 505mg, 510mg, 515mg, 520mg, 525mg, 530mg, 535m g, 540mg, 545mg, 550mg, 555mg, 560mg, 565mg, 570mg, 575mg, 580mg, 585mg, 590mg, 595mg, 600mg, 605mg, 610mg, 615mg, 620mg, 625mg, 630mg, 635mg, 640mg, 645mg, 650mg, 655mg, 660mg, 665mg, 675mg, 680mg, 685mg, 690mg, 695 mg, 700mg, 705mg, 710mg, 715mg, 720mg, 725mg, 730mg, 735mg, 740mg, 745mg, 750mg, 755mg, 760mg, 765mg, 770mg , 775mg, 780mg, 785mg, 790mg, 795mg, 800mg, 805mg, 810mg, 815mg, 820mg, 825mg, 830mg, 835mg, 840mg, 845mg, 85 0 mg, 855 mg, 860 mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg, or 1000 mg. In some embodiments, the pharmaceutical composition is formulated in unit dosage forms such as capsules or tablets. In some embodiments, the pharmaceutical composition is an ASD. In some embodiments, the ASD comprises an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, and vilazorone, or a pharmaceutically acceptable salt thereof, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solid dispersions described herein further comprise one or more adsorbents. In some embodiments, the amorphous solid dispersions described herein further comprise one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0134] In some embodiments, the ASD comprises about 1 mg to about 500 mg of API. In some embodiments, the ASD comprises about 10 mg to about 400 mg of API. In some embodiments, the ASD comprises about 25 mg to about 200 mg of API. In some embodiments, the ASD comprises about 50 mg to about 150 mg of API. In some embodiments, the ASD comprises about 75 mg to about 125 mg of API. In some embodiments, the ASD comprises about 75 mg to about 100 mg of API. In some embodiments, the ASD comprises about 100 mg to about 125 mg of API. In some embodiments, the ASD is formulated as part of a pharmaceutical composition in a unit dosage form such as capsules or tablets. In some embodiments, the API is selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, and vilazorone, or pharmaceutically acceptable salts thereof. In some embodiments, the API is a lipophilic API. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the log P of the lipophilic API is 2.0 or higher. In some embodiments, the amorphous solids dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solids dispersion described herein further comprises one or more adsorbents. In some embodiments, the amorphous solids dispersion described herein further comprises one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0135] In some embodiments, the API comprises about 5%, 10%, 15%, 20%, 25%, 30%, 40%, or 50% of the total weight of the composition. In some embodiments, the API is present in an amount from about 5% to about 70% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is present in an amount from about 10% to about 60% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is present in an amount from about 10% to about 20% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is present in an amount from about 15% to about 25% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is present in an amount from about 20% to about 30% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is present in an amount from about 25% to about 40% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is present in an amount from about 40% to about 50% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is present in an amount from about 50% to about 70% of the total weight of the ASD or pharmaceutical composition described herein. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, vilazodone, or a pharmaceutically acceptable salt thereof. In some embodiments, the API is a lipophilic API. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, vilazodone, or a pharmaceutically acceptable salt thereof. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the lipophilic API has a log P of 2.0 or higher. In some embodiments, the amorphous solids dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solids dispersion described herein further comprises one or more adsorbents. In some embodiments, the amorphous solids dispersion described herein further comprises one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0136] In some embodiments, the API is present in the ASD in an amount of about 0.1% by weight to about 99% by weight. In some embodiments, the API is present in amounts of about 0.1% to about 1%, about 0.1% to about 10%, about 0.1% to about 20%, about 0.1% to about 30%, about 0.1% to about 40%, about 0.1% to about 50%, about 0.1% to about 60%, about 0.1% to about 70%, about 0.1% to about 80%, about 0.1% to about 90%, about 0.1% to about 99%, about 1% to about 10%, about 1% to about 20%, about 1% to about 30%, about 1% to about 40%, about 1 % to 50%, about 1% to 60%, about 1% to 70%, about 1% to 80%, about 1% to 90%, about 1% to 99%, about 10% to 20%, about 10% to 30%, about 10% to 40%, about 10% to 50%, about 10% to 60%, about 10% to 70%, about 10% to 80%, about 10% to 90%, about 10% to 99%, about 20% to 30%, about 20% to 40%, about 20% to 50% %, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 20% to about 99%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to about 99%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 90% The API is present in ASD in amounts of about 40% to about 99%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 90%, about 50% to about 99%, about 60% to about 70%, about 60% to about 80%, about 60% to about 90%, about 60% to about 99%, about 70% to about 80%, about 70% to about 90%, about 70% to about 99%, about 80% to about 90%, about 80% to about 99%, or about 90% to about 99% by weight. In some embodiments, the API is present in ASD in amounts of about 0.1%, about 1%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 99% by weight. In some embodiments, the API is present in the ASD in an amount of at least about 0.1 wt%, about 1 wt%, about 10 wt%, about 20 wt%, about 30 wt%, about 40 wt%, about 50 wt%, about 60 wt%, about 70 wt%, about 80 wt%, or about 90 wt%. In some embodiments, the API is present in the ASD in an amount of at most about 1 wt%, about 10 wt%, about 20 wt%, about 30 wt%, about 40 wt%, about 50 wt%, about 60 wt%, about 70 wt%, about 80 wt%, about 90 wt%, or about 99 wt%.In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, vilazorone, or a pharmaceutically acceptable salt thereof. In some embodiments, the API is a lipophilic API. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the lipophilic API has a log P of 2.0 or higher. In some embodiments, the amorphous solids dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solids dispersion described herein further comprises one or more adsorbents. In some embodiments, the amorphous solids dispersion described herein further comprises one or more other additives. In some embodiments, the other additives comprise organic and inorganic acids. In some embodiments, the other additives comprise antioxidants.

[0137] In some embodiments, this document describes an amorphous solid dispersion comprising an API such as abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, or vilazodone, or a pharmaceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion is characterized by providing an amorphous powder X-ray diffraction pattern. In some embodiments, an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, and vilazodone, or a pharmaceutically acceptable salt thereof, is present in the amorphous solid dispersion in an amount from about 5 wt% to about 70 wt% on a solids basis. In some embodiments, an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, and vilazodone, or a pharmaceutically acceptable salt thereof, is present in the amorphous solid dispersion in an amount from about 5 wt% to about 60 wt% on a solids basis. In some embodiments, an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, and vilazodone, or a pharmaceutically acceptable salt thereof, is present in an amorphous solid dispersion in an amount of about 10 wt% to about 50 wt% on a solid basis. In some embodiments, an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, and vilazodone, or a pharmaceutically acceptable salt thereof, is present in an amorphous solid dispersion in an amount of about 20 wt% to about 40 wt% on a solid basis. In some embodiments, an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, and vilazodone, or a pharmaceutically acceptable salt thereof, is present in an amorphous solid dispersion in an amount of about 5 wt% to about 30 wt% on a solid basis.

[0138] In some embodiments, the amorphous solid dispersions described herein comprise surfactants. In some embodiments, the surfactant is selected from polymeric surfactants and phospholipids. In some embodiments, the surfactant is a polymeric nonionic surfactant. In some embodiments, the surfactant is a polymeric ionic surfactant. In some embodiments, the surfactant comprises a block copolymer of polyethylene glycol and polypropylene glycol. In some embodiments, the surfactant comprises phospholipids or derivatives thereof. In some embodiments, the surfactant comprises lecithin. In some embodiments, the surfactant comprises a polyvinylcaprolactam-based graft copolymer (PVAc-PVCap-PEG). In some embodiments, the surfactant comprises lecithin. In some embodiments, the surfactant comprises polyoxyethylene hydrogenated castor oil. In some embodiments, the surfactant comprises PEG. In some embodiments, the surfactant comprises polyoxyethylene glycerol esters. In some embodiments, the surfactant comprises TPGS. In some embodiments, the surfactant comprises SLS. In some embodiments, the surfactant comprises polysorbate esters. In some embodiments, the polymeric nonionic surfactant has a number-average molecular weight of about 7,000 to about 10,000 Da. In some embodiments, the amorphous solid dispersions described herein comprise surfactants. In some embodiments, the amorphous solid dispersions described herein comprise surfactants, the surfactant comprising one or more phospholipids. In some embodiments, the surfactant comprises one or more of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatal acetal, sphingomyelin, and phosphatidic acid. In some embodiments, the one or more phospholipids comprise greater than 50 wt%, 60 wt%, 70 wt%, 80 wt%, or 90 wt% phosphatidylcholine. In some embodiments, the surfactant comprises lecithin. In some embodiments, the surfactant is present in the amorphous solids dispersion in an amount of about 5 wt% to about 70 wt% based on solids. In some embodiments, the surfactant is present in the amorphous solids dispersion in an amount of about 20 wt% to about 60 wt% based on solids. In some embodiments, the surfactant is present in the amorphous solids dispersion in an amount of about 10 wt% to about 30 wt% based on solids. In some embodiments, the weight ratio of an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, and vilazorone, or a pharmaceutically acceptable salt thereof, to the surfactant is in any range from about 10:1 to about 1:10 or between. In some embodiments, the API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, and vilazorone, or pharmaceutically acceptable salts thereof, is in a weight ratio of about 5:1 to about 1:4 to the surfactant.In some embodiments, the weight ratio of an API selected from abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, and vilazorone, or pharmaceutically acceptable salts thereof, to a surfactant is about 2:1 to about 1:2. In some embodiments, the weight ratio of the API free base or a pharmaceutically acceptable salt thereof to a surfactant is about 1:1 to about 1:2. In some embodiments, the weight ratio of the API free base or a pharmaceutically acceptable salt thereof to a surfactant is about 0.5:1 to about 1:3. In some embodiments, the weight ratio of the API free base or a pharmaceutically acceptable salt thereof to a surfactant is about 1:1 to about 1:3.

[0139] In some embodiments, the ASD comprises: i) a free base of an API, such as abiraterone acetate, alectinib, pazopanib, cabozantinib, venetoc, lurasidone, or vilazorone, or a pharmaceutically acceptable salt thereof; ii) a surfactant; and iii) a hydrophilic polymer. In some embodiments, the ASD is formulated in unit dosage forms such as capsules or tablets. In some embodiments, the free base of an API or a pharmaceutically acceptable salt thereof is present in the ASD in an amount of about 10 mg to about 500 mg. In some embodiments, the free base of an API or a pharmaceutically acceptable salt thereof is present in the ASD in an amount of about 20 mg to about 200 mg. In some embodiments, the free base of an API or a pharmaceutically acceptable salt thereof is present in the ASD in an amount of about 25 mg, about 50 mg, about 100 mg, about 150 mg, or about 200 mg. In some embodiments, the surfactant is present in the ASD in an amount of about 10 mg to about 500 mg. In some embodiments, the surfactant is present in the ASD in an amount of about 20 mg to about 200 mg. In some embodiments, the hydrophilic polymer is present in ASD in an amount of about 10 mg to about 500 mg. In some embodiments, the hydrophilic polymer is present in ASD in an amount of about 20 mg to about 200 mg.

[0140] In some embodiments, the amorphous solid dispersions described herein comprise hydrophilic polymers. In some embodiments, the amorphous solid dispersions described herein comprise nonionic or ionic hydrophilic polymers. In some embodiments, the hydrophilic polymer comprises an enteric polymer. In some embodiments, the enteric polymer comprises a methacrylate copolymer, hydroxypropyl methylcellulose acetate succinate, or cellulose acetate phthalate. In some embodiments, the hydrophilic polymer comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol (e.g., sold under the trade names Poloxamer or Pluronic F-68), sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters (e.g., capryloyl hexanoyl polyoxyethylene-8 glycerol ester sold under the trade name Labrasol; lauroyl polyoxyethylene-32 glycerol ester sold under the trade name Gelucire), polysorbate, or combinations thereof. In some embodiments, the hydrophilic polymer comprises polyvinyl alcohol (PVA), oligosaccharides, polysaccharides, polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC or hydroxypropyl methylcellulose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyethylene glycol (PEG), a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PCL-PVAc-PEG, also known as...) The nonionic hydrophilic polymer is polyethylene oxide, cyclodextrin (CD), and its derivatives, such as hydroxypropyl β-cyclodextrin (HP-β-CD), polymethyl methacrylate (e.g., Eudragit), or combinations thereof. In some embodiments, the nonionic hydrophilic polymer is HPMC, PVP, HP-β-CD, or PVA. In some embodiments, the ionic hydrophilic polymer is sulfobutyl ether-β-cyclodextrin. In some embodiments, the hydrophilic polymer comprises polymethyl methacrylate (e.g., Eudragit). In some embodiments, the hydrophilic polymer comprises polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol.

[0141] In some embodiments, the pharmaceutical compositions described herein are free of organic acids. In some embodiments, ASD is free of organic acids. In some embodiments, the pharmaceutical compositions are free of any acids. In some embodiments, ASD is free of any acids.

[0142] The formation of an amorphous solid dispersion can produce a certain particle size of ASD. In some embodiments, the particle size of ASD is from about 1 nm to 1 mm. In some embodiments, the particle size of ASD is from about 0.01 to 1000 micrometers. In some embodiments, the particle size of ASD is from about 0.01 micrometers to about 1000 micrometers. In some embodiments, the particle size of ASD is at least about 0.01 micrometers. In some embodiments, the particle size of ASD is at most about 1000 micrometers. In some embodiments, the particle size of ASD is from about 1 micrometer to about 50 micrometers. In some embodiments, the particle size of ASD is at least about 1 micrometer. In some embodiments, the particle size of ASD is at most about 50 micrometers. In some embodiments, the particle size of ASD is from about 10 micrometers to about 15 micrometers. In some embodiments, the particle size of ASD is about 1 micrometer to about 3 micrometers, about 1 micrometer to about 7 micrometers, about 1 micrometer to about 10 micrometers, about 1 micrometer to about 13 micrometers, about 1 micrometer to about 17 micrometers, about 1 micrometer to about 20 micrometers, about 1 micrometer to about 23 micrometers, about 1 micrometer to about 27 micrometers, about 1 micrometer to about 30 micrometers, about 1 micrometer to about 40 micrometers, about 1 micrometer to about 50 micrometers, about 10 micrometers to about 13 micrometers, about 10 micrometers to about 17 micrometers, about 10 micrometers to about 20 micrometers, about 10 micrometers to about 23 micrometers, about 10 micrometers to about 27 micrometers, about 10 micrometers to about 30 micrometers, about 10 micrometers to about 40 micrometers, about 10 micrometers to about 50 micrometers, about 20 micrometers to about 27 micrometers, about 20 micrometers to about 30 micrometers, about 20 micrometers to about 40 micrometers, about 20 micrometers to about 50 micrometers, about 30 micrometers to about 40 micrometers, about 30 micrometers to about 50 micrometers, or about 40 micrometers to about 50 micrometers. In some embodiments, the particle size of ASD is about 1 micrometer to about 100 micrometers. In some embodiments, the granularity of ASD is at least about 1 micrometer. In some embodiments, the granularity of ASD is about 0.1, 1, 3, 5, 7, 10, 13, 17, 20, 23, 25, 27, 30, 33, 35, 37, 40, 43, 45, 47, 50, 60, 70, 80, 90, or 100 micrometers or less. In some embodiments, the granularity of ASD is about 20 micrometers or less.

[0143] In some embodiments, a particle size distribution of an amorphous solid dispersion is obtained. In some embodiments, the terms D10, D50, and D90 are used to describe the particle size distribution. In some embodiments, the D90 particle size of ASD is equal to or less than about 1,000 μm, 950 μm, 900 μm, 800 μm, 700 μm, 600 μm, 500 μm, 400 μm, 300 μm, 200 μm, 100 μm, 75 μm, 65 μm, 50 μm, 25 μm, 20 μm, 15 μm, or 10 μm. In some embodiments, the D50 particle size of ASD is equal to or less than about 500 μm, 400 μm, 300 μm, 200 μm, 100 μm, 50 μm, 35 μm, 25 μm, 20 μm, 15 μm, 10 μm, or 5 μm. In some embodiments, the D10 particle size of ASD is equal to or less than about 200 μm, 100 μm, 50 μm, 45 μm, 40 μm, 35 μm, 30 μm, 25 μm, 20 μm, 15 μm, 10 μm, 9 μm, 8 μm, 7 μm, 6 μm, 5 μm, 4 μm, 3 μm, 2 μm or 1 μm.

[0144] In some embodiments, a particle size distribution of an amorphous solid dispersion is obtained. In some embodiments, the terms D10, D50, and D90 are used to describe the particle size distribution. In some embodiments, the D90 particle size of ASD is from about 10 μm to about 1,000 μm. In some embodiments, the D90 particle size of ASD is about 10 μm to about 20 μm, about 10 μm to about 30 μm, about 10 μm to about 50 μm, about 10 μm to about 100 μm, about 10 μm to about 150 μm, about 10 μm to about 200 μm, about 10 μm to about 500 μm, about 10 μm to about 750 μm, about 10 μm to about 1,000 μm, about 20 μm to about 30 μm, about 20 μm to about 50 μm, about 20 μm to about 100 μm, about 20 μm to about 150 μm, about 20 μm to about 200 μm, about 50 μm to about 100 μm, about 100 μm to about 1,000 μm, about 500 μm to about 1,000 μm, or about 750 μm to about 1,000 μm. In some embodiments, the D90 particle size is at least about 10 μm, about 20 μm, about 30 μm, about 50 μm, about 100 μm, about 150 μm, about 200 μm, about 500 μm, or about 750 μm. In some embodiments, the D90 particle size is at most about 15 μm. In some embodiments, the D90 particle size is at most about 10 μm, 15 μm, 20 μm, about 30 μm, about 50 μm, about 100 μm, about 150 μm, about 200 μm, about 500 μm, or about 1,000 μm.

[0145] In some embodiments, a particle size distribution of an amorphous solid dispersion is obtained. In some embodiments, the terms D10, D50, and D90 are used to describe the particle size distribution. In some embodiments, the D50 value of ASD is from about 1 μm to about 100 μm. In some embodiments, the D50 value of ASD is from about 10 μm to about 15 μm. In some embodiments, the D50 particle size is from about 5 μm to about 10 μm, from about 5 μm to about 15 μm, from about 5 μm to about 20 μm, from about 5 μm to about 25 μm, from about 5 μm to about 30 μm, from about 5 μm to about 40 μm, from about 5 μm to about 50 μm, from about 5 μm to about 60 μm, from about 5 μm to about 75 μm, from about 5 μm to about 100 μm, from about 10 μm to about 15 μm, from about 10 ... μm to about 20μm, about 10μm to about 25μm, about 10μm to about 30μm, about 10μm to about 40μm, about 10μm to about 50μm, about 10μm to about 60μm, about 10μm to about 75μm, about 10μm to about 100μm, about 15μm to about 20μm, about 15μm to about 25μm, about 15μm to about 30μm, about 15μm to about 40μm Approximately 15μm to approximately 50μm, approximately 15μm to approximately 60μm, approximately 15μm to approximately 75μm, approximately 15μm to approximately 100μm, approximately 20μm to approximately 25μm, approximately 20μm to approximately 30μm, approximately 20μm to approximately 40μm, approximately 20μm to approximately 50μm, approximately 20μm to approximately 60μm, approximately 20μm to approximately 75μm, approximately 20μm to approximately 100μm, approximately 25μm to The particle size can be approximately 30 μm, approximately 25 μm to approximately 40 μm, approximately 25 μm to approximately 50 μm, approximately 25 μm to approximately 60 μm, approximately 25 μm to approximately 75 μm, approximately 25 μm to approximately 100 μm, approximately 30 μm to approximately 40 μm, approximately 30 μm to approximately 50 μm, approximately 30 μm to approximately 60 μm, approximately 30 μm to approximately 75 μm, approximately 50 μm to approximately 100 μm, or approximately 75 μm to approximately 100 μm. In some embodiments, the D50 particle size is approximately 5 μm, approximately 10 μm, approximately 15 μm, approximately 20 μm, approximately 25 μm, approximately 30 μm, approximately 40 μm, approximately 50 μm, approximately 60 μm, approximately 75 μm, or approximately 100 μm. In some embodiments, the D50 particle size is at least approximately 0.5 μm, 5 μm, approximately 10 μm, approximately 15 μm, or approximately 20 μm. In some embodiments, the D50 particle size is up to about 10 μm, about 15 μm, about 20 μm, about 25 μm, about 30 μm, about 40 μm, about 50 μm, about 60 μm, about 75 μm, or about 100 μm.

[0146] In some embodiments, a particle size distribution of an amorphous solid dispersion is obtained. In some embodiments, the terms D10, D50, and D90 are used to describe the particle size distribution. In some embodiments, the D10 value of ASD is from about 0.1 μm to about 50 μm. In some embodiments, the D10 particle size is about 0.1 μm to about 1 μm, about 0.1 μm to about 2 μm, about 0.1 μm to about 3 μm, about 0.1 μm to about 4 μm, about 0.1 μm to about 5 μm, about 0.1 μm to about 7 μm, about 0.1 μm to about 10 μm, about 0.1 μm to about 20 μm, about 0.1 μm to about 30 μm, about 0.1 μm to about 40 μm, about 0.1 μm to about 50 μm, about 1 μm to about 2 μm, about 1 μm to about 3 μm, about 1 μm to about 4 μm, about 1 μm to about 5 μm, about 1 μm to about 7 μm, about 1 μm to about 10 μm, about 1 μm to about 20 μm, or about 1 μm to about 50 μm. In some embodiments, the D10 particle size is about 0.1 μm, about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 7 μm, about 10 μm, about 20 μm, about 30 μm, about 40 μm, or about 50 μm. In some embodiments, the D10 particle size is at least about 0.1 μm, about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 7 μm, about 10 μm, about 20 μm, about 30 μm, or about 40 μm. In some embodiments, the D10 particle size is at most about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 7 μm, about 10 μm, about 20 μm, about 30 μm, about 40 μm, or about 50 μm.

[0147] a) Cabozantinib

[0148] On one hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API, a surfactant, a hydrophilic polymer, and optionally an adsorbent. On the other hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API. In some embodiments, the API is a free base of cabozantinib or a pharmaceutically acceptable salt thereof. In some embodiments, the API is cabozantinib malate.

[0149] In some embodiments, ASD comprises cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 3% by weight to about 60% by weight of ASD. In some embodiments, ASD comprises cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 30% by weight of ASD. In some embodiments, ASD comprises cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 12% by weight to about 25% by weight of ASD. In some embodiments, ASD comprises cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 15% by weight of ASD. In some embodiments, ASD comprises cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is about 15% by weight of ASD. In some embodiments, the ASD comprises a free base of cabozantinib or a pharmaceutically acceptable salt thereof, wherein the amount of the free base of cabozantinib or a pharmaceutically acceptable salt thereof is approximately 20% by weight of the ASD. In some embodiments, the API comprises cabozantinib malate.

[0150] In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 5% to about 60%. In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 10% to about 50%. In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 15% to about 30%. In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 25% to about 40%. In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in amounts of about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 5% to about 35%, about 5% to about 40%, about 5% to about 45%, about 5% to about 50%, about 5% to about 55%, about 5% to about 60%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%. %, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% The amorphous solids are present in the dispersion at a weight percentage of about 60%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 50% to about 55%, about 50% to about 60%, or about 55% to about 60%.In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion at a weight percentage of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion at a weight percentage of at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or about 55%. In some embodiments, the free base of cabozantinib or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion in weight percentages of up to about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, the salt of cabozantinib is cabozantinib malate.

[0151] In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is nonionic. In some embodiments, the hydrophilic polymer is ionic. In some embodiments, the hydrophilic polymer is an enteric polymer. In some embodiments, the pharmaceutical composition described herein comprises ASD, which comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is HPMC (such as HPMC-E5), copovidone, polymethacrylate, or a combination thereof. In some embodiments, the hydrophilic polymer comprises copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, HPMC, HPMCS, or a combination thereof. In some embodiments, the hydrophilic polymer comprises copovidone. In some embodiments, the hydrophilic polymer comprises polymethacrylate (e.g., Eudragit). In some embodiments, the hydrophilic polymer comprises a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam. In some embodiments, the hydrophilic polymer comprises HPMC. In some embodiments, the hydrophilic polymer is present in an amount from about 1% by weight to about 80% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 5% to about 70% by weight of ASD.

[0152] In some embodiments, ASD comprises an adsorbent. In some embodiments, the adsorbent is silica. In some embodiments, the adsorbent is present in an amount of about 1% by weight to about 40% by weight of ASD.

[0153] In some embodiments, the ASD optionally includes a surfactant. In some embodiments, the surfactant includes phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters, polysorbate esters, or combinations thereof. In some embodiments, the surfactant includes lecithin and TPGS. In some embodiments, the surfactant includes lecithin. In some embodiments, the surfactant includes PEG. In some embodiments, the surfactant includes block copolymers of polyethylene glycol and polypropylene glycol. In some embodiments, the surfactant includes SLS. In some embodiments, the surfactant includes graft copolymers based on polyvinyl acetate and polyvinylcaprolactam. In some embodiments, the surfactant includes polyoxyethylene hydrogenated castor oil (e.g., sold under the trade name RH40). In some embodiments, the surfactant includes polysorbate esters. In some embodiments, the surfactant includes polyoxyethylene glycerol esters (e.g., Labrasol or Gelucire). In some embodiments, the surfactant includes TPGS. In some embodiments, the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene glycerol esters (e.g., Labrasol or Gelucire), polyoxyethylene hydrogenated castor oil, or combinations thereof. In some embodiments, the surfactant is present in an amount of about 5% by weight to about 60% by weight of the ASD. In some embodiments, the surfactant is present in an amount of about 10% by weight to about 55% by weight of the ASD.

[0154] In some embodiments, ASD optionally contains an inorganic acid or an organic acid. In some embodiments, ASD optionally contains an organic acid. In some embodiments, the organic acid is malic acid. In some embodiments, ASD contains an organic acid, wherein the organic acid is malic acid. In some embodiments, the inorganic acid or organic acid is present in an amount of about 1% by weight to about 40% by weight of ASD.

[0155] In some embodiments, ASD comprises a free base of cabozantinib or a pharmaceutically acceptable salt thereof, wherein the amount of the free base of cabozantinib or a pharmaceutically acceptable salt thereof is from about 10% to about 30% by weight of ASD. In some embodiments, ASD comprises a surfactant, wherein the amount of the surfactant is from about 10% to about 55% by weight of ASD. In some embodiments, the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, a graft copolymer based on polyvinylcaprolactam (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, TPGS, or a combination thereof. In some embodiments, ASD comprises a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 5% to about 70% by weight of ASD. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, ASD optionally comprises an adsorbent, wherein the amount of the adsorbent is from about 5% to 40% by weight of ASD. In some embodiments, the adsorbent is silica. In some embodiments, ASD comprises an organic acid, wherein the amount of the organic acid is from about 5% to 40% by weight of ASD. In some embodiments, the organic acid is malic acid.

[0156] In some embodiments, the amount of ASD comprising cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 12% to about 25% by weight of the ASD. In some embodiments, the ASD comprises a surfactant in an amount from about 15% to about 50% by weight of the ASD. In some embodiments, the surfactant comprises lecithin, TPGS, or a combination thereof. In some embodiments, the ASD comprises a hydrophilic polymer in an amount from about 10% to about 50% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the ASD optionally comprises an adsorbent in an amount from about 15% to 30% by weight of the ASD. In some embodiments, the adsorbent is silica. In some embodiments, the ASD optionally comprises an organic acid in an amount from about 10% to 30% by weight of the ASD. In some embodiments, the organic acid is malic acid.

[0157] In some embodiments, the pharmaceutical compositions described herein comprise ASD, the ASD comprising a free base of cabozantinib or a pharmaceutically acceptable salt thereof (such as cabozantinib malate), the free base of cabozantinib or a pharmaceutically acceptable salt thereof comprising about 15% by weight of the ASD. In some embodiments, the ASD comprises a surfactant comprising about 45% by weight of the ASD. In some embodiments, the surfactant comprises lecithin and TPGS. In some embodiments, the ASD comprises a hydrophilic polymer comprising about 15% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the ASD optionally comprises an adsorbent comprising about 23% by weight of the ASD. In some embodiments, the adsorbent is silica.

[0158] In some embodiments, the pharmaceutical compositions described herein comprise ASD, which comprises cabozantinib free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 55% by weight of ASD. In some embodiments, the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 12% by weight to about 25% by weight of ASD. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of surfactant is from about 10% by weight to about 55% by weight of ASD. In some embodiments, the amount of surfactant is from about 15% by weight to about 50% by weight of ASD. In some embodiments, the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene glycerol ester, polyoxyethylene hydrogenated castor oil, or combinations thereof. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of hydrophilic polymer is from about 5% by weight to about 70% by weight of ASD. In some embodiments, the amount of hydrophilic polymer is from about 10% by weight to about 50% by weight of ASD. In some embodiments, the amount of the hydrophilic polymer is about 15% to 30% by weight of the ASD. In some embodiments, the hydrophilic polymer is copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, HPMC, HPMCAS, or a combination thereof. In some embodiments, the ASD contains an adsorbent. In some embodiments, the amount of the adsorbent is about 5% to 40% by weight of the ASD. In some embodiments, the adsorbent is silica. In some embodiments, the ASD contains an acid such as an organic acid. In some embodiments, the amount of the organic acid is about 5% to 40% by weight of the ASD. In some embodiments, the amount of the organic acid is about 10% to 30% by weight of the ASD. In some embodiments, the organic acid is malic acid.

[0159] In some embodiments, the pharmaceutical composition described herein comprises an ASD containing cabozantinib free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is about 10-30% by weight of the ASD. In some embodiments, the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is about 10-28% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is about 10% by weight to about 60% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 15% by weight to about 40% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 10% by weight of the ASD. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the hydrophilic polymer is L100-55. In some embodiments, the hydrophilic polymer is HPMC-E5. In some embodiments, the hydrophilic polymer is HPMC-LF. In some embodiments, the hydrophilic polymer is soluplus. In some embodiments, the hydrophilic polymer is VA64, L100-55, VA64, HPMC-E5, HPMC-LF, or any combination thereof. In some embodiments, the ASD contains a surfactant. In some embodiments, the amount of the surfactant is from about 10% to about 40% by weight of the ASD. In some embodiments, the amount of the surfactant is from about 15% to about 40% by weight of the ASD. In some embodiments, the amount of the surfactant is from about 20% to about 25% by weight of the ASD. In some embodiments, the surfactant is TPGS. In some embodiments, the amount of TPGS is from about 15-30% by weight of the ASD. In some embodiments, the surfactant is lecithin. In some embodiments, lecithin is present in an amount of about 19% by weight of the ASD. In some embodiments, the ASD contains an organic acid. In some embodiments, the organic acid is malic acid. In some embodiments, malic acid is present in an amount of from about 10% to about 20% by weight of the ASD. In some embodiments, the ASD contains an adsorbent. In some embodiments, the adsorbent is present in an amount of from about 15% to about 30% by weight of the ASD. In some embodiments, the adsorbent is SiO2. In some embodiments, SiO2 is present in an amount of about 15% to 40% by weight of ASD.

[0160] In some embodiments, the pharmaceutical composition described herein comprises an ASD comprising: a cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the cabozantinib free base or a pharmaceutically acceptable salt thereof is about 24% to 30% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is about 40% to 60% by weight of the ASD, and wherein the hydrophilic polymer is HPMCAS-LF or Soluplus; and a surfactant, wherein the surfactant is about 15% to about 25% by weight of the ASD, wherein the surfactant is TPGS.

[0161] In some embodiments, the pharmaceutical composition described herein comprises an ASD consisting of: a cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the cabozantinib free base or a pharmaceutically acceptable salt thereof is from about 20% to about 25% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 20% to about 40% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5; an organic acid, wherein the organic acid is present in an amount of from about 15% to 20% by weight of the ASD, and wherein the organic acid is malic acid; and an adsorbent, wherein the amount of the adsorbent is from about 20% by weight of the ASD, wherein the adsorbent is SiO2.

[0162] In some embodiments, the pharmaceutical composition described herein comprises an ASD consisting of: a cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the cabozantinib free base or a pharmaceutically acceptable salt thereof is about 24% to 27% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is about 9% to 10% by weight of the ASD, wherein the hydrophilic polymer is VA64, L100-55, or any combination thereof; a surfactant, wherein the amount of the surfactant is about 15% to 30% by weight of the ASD, wherein the surfactant is TPGS, lecithin, or any combination thereof; and an absorbent, wherein the amount of the absorbent is about 18-21% by weight of the ASD, wherein the absorbent is SiO2.

[0163] In some embodiments, the pharmaceutical composition described herein comprises an ASD consisting of: a cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the cabozantinib free base or a pharmaceutically acceptable salt thereof is about 20% to 25% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is about 18-20% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5; a surfactant, wherein the amount of the surfactant is about 18% to 20% by weight of the ASD, wherein the surfactant is TPGS; an organic acid, wherein the amount of the organic acid is about 18-20% by weight of the ASD, wherein the organic acid is malic acid; and an adsorbent, wherein the amount of the adsorbent is about 20% by weight of the ASD, wherein the adsorbent is SiO2.

[0164] In some embodiments, the pharmaceutical compositions comprising ASD described herein are formulated in unit dosage forms comprising cabozantinib free base or cabozantinib malate. In some embodiments, ASD comprises cabozantinib free base or a pharmaceutically acceptable salt thereof (such as cabozantinib malate) in an amount of about 20 mg to about 80 mg. In some embodiments, the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is about 20 mg to about 200 mg. In some embodiments, ASD comprises a surfactant in an amount of about 40 mg to about 220 mg. In some embodiments, ASD comprises a surfactant in an amount of about 20 mg to about 220 mg. In some embodiments, the surfactant is a phospholipid or a derivative thereof, such as lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, a graft copolymer based on polyvinylcaprolactam (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, TPGS, or a combination thereof. In some embodiments, the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene glycerol, polyoxyethylene hydrogenated castor oil, or a combination thereof. In some embodiments, the ASD comprises a hydrophilic polymer in an amount of about 40 mg to about 250 mg. In some embodiments, the ASD comprises a hydrophilic polymer in an amount of about 40 mg to about 150 mg. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the hydrophilic polymer is HPMC (such as HPMC-E5), copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, HPMCAS, or a combination thereof. In some embodiments, the ASD comprises an adsorbent in an amount of about 40 mg to about 200 mg. In some embodiments, the ASD optionally comprises an adsorbent in an amount of about 40 mg to about 120 mg. In some embodiments, the adsorbent is silica. In some embodiments, the ASD comprises an organic acid in an amount of about 20 mg to about 200 mg.

[0165] In some embodiments, the organic acid is malic acid.

[0166] In some embodiments, ASD comprises a free base of cabozantinib or a pharmaceutically acceptable salt thereof (such as cabozantinib malate), wherein the amount of the free base of cabozantinib or a pharmaceutically acceptable salt thereof is from about 20 mg to about 80 mg. In some embodiments, ASD comprises a surfactant, wherein the amount of the surfactant is from about 50 mg to about 200 mg. In some embodiments, the surfactant is lecithin. In some embodiments, ASD comprises a block copolymer of polyethylene glycol and polypropylene glycol, TPGS or a combination thereof, and a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 50 mg to about 130 mg. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, ASD comprises an adsorbent, wherein the amount of the adsorbent is from about 50 mg to about 100 mg. In some embodiments, the adsorbent is silica. In some embodiments, ASD comprises an organic acid, wherein the amount of the organic acid is from about 20 mg to about 70 mg. In some embodiments, the organic acid is malic acid.

[0167] In some embodiments, the pharmaceutical composition comprising an ASD has acceptable storage stability, wherein the ASD comprises cabozantinib free base or a pharmaceutically acceptable salt thereof (such as cabozantinib malate). In some embodiments, the pharmaceutical composition is chemically stable at 75°C / 75% RH for at least 2 weeks, wherein the API degradation of the storage-stable pharmaceutical composition is less than 5% at the end of the storage period. In some embodiments, the pharmaceutical composition is storage-stable at 40°C / 75% RH for at least 6 months, wherein the storage-stable pharmaceutical composition has less than 0.5% of any impurities at the end of the storage period. In some embodiments, the pharmaceutical composition is storage-stable at 25°C / 60% RH for at least 2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months, or 24 months, wherein the storage-stable pharmaceutical composition has less than 0.5% of any impurities at the end of the storage period.

[0168] In some embodiments, when administered orally, the AUC, AUC inf or AUC last When measured, the bioavailability of the pharmaceutical compositions described herein is superior to that of the corresponding reference compositions containing crystalline cabozantinib or its salts. In some embodiments, after oral administration under fasting conditions, C max or AUC last When measured, the bioavailability of the pharmaceutical composition is about 75% to about 200% of the bioavailability of a corresponding reference composition containing cabozantinib, wherein the reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, after oral administration under fasting conditions, C max or AUC lastWhen measured, the bioavailability of the pharmaceutical composition is about 100% to about 150% of the bioavailability of a corresponding reference composition containing cabozantinib, wherein the reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, after oral administration under fasting conditions, C max or AUC last When measured, the bioavailability of the pharmaceutical composition is about 150% to about 200% of the bioavailability of a corresponding reference composition containing cabozantinib, wherein the reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, when administered orally, the bioavailability is measured in AUC, AUCinf, or AUC. last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of corresponding compositions containing crystalline cabozantinib or its salts. In some embodiments, when administered orally, C max When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing crystalline cabozantinib or its salts. In some embodiments, when administered orally, the bioavailability is measured in AUC, AUCinf, or AUC. last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of C10 capsules containing cabozantinib or its salts. In some embodiments, when administered orally, C10 is used as a preservative. maxWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of COMETRIQ capsules containing cabozantinib or its salts. In some embodiments, the bioavailability exhibited by the pharmaceutical compositions is about 1.1 to about 10 times higher than that of COMETRIQ. In some embodiments, the bioavailability of the pharmaceutical composition is about 1.1 times to about 2 times, about 1.1 times to about 3 times, about 1.1 times to about 4 times, about 1.1 times to about 5 times, about 1.1 times to about 6 times, about 1.1 times to about 7 times, about 1.1 times to about 8 times, about 1.1 times to about 10 times, about 1.5 times to about 2 times, about 1.5 times to about 3 times, about 1.5 times to about 4 times, about 1.5 times to about 5 times, about 1.5 times to about 6 times, about 1.5 times to about 7 times, about 1.5 times to about 8 times, about 1.5 times to about 10 times, about 2 times to about 4 times, about 2 times Up to 5 times, about 2 times to 6 times, about 2 times to 7 times, about 2 times to 8 times, about 2 times to 10 times, about 3 times to 4 times, about 3 times to 5 times, about 3 times to 6 times, about 3 times to 7 times, about 3 times to 8 times, about 3 times to 10 times, about 4 times to 5 times, about 4 times to 6 times, about 4 times to 7 times, about 4 times to 8 times, about 4 times to 10 times, about 5 times to 6 times, about 5 times to 7 times, about 5 times to 8 times, about 5 times to 10 times, about 6 times to 7 times, about 6 times to 8 times, about 6 times to 10 times, about 7 times to 8 times, about 7 times to 10 times, or about 8 times to 10 times. In some embodiments, the pharmaceutical composition comprises an ASD, said ASD comprising cabozantinib or a pharmaceutically acceptable salt thereof (such as cabozantinib malate). In some embodiments, bioavailability is measured under feeding conditions. In some embodiments, bioavailability is measured under fasting conditions.

[0169] In some embodiments, when administered orally, the AUC, AUCinf, or AUC is measured. last Or C maxWhen measured, the bioavailability of the pharmaceutical compositions described herein is at least about 1.1 times, about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, or about 8 times higher than that of COMETRIQ. In some embodiments, the bioavailability of the pharmaceutical compositions is at least about 2 times higher than that of COMETRIQ. In some embodiments, the bioavailability of the pharmaceutical compositions is at least about 4 times higher than that of COMETRIQ. In some embodiments, the bioavailability of the pharmaceutical compositions is at most about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, or about 10 times higher than that of COMETRIQ. In some embodiments, bioavailability is measured in a canine model under fasting conditions. In some embodiments, bioavailability is measured in a canine model under feeding conditions. In some embodiments, AUC, AUCinf, or AUC is measured after oral administration. last When the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, when administered orally with C max During measurement, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 40%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 20%. In some embodiments, bioavailability is measured in a canine model. In some embodiments, the canine model is a beagle. In some embodiments, the pharmaceutical composition comprises an ASD comprising cabozantinib or a pharmaceutically acceptable salt thereof (such as cabozantinib malate). In some embodiments, bioavailability is measured under fed conditions. In some embodiments, bioavailability is measured under fasted conditions.

[0170] In some embodiments, salts of cabozantinib compounds are formed, for example, from a compound containing cabozantinib and a basic nitrogen atom as an acid addition salt (e.g., having an organic or inorganic acid), such as a pharmaceutically acceptable salt. Suitable inorganic acids are, for example, hydrohalic acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, for example, carboxylic acids, phosphonic acids, sulfonic acids or aminosulfonic acids, acetic acid, propionic acid, octanoic acid, decanoic acid, dodecanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, octanoic acid, azelaic acid, malic acid, tartaric acid, citric acid, amino acids such as glutamic acid or aspartic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, cyclohexanecarboxylic acid, adamantanecarboxylic acid, benzoic acid, salicylic acid, 4-aminosalicylic acid, phthalic acid, etc. Dicarboxylic acid, phenylacetic acid, mandelic acid, cinnamic acid, methane- or ethane-sulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 1,5-naphthalene-disulfonic acid, 2-, 3- or 4-methylbenzenesulfonic acid, methylsulfuric acid, ethylsulfuric acid, dodecyl sulfate, N-cyclohexylaminosulfonic acid, N-methyl-, N-ethyl- or N-propyl-aminosulfonic acid, or other organic protic acids, such as ascorbic acid.

[0171] b) Vinetok

[0172] On one hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API, a surfactant, a hydrophilic polymer, optionally an inorganic or organic acid, and optionally an adsorbent. On the other hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API. In some embodiments, the API is a free base of venetoclax (i.e., venetoclax) or a pharmaceutically acceptable salt thereof. In some embodiments, the API is a pharmaceutically acceptable salt of venetoclax.

[0173] In some embodiments, ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 3% by weight to about 60% by weight of ASD. In some embodiments, ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 45% by weight of ASD. In some embodiments, ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 40% by weight of ASD. In some embodiments, ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 15% by weight to about 35% by weight of ASD. In some embodiments, ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is about 31% by weight of ASD.

[0174] In some embodiments, venetoclax free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 5% to about 60%. In some embodiments, venetoclax free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 10% to about 50%. In some embodiments, venetoclax free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 15% to about 30%. In some embodiments, venetoclax free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 25% to about 40%. In some embodiments, venetoc free base or a pharmaceutically acceptable salt thereof is present in amounts of about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 5% to about 35%, about 5% to about 40%, about 5% to about 45%, about 5% to about 50%, about 5% to about 55%, about 5% to about 60%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%. %, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% The amorphous solids are present in the dispersion at a weight percentage of about 60%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 50% to about 55%, about 50% to about 60%, or about 55% to about 60%.In some embodiments, venetoclax free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, venetoclax free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or about 55%. In some embodiments, the free base of venetoc or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion in weight percentages of up to about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%.

[0175] In some embodiments, ASD comprises a surfactant. In some embodiments, the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or a combination thereof. In some embodiments, the surfactant comprises lecithin and TPGS. In some embodiments, the surfactant comprises lecithin. In some embodiments, the surfactant comprises PEG. In some embodiments, the surfactant comprises a block copolymer of polyethylene glycol and polypropylene glycol. In some embodiments, the surfactant comprises SLS. In some embodiments, the surfactant comprises a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam. In some embodiments, the surfactant comprises polyoxyethylene hydrogenated castor oil (e.g., sold under the trade name RH40). In some embodiments, the surfactant comprises polysorbate. In some embodiments, the surfactant comprises polyoxyethylene glycerol (e.g., Labrasol or Gelucire). In some embodiments, the surfactant comprises TPGS. In some embodiments, the surfactant is present in an amount of about 5% by weight to about 60% by weight of ASD.

[0176] In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is nonionic. In some embodiments, the hydrophilic polymer is ionic. In some embodiments, the hydrophilic polymer is an enteric polymer. In some embodiments, the hydrophilic polymer is copovidone. In some embodiments, the hydrophilic polymer is HPMCAS. In some embodiments, the hydrophilic polymer is a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam (PVAc-PVCap-PEG). In some embodiments, the hydrophilic polymer is polymethacrylate (e.g., Eudragit). In some embodiments, the pharmaceutical composition described herein comprises ASD, wherein the ASD comprises a hydrophilic polymer, wherein the hydrophilic polymer is VA64. In some embodiments, the hydrophilic polymer is present in an amount of about 1% by weight to about 80% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 10% by weight to about 60% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% by weight to about 50% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% by weight to about 40% by weight of the ASD.

[0177] In some embodiments, ASD comprises an inorganic acid or an organic acid. In some embodiments, ASD comprises an organic acid. In some embodiments, the organic acid is citric acid. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 40% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 30% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 3% by weight to about 20% by weight of ASD.

[0178] In some embodiments, the ASD optionally includes an adsorbent. In some embodiments, the amount of adsorbent is from about 1% to 20% by weight of the ASD. In some embodiments, the amount of adsorbent is from about 1% to 40% by weight of the ASD. In some embodiments, the amount of adsorbent is from about 10% to 40% by weight of the ASD. In some embodiments, the adsorbent is silica.

[0179] In some embodiments, the ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 40% by weight of the ASD. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the surfactant comprises lecithin, TPGS, or a combination thereof. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the hydrophilic polymer is copovidone, HPMCAS, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 1% by weight to 20% by weight of the ASD. In some embodiments, the organic acid is citric acid. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the adsorbent is silica.

[0180] In some embodiments, an ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 20% to about 40% by weight of the ASD. In some embodiments, the ASD comprises a surfactant, said surfactant being from about 20% to about 40% by weight of the ASD. In some embodiments, the surfactant comprises lecithin, TPGS, or a combination thereof. In some embodiments, the ASD comprises a hydrophilic polymer, said hydrophilic polymer being from about 20% to about 40% by weight of the ASD. In some embodiments, the hydrophilic polymer is copovidone, HPMCAS, or a combination thereof. In some embodiments, the ASD comprises an organic acid, said organic acid being from about 3% to 15% by weight of the ASD. In some embodiments, the organic acid is citric acid.

[0181] In some embodiments, the pharmaceutical compositions described herein comprise ASD, which comprises venetoclax free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is about 31% by weight of the ASD. In some embodiments, the ASD comprises a surfactant, which is about 31% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer, which is about 31% by weight of the ASD. In some embodiments, the hydrophilic polymer is copovidone. In some embodiments, the ASD comprises an organic acid, which is about 7% by weight of the ASD. In some embodiments, the organic acid is citric acid.

[0182] In some embodiments, the pharmaceutical compositions described herein comprise ASD, the ASD comprising an amount of venetoclax or a pharmaceutically acceptable salt thereof, the amount of venetoclax or a pharmaceutically acceptable salt thereof being from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the amount of venetoclax or a pharmaceutically acceptable salt thereof is from about 20% by weight to about 50% by weight of the ASD. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the amount of the surfactant is from about 20% by weight to about 40% by weight of the ASD. In some embodiments, the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters (e.g., Labrasol or Gelucire), polysorbate, or combinations thereof. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 20% by weight to about 40% by weight of the ASD. In some embodiments, the hydrophilic polymer is copovidone, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam (PVAc-PVCap-PEG), polymethacrylate, HPMCAS, or a combination thereof. In some embodiments, the ASD contains an organic acid. In some embodiments, the amount of the organic acid is from about 1% to 20% by weight of the ASD. In some embodiments, the amount of the organic acid is from about 3% to 20% by weight of the ASD. In some embodiments, the organic acid is citric acid. In some embodiments, the ASD contains an adsorbent. In some embodiments, the amount of the adsorbent is from about 5% to 40% by weight of the ASD. In some embodiments, the amount of the adsorbent is from about 10% to 40% by weight of the ASD. In some embodiments, the adsorbent is silica.

[0183] In some embodiments, the pharmaceutical composition described herein comprises ASD, which comprises venetoclax free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is about 10-30% by weight of the ASD. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is about 10-30% by weight of the ASD. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is about 15-25% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is about 10% to 60% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 18% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 20% by weight of the ASD. In some embodiments, the hydrophilic polymer is L100. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is about 10% to about 40% by weight of the ASD. In some embodiments, the amount of the surfactant is about 18% by weight of the ASD. In some embodiments, the surfactant is present in an amount of about 20% by weight of the ASD. In some embodiments, the surfactant is TPGS. In some embodiments, TPGS is present in an amount of about 18-20% by weight of the ASD. In some embodiments, the ASD contains an organic acid. In some embodiments, the organic acid is citric acid. In some embodiments, citric acid is present in an amount of about 10% to 20% by weight of the ASD. In some embodiments, the ASD contains an adsorbent. In some embodiments, the adsorbent is present in an amount of about 25% to about 40% by weight of the ASD. In some embodiments, the adsorbent is SiO2. In some embodiments, SiO2 is present in an amount of about 27-35% by weight of the ASD.

[0184] In some embodiments, the pharmaceutical composition described herein comprises ASD, the ASD comprising: venetoclax free base or a pharmaceutically acceptable salt thereof, the amount of the venetoclax free base or a pharmaceutically acceptable salt thereof being about 24% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being about 24% by weight of the ASD, and wherein the hydrophilic polymer is L100; a surfactant, the amount of the surfactant being about 18% by weight of the ASD, wherein the surfactant is TPGS; and an absorbent, the amount of the absorbent being about 36% by weight of the ASD, wherein the absorbent is SiO2.

[0185] In some embodiments, the pharmaceutical composition described herein comprises ASD, the ASD consisting of: venetoclax free base or a pharmaceutically acceptable salt thereof, the amount of the venetoclax free base or a pharmaceutically acceptable salt thereof being from about 18% to about 20% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being from about 18% to about 20% by weight of the ASD, wherein the hydrophilic polymer is VA64; a surfactant, the amount of the surfactant being from about 10% to 18% by weight of the ASD, wherein the surfactant is TPGS; an organic acid, the organic acid being present in an amount of about 18-20% by weight of the ASD, wherein the organic acid is citric acid; and an adsorbent, the amount of the adsorbent being from about 27% to 30% by weight of the ASD, wherein the adsorbent is SiO2.

[0186] In some embodiments, the pharmaceutical compositions comprising ASD described herein are formulated in a unit dosage form comprising venetoclax or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax or a pharmaceutically acceptable salt thereof is from about 60 mg to about 300 mg. In some embodiments, the amount of venetoclax or a pharmaceutically acceptable salt thereof is from about 80 mg to about 120 mg. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 20 mg to about 450 mg. In some embodiments, the amount of the surfactant is from about 70 mg to about 130 mg. In some embodiments, the surfactant is TPGS, lecithin, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol ester, polysorbate, or a combination thereof. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 50 mg to about 450 mg. In some embodiments, the amount of the hydrophilic polymer is from about 70 mg to about 130 mg. In some embodiments, the hydrophilic polymer is copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam (PVAc-PVCap-PEG), HPMCAS, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 5 mg to about 150 mg. In some embodiments, the amount of the organic acid is from about 10 mg to about 40 mg. In some embodiments, the organic acid is citric acid. In some embodiments, ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 10 mg to about 300 mg. In some embodiments, the amount of the adsorbent is from about 50 mg to about 180 mg. In some embodiments, the adsorbent is silica.

[0187] In some embodiments, ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 60 mg to about 140 mg. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 50 mg to about 150 mg. In some embodiments, the surfactant is TPGS. In some embodiments, ASD comprises a hydrophilic polymer, the amount of which is from about 50 mg to about 150 mg. In some embodiments, the hydrophilic polymer is copovidone, HPMCAS, or a combination of both. In some embodiments, ASD comprises an organic acid, the amount of which is from about 5 mg to about 50 mg. In some embodiments, the organic acid is citric acid.

[0188] In some embodiments, ASD comprises venetoclax free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of venetoclax free base or a pharmaceutically acceptable salt thereof is from about 80 mg to about 120 mg. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 70 mg to about 130 mg. In some embodiments, the surfactant is TPGS. In some embodiments, ASD comprises a hydrophilic polymer, the amount of which is from about 70 mg to about 130 mg. In some embodiments, the hydrophilic polymer is copovidone, HPMCAS, or a combination of both. In some embodiments, ASD comprises an organic acid, the amount of which is from about 10 mg to about 40 mg. In some embodiments, the organic acid is citric acid.

[0189] In some embodiments, the pharmaceutical composition containing an ASD has acceptable storage stability, wherein the ASD comprises a free venetoclax base or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition is chemically stable at 75°C / 75% RH for at least 2 weeks, wherein the degradation of the API in the storage-stable pharmaceutical composition is less than 5% at the end of the storage period. In some embodiments, the pharmaceutical composition is stable at 40°C / 75% RH for at least 6 months, wherein the storage-stable pharmaceutical composition has less than 0.5% of any impurities at the end of the storage period. In some embodiments, the pharmaceutical composition is stable at 25°C / 60% RH for at least 2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months, or 24 months, wherein the storage-stable pharmaceutical composition has less than 0.5% of any impurities at the end of the storage period.

[0190] In some embodiments, when administered orally, the AUC, AUC inf or AUC lastWhen measured, the bioavailability of the pharmaceutical compositions described herein is superior to that of a corresponding reference composition comprising a pharmaceutically acceptable salt crystallized therein. In some embodiments, the bioavailability is measured after oral administration in AUC, AUCinf, or AUC. last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions comprising pharmaceutically acceptable salts crystallized therein. In some embodiments, when administered orally, C max When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions comprising pharmaceutically acceptable salts crystallized therein. In some embodiments, when administered orally, the bioavailability is measured in AUC, AUCinf, or AUC. last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of VENCLEXTA capsules containing their pharmaceutically acceptable salts. In some embodiments, when administered orally, C maxWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of VENCLEXTA. In some embodiments, the bioavailability exhibited by the pharmaceutical compositions is about 1.1 to about 10 times higher than that of VENCLEXTA. In some embodiments, the bioavailability of the pharmaceutical composition is about 1.1 times to about 2 times, about 1.1 times to about 3 times, about 1.1 times to about 4 times, about 1.1 times to about 5 times, about 1.1 times to about 6 times, about 1.1 times to about 7 times, about 1.1 times to about 8 times, about 1.1 times to about 10 times, about 1.5 times to about 2 times, about 1.5 times to about 3 times, about 1.5 times to about 4 times, about 1.5 times to about 5 times, about 1.5 times to about 6 times, about 1.5 times to about 7 times, about 1.5 times to about 8 times, about 1.5 times to about 10 times, about 2 times to about 4 times, about 2 times Up to 5 times, about 2 times to 6 times, about 2 times to 7 times, about 2 times to 8 times, about 2 times to 10 times, about 3 times to 4 times, about 3 times to 5 times, about 3 times to 6 times, about 3 times to 7 times, about 3 times to 8 times, about 3 times to 10 times, about 4 times to 5 times, about 4 times to 6 times, about 4 times to 7 times, about 4 times to 8 times, about 4 times to 10 times, about 5 times to 6 times, about 5 times to 7 times, about 5 times to 8 times, about 5 times to 10 times, about 6 times to 7 times, about 6 times to 8 times, about 6 times to 10 times, about 7 times to 8 times, about 7 times to 10 times, or about 8 times to 10 times. In some embodiments, the pharmaceutical composition comprises ASD, said ASD comprising venetoclax or a pharmaceutically acceptable salt thereof. In some embodiments, bioavailability is measured under feeding conditions. In some embodiments, bioavailability is measured under fasting conditions.

[0191] In some embodiments, after oral administration under fasting conditions, C max or AUC last When measured, the bioavailability of the pharmaceutical composition is about 75% to about 200% of the bioavailability of a corresponding reference composition containing venetoclax, wherein the reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, after oral administration under fasting conditions, C max or AUC lastWhen measured, the bioavailability of the pharmaceutical composition is about 125% to about 200% of the bioavailability of a corresponding reference composition containing venetoclax, wherein the reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, after oral administration under fasting conditions, C max or AUC last When measured, the bioavailability of the pharmaceutical composition is about 150% to about 200% of the bioavailability of a corresponding reference composition containing venetoclax, wherein the reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, when administered orally, the bioavailability is measured in AUC, AUCinf, or AUC. last Or C max When measured, the pharmaceutical compositions described herein exhibit bioavailability that is at least about 1.1 times, about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, or about 8 times higher than the bioavailability of VENCLEXTA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 2 times higher than the bioavailability of VENCLEXTA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 4 times higher than the bioavailability of VENCLEXTA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at most about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, or about 10 times higher than the bioavailability of VENCLEXTA. In some embodiments, bioavailability is measured in a canine model under fasting conditions. In some embodiments, bioavailability is measured in a canine model under feeding conditions. In some embodiments, AUC, AUCinf, or AUC is measured after oral administration. last When the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, when administered orally with C maxDuring measurement, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 40%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 20%. In some embodiments, bioavailability is measured in a canine model. In some embodiments, the canine model is a beagle. In some embodiments, the pharmaceutical composition comprises an ASD comprising venetoc or a pharmaceutically acceptable salt thereof. In some embodiments, bioavailability is measured under fed conditions. In some embodiments, bioavailability is measured under fasted conditions.

[0192] In some embodiments, salts of venetoc compounds are formed, for example, by venetoc with a compound containing a basic nitrogen atom as an acid addition salt (e.g., having an organic or inorganic acid), such as a pharmaceutically acceptable salt. Suitable inorganic acids are, for example, hydrohalic acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, for example, carboxylic acids, phosphonic acids, sulfonic acids or aminosulfonic acids, acetic acid, propionic acid, octanoic acid, decanoic acid, dodecanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, octanoic acid, azelaic acid, malic acid, tartaric acid, citric acid, amino acids such as glutamic acid or aspartic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, cyclohexanecarboxylic acid, adamantanecarboxylic acid, benzoic acid, salicylic acid, 4-aminosalicylic acid, phthalic acid, etc. Dicarboxylic acid, phenylacetic acid, mandelic acid, cinnamic acid, methane- or ethane-sulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 1,5-naphthalene-disulfonic acid, 2-, 3- or 4-methylbenzenesulfonic acid, methylsulfuric acid, ethylsulfuric acid, dodecyl sulfate, N-cyclohexylaminosulfonic acid, N-methyl-, N-ethyl- or N-propyl-aminosulfonic acid, or other organic protic acids, such as ascorbic acid.

[0193] c) Abiraterone acetate

[0194] On one hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API, a hydrophilic polymer, optionally a surfactant, optionally an inorganic or organic acid, and optionally an adsorbent. On the other hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API. In some embodiments, the API is abiraterone free base or a pharmaceutically acceptable salt thereof. In some embodiments, the API is abiraterone acetate.

[0195] In some embodiments, ASD comprises abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate), wherein the amount of the abiraterone free base or a pharmaceutically acceptable salt thereof is from about 3% to about 60% by weight of ASD. In some embodiments, the abiraterone free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 10% to about 50%. In some embodiments, the abiraterone free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 15% to about 30%. In some embodiments, the abiraterone free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 25% to about 40%. In some embodiments, ASD comprises abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate), wherein the amount of the abiraterone free base or a pharmaceutically acceptable salt thereof is from about 3% to about 30% by weight of ASD. In some embodiments, ASD comprises abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate), wherein the amount of the abiraterone free base or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 25% by weight of ASD. In some embodiments, ASD comprises abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate), wherein the amount of the abiraterone free base or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 20% by weight of ASD. In some embodiments, ASD comprises abiraterone free base or abiraterone acetate, wherein the amount of the abiraterone free base or abiraterone acetate thereof is about 10% by weight of ASD. In some embodiments, ASD comprises abiraterone free base or abiraterone acetate, wherein the amount of the abiraterone free base or abiraterone acetate is about 20% by weight of ASD.

[0196] In some embodiments, abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate) is present in the amorphous solid dispersion at a weight percentage of about 5% to about 60%.In some embodiments, abiraterone free base or abiraterone acetate is present in amounts of about 5% to about 10% by weight, about 5% to about 15% by weight, about 5% to about 20% by weight, about 5% to about 25% by weight, about 5% to about 30% by weight, about 5% to about 35% by weight, about 5% to about 40% by weight, about 5% to about 45% by weight, about 5% to about 50% by weight, about 5% to about 55% by weight, about 5% to about 60% by weight, about 10% to about 15% by weight, about 10% to about 20% by weight, about 10% to about 25% by weight, about 10% to about 30% by weight, about 10% to about 35% by weight, about 10 wt% to about 40 wt%, about 10 wt% to about 45 wt%, about 10 wt% to about 50 wt%, about 10 wt% to about 55 wt%, about 10 wt% to about 60 wt%, about 15 wt% to about 20 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 30 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 40 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 50 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 60 wt%, about 20 wt% to about 25 wt%, about 20 wt% to about 30 wt%, about 20 wt% to about 35 wt%, about 20 wt% to about 40 wt%, about 20 wt% to about 45 wt%, about 20 wt% to about 50 wt%, about 20 wt% to about 55 wt%, about 20 wt% to about 60 wt%, about 25 wt% to about 30 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 40 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 50 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 60 wt%, about 30 wt% to about 35 wt%, about 30 wt% to about 40 wt%, about 30 wt% to about 45 wt%, about 30 wt% to about 50 wt%, about 30 wt% to about 55 wt%, An amount of about 30 wt% to about 60 wt%, about 35 wt% to about 40 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 50 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 60 wt%, about 40 wt% to about 45 wt%, about 40 wt% to about 50 wt%, about 40 wt% to about 55 wt%, about 40 wt% to about 60 wt%, about 45 wt% to about 50 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 60 wt%, about 50 wt% to about 55 wt%, about 50 wt% to about 60 wt%, or about 55 wt% to about 60 wt% is present in the amorphous solid dispersion.In some embodiments, abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate) is present in the amorphous solids dispersion at a weight percentage of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, abiraterone free base or abiraterone acetate is present in the amorphous solids dispersion at a weight percentage of at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or about 55%. In some embodiments, abiraterone free base or abiraterone acetate is present in the amorphous solid dispersion in weight percentages of up to about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%.

[0197] In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is nonionic. In some embodiments, the hydrophilic polymer is ionic. In some embodiments, the hydrophilic polymer is an enteric polymer. In some embodiments, the pharmaceutical composition described herein comprises ASD, which comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is HPMCAS. In some embodiments, the hydrophilic polymer is polymethacrylate. In some embodiments, the hydrophilic polymer is copovidone. In some embodiments, the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone or a combination thereof. In some embodiments, the hydrophilic polymer comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters (e.g., Labrasol or Gelucire), polysorbate, or a combination thereof. In some embodiments, the hydrophilic polymer is present in an amount from about 1% by weight to about 80% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 5% to about 70% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 10% to about 60% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% to about 50% by weight of the ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% to about 40% by weight of the ASD.

[0198] In some embodiments, the ASD optionally comprises a surfactant. In some embodiments, the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or a combination thereof. In some embodiments, the surfactant comprises lecithin and TPGS. In some embodiments, the surfactant comprises lecithin. In some embodiments, the surfactant comprises PEG. In some embodiments, the surfactant comprises a block copolymer of polyethylene glycol and polypropylene glycol. In some embodiments, the surfactant comprises SLS. In some embodiments, the surfactant comprises a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam. In some embodiments, the surfactant comprises polyoxyethylene hydrogenated castor oil (e.g., sold under the trade name RH40). In some embodiments, the surfactant comprises polysorbate. In some embodiments, the surfactant comprises polyoxyethylene glycerol (e.g., Labrasol or Gelucire). In some embodiments, the surfactant comprises TPGS. In some embodiments, the surfactant is present in an amount of about 5% by weight to about 50% by weight of the ASD. In some embodiments, the surfactant is present in an amount of about 5% to about 40% by weight of ASD. In some embodiments, the surfactant is present in an amount of about 5% to about 30% by weight of ASD.

[0199] In some embodiments, the ASD optionally includes an adsorbent. In some embodiments, the adsorbent is silica. In some embodiments, the adsorbent is present in an amount of about 1% to about 50% by weight of the ASD. In some embodiments, the adsorbent is present in an amount of about 1% to about 40% by weight of the ASD.

[0200] In some embodiments, ASD optionally contains an inorganic acid or an organic acid. In some embodiments, ASD optionally contains an organic acid. In some embodiments, ASD contains an organic acid. In some embodiments, the organic acid is malic acid. In some embodiments, the organic acid is a fatty acid such as oleic acid. In some embodiments, the organic acid is tartaric acid. In some embodiments, the organic acid is malic acid, tartaric acid, oleic acid, or a combination thereof. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 40% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 30% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 20% by weight of ASD.

[0201] In some embodiments, the ASD comprises an adsorbent. In some embodiments, the adsorbent is SiO2. In some embodiments, the adsorbent is magnesium aluminum silicate. In some embodiments, the adsorbent is silicon dioxide or magnesium aluminum silicate or a combination thereof. In some embodiments, the adsorbent is present in an amount of about 10% by weight to about 40% by weight of the ASD. In some embodiments, the adsorbent is present in an amount of about 1% by weight to about 30% by weight of the ASD. In some embodiments, the adsorbent is present in an amount of about 1% by weight to about 20% by weight of the ASD.

[0202] In some embodiments, ASD comprises abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate). In some embodiments, the amount of abiraterone free base or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 40% by weight of ASD. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 30% by weight to about 95% by weight of ASD. In some embodiments, the amount of the hydrophilic polymer is from about 30% by weight to about 90% by weight of ASD. In some embodiments, the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 10% by weight to about 40% by weight of ASD. In some embodiments, the surfactant is lecithin or TPGS, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 5% by weight to 30% by weight of ASD. In some embodiments, the organic acid is tartaric acid, oleic acid, or a combination thereof. In some embodiments, ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 1% by weight to 40% by weight of ASD. In some embodiments, the adsorbent is silicon dioxide or magnesium aluminum silicate or a combination thereof.

[0203] In some embodiments, the ASD comprises abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate). In some embodiments, the amount of abiraterone free base or a pharmaceutically acceptable salt thereof is from about 8% by weight to about 30% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 50% by weight to about 91% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 30% by weight to about 90% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone, or a combination thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 15% by weight to about 30% by weight of the ASD. In some embodiments, the surfactant is lecithin or TPGS, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 5% by weight to 30% by weight of the ASD. In some embodiments, the organic acid is tartaric acid, oleic acid, or a combination thereof. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 1% by weight to 40% by weight of the ASD. In some embodiments, the adsorbent is silicon dioxide or magnesium aluminum silicate or a combination thereof.

[0204] In some embodiments, the pharmaceutical compositions described herein comprise ASD, the ASD comprising abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate), the amount of the abiraterone free base or a pharmaceutically acceptable salt thereof being about 10% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer, the amount of the hydrophilic polymer being about 90% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is about 5% by weight to 30% by weight of the ASD. In some embodiments, the organic acid is tartaric acid, oleic acid, or a combination thereof. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is about 1% by weight to 40% by weight of the ASD. In some embodiments, the adsorbent is silica or magnesium aluminum silicate, or a combination thereof.

[0205] In some embodiments, the pharmaceutical composition described herein comprises ASD, which comprises abiraterone acetate or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of abiraterone acetate or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 50% by weight of the ASD. In some embodiments, the amount of abiraterone acetate or a pharmaceutically acceptable salt thereof is from about 10-30% by weight of the ASD. In some embodiments, the amount of abiraterone acetate or a pharmaceutically acceptable salt thereof is from about 15-20% by weight of the ASD. In some embodiments, the amount of abiraterone acetate or a pharmaceutically acceptable salt thereof is from about 16% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 5% by weight to about 95% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 95% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 95% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 30% by weight to about 80% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 50% to about 80% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 10% to about 60% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 38% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the hydrophilic polymer is polyvinyl acetate. In some embodiments, the hydrophilic polymer is a graft copolymer based on polyvinylcaprolactam. In some embodiments, the hydrophilic polymer is PVP. In some embodiments, the hydrophilic polymer is copovidone. In some embodiments, the hydrophilic polymer is HPMC, HPMC, polyvinyl acetate, a graft copolymer based on polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the hydrophilic polymer is HPMC-LF. In some embodiments, the ASD contains a surfactant. In some embodiments, the amount of the surfactant is from about 10% to about 40% by weight of the ASD. In some embodiments, the amount of the surfactant is from about 10% to about 30% by weight of the ASD. In some embodiments, the amount of surfactant is about 20% by weight of ASD. In some embodiments, the surfactant comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters, polysorbate esters, or combinations thereof. In some embodiments, the surfactant is TPGS or lecithin or combinations thereof.In some embodiments, TPGS is present in an amount of about 10% by weight of ASD. In some embodiments, lecithin is present in an amount of about 15% by weight to about 20% by weight of ASD. In some embodiments, ASD comprises an organic acid. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 35% by weight of ASD. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 30% by weight of ASD. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 20% by weight of ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, tartaric acid is present in an amount of about 19% by weight of ASD. In some embodiments, the organic acid is oleic acid. In some embodiments, oleic acid is present in an amount of about 13% by weight of ASD. In some embodiments, ASD comprises an adsorbent. In some embodiments, the adsorbent is present in an amount of about 15% by weight to about 40% by weight of ASD. In some embodiments, the adsorbent is present in an amount of about 20% by weight to about 40% by weight of ASD. In some embodiments, the adsorbent is SiO2. In some embodiments, SiO2 is present in an amount of about 27% by weight of ASD. In some embodiments, the adsorbent is magnesium aluminum silicate. In some embodiments, magnesium aluminum silicate is present in an amount of about 38% by weight of ASD.

[0206] In some embodiments, the pharmaceutical composition described herein comprises ASD, the ASD comprising: abiraterone acetate or a pharmaceutically acceptable salt thereof, the amount of the abiraterone acetate or a pharmaceutically acceptable salt thereof being about 9% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being about 91% by weight of the ASD, and wherein the hydrophilic polymer is HPMCAS.

[0207] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: abiraterone acetate or a pharmaceutically acceptable salt thereof, in an amount of about 10% to about 30% by weight of the ASD; a hydrophilic polymer, in an amount of about 30% to about 60% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS; and a surfactant, in an amount of about 10% to about 30% by weight of the ASD, wherein the surfactant is lecithin.

[0208] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: abiraterone acetate or a pharmaceutically acceptable salt thereof, in an amount of about 13% by weight of the ASD; a hydrophilic polymer, in an amount of about 38% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS; oleic acid, in an amount of about 13% by weight of the ASD; and an adsorbent, in an amount of about 38% by weight of the ASD, wherein the adsorbent is magnesium aluminum silicate.

[0209] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: abiraterone acetate or a pharmaceutically acceptable salt thereof, in an amount of about 18% by weight of the ASD; a hydrophilic polymer, in an amount of about 18% by weight of the ASD, wherein the hydrophilic polymer is VA64; a surfactant, in an amount of about 9% by weight of the ASD, wherein the surfactant is lecithin, TPGS, or a combination thereof; tartaric acid, in an amount of about 18% by weight of the ASD; and an adsorbent, in an amount of about 27% by weight of the ASD, wherein the adsorbent is SiO2.

[0210] In some embodiments, the pharmaceutical compositions described herein comprise ASD, the ASD comprising abiraterone free base or a pharmaceutically acceptable salt thereof (such as abiraterone acetate), the amount of the abiraterone free base or a pharmaceutically acceptable salt thereof being about 20% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer, the amount of the hydrophilic polymer being about 60% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone, or a combination thereof. In some embodiments, the ASD comprises a surfactant, the amount of the surfactant being about 20% by weight of the ASD. In some embodiments, the surfactant is lecithin or TPGS, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the organic acid is about 5% by weight to 30% by weight of the ASD. In some embodiments, the organic acid is tartaric acid, oleic acid, or a combination thereof. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the adsorbent is about 1% by weight to 40% by weight of the ASD. In some embodiments, the adsorbent is silica or magnesium aluminum silicate, or a combination thereof. In some embodiments, the pharmaceutical compositions comprising ASD described herein are formulated in unit dosage forms.

[0211] In some embodiments, ASD comprises abiraterone free base or abiraterone acetate in an amount of about 20 mg to about 200 mg. In some embodiments, ASD comprises a hydrophilic polymer in an amount of about 80 mg to about 700 mg. In some embodiments, the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone, or a combination thereof. In some embodiments, ASD comprises a surfactant in an amount of about 10 mg to about 80 mg. In some embodiments, the surfactant is lecithin or TPGS, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the organic acid is in an amount of about 10 mg to about 250 mg. In some embodiments, the organic acid is tartaric acid, oleic acid, or a combination thereof. In some embodiments, ASD comprises an adsorbent. In some embodiments, the adsorbent is in an amount of about 10 mg to about 400 mg. In some embodiments, the adsorbent is silica or magnesium aluminum silicate, or a combination thereof. In some embodiments, the pharmaceutical compositions comprising ASD described herein are formulated in unit dosage forms.

[0212] In some embodiments, ASD comprises abiraterone free base or abiraterone acetate in an amount of about 30 mg to about 150 mg. In some embodiments, ASD comprises a hydrophilic polymer in an amount of about 100 mg to about 600 mg. In some embodiments, the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone, or a combination thereof. In some embodiments, ASD comprises a surfactant in an amount of about 20 mg to about 60 mg. In some embodiments, the surfactant is lecithin or TPGS, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the organic acid is in an amount of about 10 mg to about 150 mg. In some embodiments, the organic acid is tartaric acid, oleic acid, or a combination thereof. In some embodiments, ASD comprises an adsorbent. In some embodiments, the adsorbent is in an amount of about 20 mg to about 180 mg. In some embodiments, the adsorbent is silica or magnesium aluminum silicate, or a combination thereof. In some embodiments, the pharmaceutical compositions comprising ASD described herein are formulated in unit dosage forms.

[0213] In some embodiments, when administered orally, the AUC, AUC inf or AUC last When measured, the bioavailability of the pharmaceutical composition described herein is superior to that of a corresponding reference composition containing abiraterone acetate. In some embodiments, when measured after oral administration, the bioavailability is measured in AUC, AUCinf, or AUC. lastWhen measured, the bioavailability of the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing abiraterone acetate. In some embodiments, when administered orally, C max When measured, the bioavailability of the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing abiraterone acetate. In some embodiments, when administered orally, the bioavailability is measured in AUC, AUCinf, or AUC. last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of ZYTIGA tablets containing abiraterone acetate. In some embodiments, when administered orally, C maxWhen measured, the bioavailability of the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of ZYTIGA capsules containing abiraterone acetate. In some embodiments, the bioavailability of the pharmaceutical compositions is about 1.1 to about 10 times higher than that of ZYTIGA. In some embodiments, the bioavailability of the pharmaceutical composition is about 1.1 times to about 2 times, about 1.1 times to about 3 times, about 1.1 times to about 4 times, about 1.1 times to about 5 times, about 1.1 times to about 6 times, about 1.1 times to about 7 times, about 1.1 times to about 8 times, about 1.1 times to about 10 times, about 1.5 times to about 2 times, about 1.5 times to about 3 times, about 1.5 times to about 4 times, about 1.5 times to about 5 times, about 1.5 times to about 6 times, about 1.5 times to about 7 times, about 1.5 times to about 8 times, about 1.5 times to about 10 times, about 2 times to about 4 times, about 2 times to Approximately 5 times, approximately 2 times to approximately 6 times, approximately 2 times to approximately 7 times, approximately 2 times to approximately 8 times, approximately 2 times to approximately 10 times, approximately 3 times to approximately 4 times, approximately 3 times to approximately 5 times, approximately 3 times to approximately 6 times, approximately 3 times to approximately 7 times, approximately 3 times to approximately 8 times, approximately 3 times to approximately 10 times, approximately 4 times to approximately 5 times, approximately 4 times to approximately 6 times, approximately 4 times to approximately 7 times, approximately 4 times to approximately 8 times, approximately 4 times to approximately 10 times, approximately 5 times to approximately 6 times, approximately 5 times to approximately 7 times, approximately 5 times to approximately 8 times, approximately 5 times to approximately 10 times, approximately 6 times to approximately 7 times, approximately 6 times to approximately 8 times, approximately 6 times to approximately 10 times, approximately 7 times to approximately 8 times, approximately 7 times to approximately 10 times, or approximately 8 times to approximately 10 times. In some embodiments, the pharmaceutical composition comprises ASD, said ASD comprising abiraterone or abiraterone acetate. In some embodiments, bioavailability is measured under fasting conditions.

[0214] In some embodiments, when administered orally, the AUC, AUCinf, or AUC is used as the indicative value. last Or C maxWhen measured, the bioavailability of the pharmaceutical composition described herein is at least about 1.1 times, about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, or about 8 times higher than that of ZYTIGA. In some embodiments, the bioavailability of the pharmaceutical composition is at least about 2 times higher than that of ZYTIGA. In some embodiments, the bioavailability of the pharmaceutical composition is at least about 4 times higher than that of ZYTIGA. In some embodiments, the bioavailability of the pharmaceutical composition is at most about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, or about 10 times higher than that of ZYTIGA. In some embodiments, bioavailability is measured in a canine model under fasting conditions. In some embodiments, bioavailability is measured in a canine model under feeding conditions. In some embodiments, AUC, AUCinf, or AUC is measured after oral administration. last When the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, when administered orally with C max During measurement, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 40%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 20%. In some embodiments, bioavailability is measured in a canine model. In some embodiments, the canine model is a beagle. In some embodiments, bioavailability is measured under fasting conditions. In some embodiments, the pharmaceutical composition comprises an ASD, wherein the ASD comprises abiraterone or abiraterone acetate.

[0215] In some embodiments, when administered orally at AUC last Or C maxWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is about 30% to about 1500%, 40% to about 1000%, 50% to about 500%, about 70% to about 300%, 75% to about 200%, or about 100% to about 200% of the bioavailability of a corresponding reference composition containing abiraterone acetate, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, the dose of the reference composition is at least about 1.1 times the dose of the pharmaceutical composition. In some embodiments, the dose of the reference composition is at least about 1.1 times, about 1.5 times, about 2 times, about 2.5 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, or about 10 times the dose of the pharmaceutical composition. In some embodiments, the pharmaceutical composition contains an ASD, which contains abiraterone free base or abiraterone acetate. In some embodiments, the reference composition contains abiraterone free base or abiraterone acetate, wherein the reference composition does not contain an ASD. In some embodiments, the reference composition is ZYTIGA. In some embodiments, bioavailability is measured under fasting conditions.

[0216] In some embodiments, when administered orally at AUC last When measured, the bioavailability of the pharmaceutical compositions described herein is about 75% to about 200% of the bioavailability of a corresponding reference composition containing abiraterone acetate, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is at least 3 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is ZYTIGA. In some embodiments, bioavailability is measured under fasting conditions.

[0217] In some embodiments, when administered orally with C max When measured, the bioavailability of the pharmaceutical compositions described herein is about 100% to about 200% of the bioavailability of a corresponding reference composition containing abiraterone acetate, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is at least 3 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is ZYTIGA. In some embodiments, bioavailability is measured under fasting conditions.

[0218] In some embodiments, when administered orally at AUC lastWhen measured, the bioavailability of the pharmaceutical compositions described herein is about 90% to about 110% of the bioavailability of a corresponding reference composition containing abiraterone acetate, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about 5 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is ZYTIGA. In some embodiments, bioavailability is measured under fasting conditions.

[0219] In some embodiments, when administered orally with C max When measured, the bioavailability of the pharmaceutical compositions described herein is about 100% to about 175% of the bioavailability of a corresponding reference composition containing abiraterone acetate, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about 5 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is ZYTIGA. In some embodiments, bioavailability is measured under fasting conditions.

[0220] In some embodiments, the salt of the abiraterone compound is formed, for example, by abiraterone with a basic nitrogen atom as an acid addition salt (e.g., having an organic or inorganic acid), such as a pharmaceutically acceptable salt. Suitable inorganic acids are, for example, hydrohalic acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, for example, carboxylic acids, phosphonic acids, sulfonic acids or aminosulfonic acids, acetic acid, propionic acid, octanoic acid, decanoic acid, dodecanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, octanoic acid, azelaic acid, malic acid, tartaric acid, citric acid, amino acids such as glutamic acid or aspartic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, cyclohexanecarboxylic acid, adamantanecarboxylic acid, benzoic acid, salicylic acid, 4-aminosalicylic acid, phthalic acid, etc. Dicarboxylic acid, phenylacetic acid, mandelic acid, cinnamic acid, methane- or ethane-sulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 1,5-naphthalene-disulfonic acid, 2-, 3- or 4-methylbenzenesulfonic acid, methylsulfuric acid, ethylsulfuric acid, dodecyl sulfate, N-cyclohexylaminosulfonic acid, N-methyl-, N-ethyl- or N-propyl-aminosulfonic acid, or other organic protic acids, such as ascorbic acid.

[0221] d) Alectinib hydrochloride

[0222] On one hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API, a hydrophilic polymer, a surfactant, optionally an organic acid, and optionally an adsorbent. On the other hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API. In some embodiments, the API is alectinib free base or a pharmaceutically acceptable salt thereof. In some embodiments, the API is alectinib hydrochloride.

[0223] In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof (such as alectinib hydrochloride), wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is from about 3% to about 60% by weight of ASD. In some embodiments, the alectinib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at about 10% to about 50% by weight. In some embodiments, the alectinib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at about 15% to about 30% by weight. In some embodiments, the alectinib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at about 25% to about 40% by weight. In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is from about 3% to about 30% by weight of ASD. In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 25% by weight of ASD. In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 20% by weight of ASD. In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is about 10% by weight of ASD. In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is about 20% by weight of ASD.

[0224] In some embodiments, the free base of alectinib or a pharmaceutically acceptable salt thereof (such as alectinib hydrochloride) is present in the amorphous solid dispersion at a weight percentage of about 5% to about 60%. In some embodiments, the free base of alectinib or a pharmaceutically acceptable salt thereof is present at a weight percentage of about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 5% to about 35%, about 5% to about 40%, about 5% to about 45%, about 5% to about 50%, about 5% to about 55%, about 5% to about 60%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%. %, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% The alectinib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion at a weight percentage of about 60%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 50% to about 55%, about 50% to about 60%, or about 55% to about 60%. In some embodiments, the alectinib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion at a weight percentage of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, the alectinib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion at a weight percentage of at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or about 55%.In some embodiments, the alectinib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion in weight percentages of up to about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%.

[0225] In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is nonionic. In some embodiments, the hydrophilic polymer is ionic. In some embodiments, the hydrophilic polymer is an enteric polymer. In some embodiments, the pharmaceutical composition described herein comprises ASD, which comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the hydrophilic polymer is polymethacrylate. In some embodiments, the hydrophilic polymer is HPMCAS HPMC. In some embodiments, the hydrophilic polymer is Soluplus. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, HPMCAS, or Soluplus or a combination thereof. In some embodiments, the hydrophilic polymer comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters (e.g., Labrasol or Gelucire), polysorbate, or a combination thereof. In some embodiments, the hydrophilic polymer is present in an amount of about 1% to about 80% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 5% to about 70% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 10% to about 60% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% to about 50% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% to about 40% by weight of ASD.

[0226] In some embodiments, ASD optionally includes a surfactant. In some embodiments, ASD optionally includes a surfactant. In some embodiments, the surfactant is TPGS. In some embodiments, the surfactant is polyoxyethylene glycerol ester. In some embodiments, the surfactant is SLS. In some embodiments, the surfactant is polysorbate ester. In some embodiments, the surfactant is polyoxyethylene hydrogenated castor oil. In some embodiments, the surfactant is TPGS, polyoxyethylene glycerol ester, polysorbate ester, polyoxyethylene hydrogenated castor oil, or SLS or a combination thereof. In some embodiments, the surfactant is present in an amount from about 5% by weight to about 60% by weight of ASD. In some embodiments, the surfactant is present in an amount from about 5% by weight to about 40% by weight of ASD. In some embodiments, the surfactant is present in an amount from about 5% by weight to about 30% by weight of ASD.

[0227] In some embodiments, ASD optionally includes an adsorbent. In some embodiments, the adsorbent is silica. In some embodiments, the adsorbent is present in an amount of about 1% by weight to about 40% by weight of ASD.

[0228] In some embodiments, ASD contains optionally an inorganic acid or an organic acid. In some embodiments, ASD contains optionally an organic acid. In some embodiments, ASD contains an organic acid. In some embodiments, the organic acid is tartaric acid. In some embodiments, the organic acid is citric acid. In some embodiments, the organic acid is malic acid. In some embodiments, the organic acid is tartaric acid, citric acid, or malic acid, or a combination thereof. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 40% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 10% by weight to about 50% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 30% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 20% by weight of ASD.

[0229] In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 60% by weight of ASD. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 15% by weight to about 80% by weight of ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethyl methacrylate, HPMCAS, or Soluplus, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 10% by weight to about 40% by weight of ASD. In some embodiments, the surfactant is TPGS or SLS, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 10% by weight to about 50% by weight of ASD. In some embodiments, the organic acid is tartaric acid.

[0230] In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, said alectinib free base or a pharmaceutically acceptable salt thereof, in an amount of about 15% to about 55% by weight of ASD. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is in an amount of about 15% to about 70% by weight of ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, HPMCAS, or Soluplus, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the surfactant is in an amount of about 15% to about 30% by weight of ASD. In some embodiments, the surfactant is TPGS, polyoxyethylene glycerol ester, polysorbate, polyoxyethylene hydrogenated castor oil, or SLS, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the organic acid is in an amount of about 20% to about 40% by weight of ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, ASD comprises an adsorbent, said adsorbent in an amount of about 1% to 40% by weight of ASD. In some embodiments, the adsorbent is silica.

[0231] In some embodiments, the pharmaceutical compositions described herein comprise ASD, said ASD comprising alectinib free base or a pharmaceutically acceptable salt thereof (such as alectinib hydrochloride), said alectinib free base or a pharmaceutically acceptable salt thereof in an amount of about 25% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer in an amount of about 50% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMCAS. In some embodiments, the ASD comprises a surfactant. In some embodiments, the surfactant in an amount of about 25% by weight of the ASD. In some embodiments, the surfactant is SLS. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the adsorbent in an amount of about 1% to 30% by weight of the ASD. In some embodiments, the adsorbent is silica.

[0232] In some embodiments, the pharmaceutical composition described herein comprises an ASD, which comprises alectinib free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of alectinib free base or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 50% by weight of the ASD. In some embodiments, the amount of alectinib free base or a pharmaceutically acceptable salt thereof is from about 10-30% by weight of the ASD. In some embodiments, the amount of alectinib free base or a pharmaceutically acceptable salt thereof is from about 10-25% by weight of the ASD. In some embodiments, the amount of alectinib free base or a pharmaceutically acceptable salt thereof is from about 15% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 80% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 5% by weight to about 70% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 15% by weight to about 60% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 25% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC, HPMCAS, polyvinyl acetate, a polyvinylcaprolactam-based graft copolymer, PVP, copovidone, polymethacrylate, or a combination thereof. In some embodiments, the hydrophilic polymer is eudragit. In some embodiments, the hydrophilic polymer is lauroyl polyoxyethylene-32 glycerol. In some embodiments, the hydrophilic polymer is HPMC-E5. In some embodiments, the hydrophilic polymer is HPMCAS-LF. In some embodiments, the ASD contains a surfactant. In some embodiments, the amount of surfactant is from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the amount of surfactant is from about 10% by weight to about 40% by weight of the ASD. In some embodiments, the amount of surfactant is from about 10% by weight to about 30% by weight of the ASD. In some embodiments, the amount of surfactant is from about 20% by weight to about 25% by weight of the ASD. In some embodiments, the surfactant is TPGS. In some embodiments, TPGS is present in an amount of about 20-25% by weight of the ASD. In some embodiments, the surfactant is SDS. In some embodiments, SDS is present in an amount of about 15% by weight to about 40% by weight of the ASD. In some embodiments, the surfactant is RH40. In some embodiments, the surfactant comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters, polysorbate esters, or combinations thereof. In some embodiments, RH40 is present in an amount of about 20% by weight of ASD. In some embodiments, the surfactant is Tween-20.In some embodiments, Tween-20 is present in an amount of about 20% by weight of ASD. In some embodiments, the surfactant is Gelucire 44 / 14. In some embodiments, Gelucire 44 / 14 is present in an amount of about 20% by weight of ASD. In some embodiments, ASD comprises an organic acid. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 35% by weight of ASD. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 30% by weight of ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, tartaric acid is present in an amount of about 20% by weight to 25% by weight of ASD. In some embodiments, ASD comprises an adsorbent. In some embodiments, the adsorbent is present in an amount of about 15% by weight to about 40% by weight of ASD. In some embodiments, the adsorbent is SiO2. In some embodiments, SiO2 is present in an amount of about 20% by weight of ASD.

[0233] In some embodiments, the pharmaceutical composition described herein comprises an ASD comprising: alectinib free base or a pharmaceutically acceptable salt thereof, the amount of the alectinib free base or a pharmaceutically acceptable salt thereof being about 25% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being about 75% by weight of the ASD, and wherein the hydrophilic polymer is Eudagrit L100-55 or HPMC-E5.

[0234] In some embodiments, the pharmaceutical composition described herein comprises an ASD consisting of: an alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is from about 10% to about 30% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 20% to about 75% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS, Soluplus, or HPMC-E5; and a surfactant, wherein the amount of the surfactant is from about 10% to about 25% by weight of the ASD, wherein the surfactant is TPGS, SDS, or lecithin.

[0235] In some embodiments, the pharmaceutical composition described herein comprises ASD, said ASD consisting of: alectinib free base or a pharmaceutically acceptable salt thereof, said alectinib free base or a pharmaceutically acceptable salt thereof in an amount of about 20% to 25% by weight of ASD; a hydrophilic polymer in an amount of about 15% to 25% by weight of ASD, wherein the hydrophilic polymer is HPMCAS, HPMC-E5 or Eudragit L100; and tartaric acid in an amount of about 25% to 30% by weight of ASD.

[0236] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the alectinib free base or a pharmaceutically acceptable salt thereof is about 20% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is about 20% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS-LF; and a surfactant, wherein the amount of the surfactant is about 10% to 25% by weight of the ASD, wherein the surfactant is TPGS, Tween-20, Gelcure 44 / 14, RH40, SDS, or a combination thereof; tartaric acid, wherein the amount of the tartaric acid is about 20% by weight of the ASD; and an adsorbent, wherein the amount of the adsorbent is about 20% by weight of the ASD, wherein the adsorbent is SiO2.

[0237] In some embodiments, ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof, said alectinib free base or a pharmaceutically acceptable salt thereof in an amount of about 50 mg to about 200 mg. In some embodiments, ASD comprises a hydrophilic polymer in an amount of about 100 mg to about 500 mg. In some embodiments, the hydrophilic polymer is HPMC, HPMCAs, or Soluplus or a combination thereof. In some embodiments, ASD comprises a surfactant in an amount of about 40 mg to about 250 mg. In some embodiments, the surfactant is TPGS or SLS or a combination thereof. In some embodiments, ASD comprises an organic acid in an amount of about 70 mg to 250 mg. In some embodiments, the organic acid is tartaric acid. In some embodiments, ASD comprises an adsorbent in an amount of about 20 mg to 300 mg by weight of ASD. In some embodiments, the adsorbent is silica. In some embodiments, the pharmaceutical compositions comprising ASD described herein are formulated in unit dosage forms.

[0238] In some embodiments, ASD comprises: alectinib free base or a pharmaceutically acceptable salt thereof, said alectinib free base or a pharmaceutically acceptable salt thereof in an amount of about 60 mg to about 180 mg; a hydrophilic polymer in an amount of about 100 mg to about 400 mg. In some embodiments, the hydrophilic polymer is HPMC, HPMCAs, or Soluplus or a combination thereof; a surfactant in an amount of about 50 mg to about 200 mg. In some embodiments, the surfactant is TPGS or SLS or a combination thereof; and optionally an organic acid in an amount of about 130 mg to 180 mg. In some embodiments, the organic acid is tartaric acid. In some embodiments, ASD comprises an adsorbent in an amount of about 50 mg to 200 mg by weight of ASD. In some embodiments, the adsorbent is silica. In some embodiments, the pharmaceutical compositions comprising ASD described herein are formulated in unit dosage forms.

[0239] In some embodiments, the pharmaceutical compositions comprising an ASD described herein have acceptable storage stability, wherein the ASD comprises alectinib free base or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical compositions are stable at 75°C / 75% RH for at least 2 weeks, wherein the chemically stable pharmaceutical compositions exhibit less than 5% degradation of the API at the end of the storage period. In some embodiments, the pharmaceutical compositions are stable at 40°C / 75% RH for at least 6 months, wherein the stable pharmaceutical compositions have less than 0.5% of any impurities at the end of the storage period. In some embodiments, the pharmaceutical compositions are stable at 25°C / 60% RH for at least 2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months, or 24 months, wherein the stable pharmaceutical compositions have less than 0.5% of any impurities at the end of the storage period.

[0240] In some embodiments, when administered orally, the AUC, AUC inf or AUC last When measured, the bioavailability of the pharmaceutical composition described herein is superior to that of a corresponding reference composition containing alectinib hydrochloride. In some embodiments, when measured after oral administration, the bioavailability is measured in AUC, AUCinf, or AUC. last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing alectinib hydrochloride. In some embodiments, when administered orally, Cmax When measured, the bioavailability of the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing alectinib hydrochloride.

[0241] In some embodiments, when administered orally, the AUC, AUC inf or AUC last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of ALECENSA capsules containing alectinib hydrochloride. In some embodiments, when administered orally, C maxWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of ALECENSA capsules containing alectinib hydrochloride. In some embodiments, the bioavailability exhibited by the pharmaceutical compositions is about 1.1 to about 10 times higher than that of ALECENSA. In some embodiments, the bioavailability of the pharmaceutical composition is about 1.1 times to about 2 times, about 1.1 times to about 3 times, about 1.1 times to about 4 times, about 1.1 times to about 5 times, about 1.1 times to about 6 times, about 1.1 times to about 7 times, about 1.1 times to about 8 times, about 1.1 times to about 10 times, about 1.5 times to about 2 times, about 1.5 times to about 3 times, about 1.5 times to about 4 times, about 1.5 times to about 5 times, about 1.5 times to about 6 times, about 1.5 times to about 7 times, about 1.5 times to about 8 times, about 1.5 times to about 10 times, about 2 times to about 4 times, about 2 times Up to 5 times, about 2 times to 6 times, about 2 times to 7 times, about 2 times to 8 times, about 2 times to 10 times, about 3 times to 4 times, about 3 times to 5 times, about 3 times to 6 times, about 3 times to 7 times, about 3 times to 8 times, about 3 times to 10 times, about 4 times to 5 times, about 4 times to 6 times, about 4 times to 7 times, about 4 times to 8 times, about 4 times to 10 times, about 5 times to 6 times, about 5 times to 7 times, about 5 times to 8 times, about 5 times to 10 times, about 6 times to 7 times, about 6 times to 8 times, about 6 times to 10 times, about 7 times to 8 times, about 7 times to 10 times, or about 8 times to 10 times. In some embodiments, the pharmaceutical composition comprises ASD, said ASD comprising alectinib or a salt thereof (such as alectinib hydrochloride). In some embodiments, bioavailability is measured under fasting conditions.

[0242] In some embodiments, when administered orally at AUC last Or C maxWhen measured, the pharmaceutical compositions described herein exhibit bioavailability that is at least about 1.1 times, about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, or about 8 times higher than the bioavailability of ALECENSA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 2 times higher than the bioavailability of ALECENSA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 4 times higher than the bioavailability of ALECENSA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at most about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, or about 10 times higher than the bioavailability of ALECENSA. In some embodiments, bioavailability is measured in a canine model under fasting conditions. In some embodiments, bioavailability is measured in a canine model under feeding conditions. In some embodiments, AUC is measured after oral administration. last When the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, when administered orally with C max During measurement, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 40%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 20%. In some embodiments, bioavailability is measured in a canine model. In some embodiments, the canine model is a beagle. In some embodiments, bioavailability is measured under fasting conditions. In some embodiments, bioavailability is measured under feeding conditions. In some embodiments, the pharmaceutical composition comprises an ASD comprising alectinib free base or a pharmaceutically acceptable salt thereof (such as alectinib hydrochloride).

[0243] In some embodiments, when administered orally at AUC last Or C maxWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is about 30% to about 1500%, 40% to about 1000%, 50% to about 500%, about 70% to about 300%, 75% to about 200%, or about 80% to about 150% of the bioavailability of a corresponding reference composition containing alectinib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, the dose of the reference composition is at least about 1.1 times the dose of the pharmaceutical composition. In some embodiments, the dose of the reference composition is at least about 1.1 times, about 1.5 times, about 2 times, about 2.5 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, or about 10 times the dose of the pharmaceutical composition. In some embodiments, the pharmaceutical composition contains an ASD, said ASD comprising alectinib free base or a pharmaceutically acceptable salt thereof (such as alectinib hydrochloride). In some embodiments, the reference composition comprises alectinib free base or a pharmaceutically acceptable salt thereof, wherein the reference composition does not contain ASD. In some embodiments, the reference composition is ALECENSA. In some embodiments, bioavailability is measured under fasting conditions. In some embodiments, bioavailability is measured under feeding conditions. In some embodiments, bioavailability is measured under feeding conditions.

[0244] In some embodiments, when administered orally at AUC last When measured, the bioavailability of the pharmaceutical compositions described herein is about 75% to about 200% of the bioavailability of a corresponding reference composition containing alectinib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is at least 1.75 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is ALECENSA. In some embodiments, bioavailability is measured under fasting conditions.

[0245] In some embodiments, when administered orally with C max When measured, the bioavailability of the pharmaceutical compositions described herein is about 75% to about 200% of the bioavailability of a corresponding reference composition containing alectinib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is at least 1.75 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is ALECENSA. In some embodiments, bioavailability is measured under fasting conditions. In some embodiments, bioavailability is measured under eating conditions.

[0246] In some embodiments, after oral administration under fasting conditions, the AUC is measured. lastWhen measured, the bioavailability of the pharmaceutical compositions described herein is at least about 110% of the bioavailability of a corresponding reference composition containing alectinib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about twice the dose of the pharmaceutical composition. In some embodiments, after oral administration under fasting conditions, the bioavailability is measured at AUC. last When measured, the bioavailability of the pharmaceutical compositions described herein is at least about 80% of the bioavailability of a corresponding reference composition containing alectinib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about twice the dose of the pharmaceutical composition. In some embodiments, the reference composition is ALECENSA.

[0247] In some embodiments, after oral administration under fasting conditions, C max When measured, the bioavailability of the pharmaceutical compositions described herein is at least about 110% of the bioavailability of a corresponding reference composition containing alectinib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about twice the dose of the pharmaceutical composition. In some embodiments, after oral administration under food conditions, C max When measured, the bioavailability of the pharmaceutical compositions described herein is at least about 80% of the bioavailability of a corresponding reference composition containing alectinib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about twice the dose of the pharmaceutical composition. In some embodiments, the reference composition is ALECENSA.

[0248] In some embodiments, salts of the alectinib compound are formed, for example, by alectinib with a compound containing a basic nitrogen atom as an acid addition salt (e.g., having an organic or inorganic acid), such as pharmaceutically acceptable salts. Suitable inorganic acids are, for example, hydrohalic acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, for example, carboxylic acids, phosphonic acids, sulfonic acids or aminosulfonic acids, acetic acid, propionic acid, octanoic acid, decanoic acid, dodecanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, octanoic acid, azelaic acid, malic acid, tartaric acid, citric acid, amino acids such as glutamic acid or aspartic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, cyclohexanecarboxylic acid, adamantanecarboxylic acid, benzoic acid, salicylic acid, 4-aminosalicylic acid, phthalic acid, etc. Dicarboxylic acid, phenylacetic acid, mandelic acid, cinnamic acid, methane- or ethane-sulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 1,5-naphthalene-disulfonic acid, 2-, 3- or 4-methylbenzenesulfonic acid, methylsulfuric acid, ethylsulfuric acid, dodecyl sulfate, N-cyclohexylaminosulfonic acid, N-methyl-, N-ethyl- or N-propyl-aminosulfonic acid, or other organic protic acids, such as ascorbic acid.

[0249] e) Pazopanib hydrochloride

[0250] On one hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API, a hydrophilic polymer, a surfactant, optionally an organic acid, and optionally an adsorbent. On the other hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API. In some embodiments, the API is a free base of pazopanib or a pharmaceutically acceptable salt thereof. In some embodiments, the API is pazopanib hydrochloride.

[0251] In some embodiments, ASD comprises a free base of pazopanib or a pharmaceutically acceptable salt thereof (such as pazopanib hydrochloride), wherein the amount of the free base of pazopanib or a pharmaceutically acceptable salt thereof is from about 3% to about 60% by weight of ASD. In some embodiments, the free base of pazopanib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 10% to about 50%. In some embodiments, the free base of pazopanib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 15% to about 30%. In some embodiments, the free base of pazopanib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 25% to about 40%. In some embodiments, ASD comprises a free base of pazopanib or a pharmaceutically acceptable salt thereof, wherein the amount of the free base of pazopanib or a pharmaceutically acceptable salt thereof is from about 3% to about 50% by weight of ASD. In some embodiments, ASD comprises pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 40% by weight of ASD. In some embodiments, ASD comprises pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 30% by weight of ASD. In some embodiments, ASD comprises pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 18.2% by weight of ASD. In some embodiments, ASD comprises pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 20% by weight of ASD. In some embodiments, ASD comprises pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 25% by weight of ASD.

[0252] In some embodiments, the free base of pazopanib or a pharmaceutically acceptable salt thereof (such as pazopanib hydrochloride) is present in the amorphous solid dispersion at a weight percentage of about 5% to about 60%. In some embodiments, the free base of pazopanib or a pharmaceutically acceptable salt thereof is present at a weight percentage of about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 5% to about 35%, about 5% to about 40%, about 5% to about 45%, about 5% to about 50%, about 5% to about 55%, about 5% to about 60%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%. %, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% The amorphous solids are present in the dispersion at a weight percentage of about 60%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 50% to about 55%, about 50% to about 60%, or about 55% to about 60%. In some embodiments, the free base of pazopanib or a pharmaceutically acceptable salt thereof (such as pazopanib hydrochloride) is present in the amorphous solids dispersion at a weight percentage of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, the free base of pazopanib or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or about 55%.In some embodiments, the pazopanib free base or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion in up to about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60% by weight.

[0253] In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is nonionic. In some embodiments, the hydrophilic polymer is ionic. In some embodiments, the hydrophilic polymer is an enteric polymer. In some embodiments, the pharmaceutical composition described herein comprises ASD, which comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the hydrophilic polymer is polymethacrylate. In some embodiments, the hydrophilic polymer is a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam. In some embodiments, the hydrophilic polymer is PVP. In some embodiments, the hydrophilic polymer is copovidone. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, HPMCS, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, the hydrophilic polymer comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters (e.g., Labrasol or Gelucire), polysorbate, or combinations thereof. In some embodiments, the hydrophilic polymer is present in an amount of about 1% to about 80% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 5% to about 70% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 10% to about 60% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% to about 50% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% to about 40% by weight of ASD.

[0254] In some embodiments, the ASD optionally includes a surfactant. In some embodiments, the surfactant includes phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters, polysorbate esters, or combinations thereof. In some embodiments, the surfactant includes lecithin and TPGS. In some embodiments, the surfactant includes lecithin. In some embodiments, the surfactant includes PEG. In some embodiments, the surfactant includes block copolymers of polyethylene glycol and polypropylene glycol. In some embodiments, the surfactant includes SLS. In some embodiments, the surfactant includes graft copolymers based on polyvinyl acetate and polyvinylcaprolactam. In some embodiments, the surfactant includes polyoxyethylene hydrogenated castor oil (e.g., sold under the trade name RH40). In some embodiments, the surfactant includes polysorbate esters. In some embodiments, the surfactant includes polyoxyethylene glycerol esters (e.g., Labrasol or Gelucire). In some embodiments, the surfactant includes TPGS. In some embodiments, the surfactant is present in an amount of about 5% by weight to about 60% by weight of the ASD. In some embodiments, the surfactant is present in an amount of about 5% to about 40% by weight of ASD. In some embodiments, the surfactant is present in an amount of about 5% to about 30% by weight of ASD.

[0255] In some embodiments, ASD optionally includes an adsorbent. In some embodiments, the adsorbent is silica. In some embodiments, the adsorbent is present in an amount of about 15% by weight to about 40% by weight of ASD.

[0256] In some embodiments, ASD contains optionally an inorganic acid or an organic acid. In some embodiments, ASD contains optionally an organic acid. In some embodiments, ASD contains an organic acid, wherein the organic acid is tartaric acid. In some embodiments, the inorganic acid or organic acid is present in an amount from about 10% by weight to about 40% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 30% by weight of ASD. In some embodiments, the inorganic acid or organic acid is present in an amount from about 1% by weight to about 20% by weight of ASD.

[0257] In some embodiments, the ASD comprises an adsorbent. In some embodiments, the adsorbent is SiO2. In some embodiments, the adsorbent is present in an amount of about 10% to about 40% by weight of the ASD. In some embodiments, the adsorbent is present in an amount of about 1% to about 30% by weight of the ASD. In some embodiments, the adsorbent is present in an amount of about 1% to about 20% by weight of the ASD.

[0258] In some embodiments, the ASD comprises a free base of pazopanib or a pharmaceutically acceptable salt thereof (such as pazopanib hydrochloride). In some embodiments, the amount of the free base of pazopanib or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 50% by weight of the ASD. In some embodiments, the amount of the free base of pazopanib or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 40% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 5% by weight to about 70% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 70% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 40% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 10% by weight to about 30% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, the hydrophilic polymer comprises HPMC, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, polymethacrylate, or combinations thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the amount of the surfactant is from about 10% by weight to about 40% by weight of the ASD. In some embodiments, the surfactant comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol, polysorbate, or combinations thereof. In some embodiments, the surfactant is TPGS or lecithin or combinations thereof. In some embodiments, the surfactant comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters, polysorbate esters, or combinations thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 10% by weight to about 40% by weight of the ASD. In some embodiments, the amount of the organic acid is from about 10% by weight to about 35% by weight of the ASD. In some embodiments, the amount of the organic acid is from about 10% by weight to about 30% by weight of the ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 15% by weight to about 40% by weight of the ASD. In some embodiments, the adsorbent is SiO2.

[0259] In some embodiments, ASD comprises a pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of the pazopanib free base or a pharmaceutically acceptable salt thereof is from about 15% to about 30% by weight of ASD. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 15% to about 60% by weight of ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 15% to about 30% by weight of ASD. In some embodiments, the surfactant is TPGS or lecithin, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 15% to about 30% by weight of ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 20% to about 35% by weight of ASD. In some embodiments, the adsorbent is SiO2.

[0260] In some embodiments, the pharmaceutical compositions described herein comprise ASD, said ASD comprising pazopanib free base or a pharmaceutically acceptable salt thereof, said pazopanib free base or a pharmaceutically acceptable salt thereof in an amount of about 15-20% by weight of ASD. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer in an amount of about 15-20% by weight of ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the surfactant in an amount of about 15-20% by weight of ASD. In some embodiments, the surfactant is TPGS. In some embodiments, ASD comprises an organic acid. In some embodiments, the organic acid in an amount of about 15-20% by weight of ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, ASD comprises an adsorbent. In some embodiments, the adsorbent in an amount of about 25-30% by weight of ASD. In some embodiments, the adsorbent is SiO2.

[0261] In some embodiments, the pharmaceutical compositions described herein comprise ASD, which comprises pazopanib free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 10-30% by weight of the ASD. In some embodiments, the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 15-20% by weight of the ASD. In some embodiments, the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 16% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is about 10% by weight to about 30% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 10% by weight to about 20% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 15% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC, HPMCAs, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, the hydrophilic polymer is HPMC-E5. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the ASD contains a surfactant. In some embodiments, the amount of surfactant is from about 10% to about 40% by weight of the ASD. In some embodiments, the amount of surfactant is from about 20% to about 40% by weight of the ASD. In some embodiments, the amount of surfactant is from about 30% by weight of the ASD. In some embodiments, the surfactant is TPGS or lecithin or a combination thereof. In some embodiments, TPGS is present in an amount of about 15% by weight of the ASD. In some embodiments, lecithin is present in an amount of about 15% by weight of the ASD. In some embodiments, the ASD contains an organic acid. In some embodiments, the organic acid is present in an amount of from about 10% to about 30% by weight of the ASD. In some embodiments, the organic acid is present in an amount of from about 10% to about 20% by weight of the ASD. In some embodiments, the organic acid is present in an amount of about 15% by weight of the ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, the ASD contains an adsorbent. In some embodiments, the adsorbent is present in an amount of from about 15% to about 40% by weight of the ASD. In some embodiments, the adsorbent is present in an amount of about 20% to about 30% by weight of ASD. In some embodiments, the adsorbent is present in an amount of about 23% by weight of ASD. In some embodiments, the adsorbent is SiO2.

[0262] In some embodiments, the pharmaceutical composition described herein comprises ASD, the ASD comprising: pazopanib free base or a pharmaceutically acceptable salt thereof, the amount of the pazopanib free base or a pharmaceutically acceptable salt thereof being about 16% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being about 15% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5; TPGS, the amount of the TPGS being about 15% by weight of the ASD; lecithin, the amount of the lecithin being about 15% by weight of the ASD; tartaric acid, the amount of the tartaric acid being about 15% by weight of the ASD; and an adsorbent, the amount of the adsorbent being about 23% by weight of the ASD, wherein the adsorbent is SiO2.

[0263] In some embodiments, the pharmaceutical composition described herein comprises ASD, the ASD consisting of: a pazopanib free base or a pharmaceutically acceptable salt thereof, the amount of the pazopanib free base or a pharmaceutically acceptable salt thereof being from about 10% to about 30% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being from about 10% to about 30% by weight of the ASD, wherein the hydrophilic polymer is HPMC, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof; a surfactant, the amount of the surfactant being from about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, lecithin, or a combination thereof; an organic acid, the amount of the organic acid being from about 10% to about 30% by weight of the ASD, wherein the organic acid is tartaric acid; and optionally an adsorbent, the amount of the adsorbent being from about 15% to about 40% by weight of the ASD, wherein the adsorbent is SiO2.

[0264] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 16% by weight of ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is about 15% by weight of ASD, wherein the hydrophilic polymer is HPMC-E5; TPGS, wherein the amount of TPGS is about 15% by weight of ASD; lecithin, wherein the amount of lecithin is about 15% by weight of ASD; tartaric acid, wherein the amount of tartaric acid is about 15% by weight of ASD; and an adsorbent, wherein the amount of the adsorbent is about 23% by weight of ASD, wherein the adsorbent is SiO2.

[0265] In some embodiments, the ASD comprises a free base of pazopanib or a pharmaceutically acceptable salt thereof (e.g., pazopanib hydrochloride), said free base of pazopanib or a pharmaceutically acceptable salt thereof, in an amount of about 30 mg to about 200 mg. In some embodiments, the ASD comprises a hydrophilic polymer / in some embodiments, the amount of the hydrophilic polymer is about 30 mg to about 400 mg. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is about 30 mg to about 200 mg. In some embodiments, the surfactant is TPGS or lecithin, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is about 30 mg to 200 mg. In some embodiments, the organic acid is tartaric acid. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is about 30 mg to about 150 mg. In some embodiments, the adsorbent is SiO2. In some embodiments, the pharmaceutical compositions comprising ASD described herein are dispensed in unit dosage forms.

[0266] In some embodiments, the ASD comprises a free base of pazopanib or a pharmaceutically acceptable salt thereof (e.g., pazopanib hydrochloride), wherein the amount of the free base of pazopanib or a pharmaceutically acceptable salt thereof is from about 30 mg to about 150 mg. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 30 mg to about 300 mg. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, or a combination thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 30 mg to about 150 mg. In some embodiments, the surfactant is TPGS or lecithin, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 30 mg to 150 mg. In some embodiments, the organic acid is tartaric acid. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 40 mg to about 100 mg. In some embodiments, the adsorbent is SiO2. In some embodiments, the pharmaceutical compositions comprising ASD described herein are dispensed in unit dosage forms.

[0267] In some embodiments, the pharmaceutical compositions comprising an ASD described herein have acceptable storage stability, wherein the ASD comprises a free base of pazopanib or a pharmaceutically acceptable salt thereof (e.g., pazopanib hydrochloride). In some embodiments, the pharmaceutical compositions are chemically stable at 75°C / 75% RH for at least 2 weeks, wherein the degradation of the API in the storage-stable pharmaceutical compositions is less than 5% at the end of the storage period. In some embodiments, the pharmaceutical compositions are stable at 40°C / 75% RH for at least 6 months, wherein the storage-stable pharmaceutical compositions have less than 0.5% of any impurities at the end of the storage period. In some embodiments, the pharmaceutical compositions are stable at 25°C / 60% RH for at least 2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months, or 24 months, wherein the storage-stable pharmaceutical compositions have less than 0.5% of any impurities at the end of the storage period.

[0268] In some embodiments, when administered orally, the AUC, AUC inf or AUC last When measured, the bioavailability of the pharmaceutical composition described herein is superior to that of the corresponding reference composition containing pazopanib hydrochloride. In some embodiments, when measured after oral administration, the bioavailability is measured in AUC, AUCinf, or AUC. last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing pazopanib hydrochloride. In some embodiments, when administered orally, C max When measured, the bioavailability of the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing pazopanib hydrochloride.

[0269] In some embodiments, when administered orally, the AUC, AUC inf or AUC lastWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of VOTRIENT capsules containing pazopanib hydrochloride. In some embodiments, when administered orally, C max When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of VOTRIENT capsules containing pazopanib hydrochloride. In some embodiments, the bioavailability exhibited by the pharmaceutical compositions is about 1.1 to about 10 times higher than that of VOTRIENT. In some embodiments, the bioavailability of the pharmaceutical composition is about 1.1 times to about 2 times, about 1.1 times to about 3 times, about 1.1 times to about 4 times, about 1.1 times to about 5 times, about 1.1 times to about 6 times, about 1.1 times to about 7 times, about 1.1 times to about 8 times, about 1.1 times to about 10 times, about 1.5 times to about 2 times, about 1.5 times to about 3 times, about 1.5 times to about 4 times, about 1.5 times to about 5 times, about 1.5 times to about 6 times, about 1.5 times to about 7 times, about 1.5 times to about 8 times, about 1.5 times to about 10 times, about 2 times to about 4 times, about 2 times The bioavailability is approximately 5 times, approximately 2 times to approximately 6 times, approximately 2 times to approximately 7 times, approximately 2 times to approximately 8 times, approximately 2 times to approximately 10 times, approximately 3 times to approximately 4 times, approximately 3 times to approximately 5 times, approximately 3 times to approximately 6 times, approximately 3 times to approximately 7 times, approximately 3 times to approximately 8 times, approximately 3 times to approximately 10 times, approximately 4 times to approximately 5 times, approximately 4 times to approximately 6 times, approximately 4 times to approximately 7 times, approximately 4 times to approximately 8 times, approximately 4 times to approximately 10 times, approximately 5 times to approximately 6 times, approximately 5 times to approximately 7 times, approximately 5 times to approximately 8 times, approximately 5 times to approximately 10 times, approximately 6 times to approximately 7 times, approximately 6 times to approximately 8 times, approximately 6 times to approximately 10 times, approximately 7 times to approximately 8 times, approximately 7 times to approximately 10 times, or approximately 8 times to approximately 10 times. In some embodiments, the pharmaceutical composition comprises an ASD, said ASD comprising pazopanib or pazopanib hydrochloride. In some embodiments, bioavailability is measured under fasting conditions.

[0270] In some embodiments, when administered orally at AUC last Or C maxWhen measured, the pharmaceutical compositions described herein exhibit bioavailability that is at least about 1.1 times, about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, or about 8 times higher than the bioavailability of VOTRIENT. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 2 times higher than the bioavailability of VOTRIENT. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 4 times higher than the bioavailability of VOTRIENT. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at most about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, or about 10 times higher than the bioavailability of VOTRIENT. In some embodiments, bioavailability is measured in a canine model under fasting conditions. In some embodiments, bioavailability is measured in a canine model under feeding conditions. In some embodiments, AUC is measured after oral administration. last When the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, when administered orally with C max During measurement, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%, 40%, 30%, 20%, 15%, or 10%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 50%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 40%. In some embodiments, the bioavailability of the pharmaceutical composition administered orally in a fed state differs from that administered in a fasted state by no more than 20%. In some embodiments, bioavailability is measured in a canine model. In some embodiments, the canine model is a beagle. In some embodiments, bioavailability is measured under fasting conditions. In some embodiments, bioavailability is measured under feeding conditions. In some embodiments, the pharmaceutical composition comprises an ASD comprising a free base of pazopanib or a pharmaceutically acceptable salt thereof (e.g., pazopanib hydrochloride).

[0271] In some embodiments, when administered orally at AUC last Or C maxWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is about 25% to about 1500%, 30% to about 1000%, 35% to about 500%, about 40% to about 300%, 40% to about 200%, or about 50% to about 120% of the bioavailability of a corresponding reference composition containing pazopanib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion. In some embodiments, the dose of the reference composition is at least about 1.1 times the dose of the pharmaceutical composition. In some embodiments, the dose of the reference composition is at least about 1.1 times, about 1.5 times, about 2 times, about 2.5 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, or about 10 times the dose of the pharmaceutical composition. In some embodiments, the pharmaceutical composition contains an ASD comprising a free base of pazopanib or a pharmaceutically acceptable salt thereof (e.g., pazopanib hydrochloride). In some embodiments, the reference composition comprises a free base of pazopanib or a pharmaceutically acceptable salt thereof, wherein the reference composition does not contain ASD. In some embodiments, the reference composition is VOTRIENT. In some embodiments, bioavailability is measured under fasting conditions. In some embodiments, bioavailability is measured under feeding conditions. In some embodiments, bioavailability is measured under feeding conditions.

[0272] In some embodiments, after oral administration under fasting conditions, the AUC is measured. last When measured, the bioavailability of the pharmaceutical compositions described herein is about 40% to about 100% of the bioavailability of a corresponding reference composition containing pazopanib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is at least 3 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is VOTRIENT. In some embodiments, bioavailability is measured under fasting conditions.

[0273] In some embodiments, after oral administration under fasting conditions, C max When measured, the bioavailability of the pharmaceutical compositions described herein is about 50% to about 120% of the bioavailability of a corresponding reference composition containing pazopanib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is at least 3 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is VOTRIENT. In some embodiments, bioavailability is measured under fasting conditions.

[0274] In some embodiments, after oral administration under fasting conditions, the AUC is measured. lastWhen measured, the bioavailability of the pharmaceutical compositions described herein is at least about 50% of the bioavailability of a corresponding reference composition containing pazopanib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about 4 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is VOTRIENT. In some embodiments, bioavailability is measured under fasting conditions.

[0275] In some embodiments, after oral administration under fasting conditions, C max When measured, the bioavailability of the pharmaceutical compositions described herein is at least about 70% of the bioavailability of a corresponding reference composition containing pazopanib hydrochloride, wherein the corresponding reference pharmaceutical composition does not contain an amorphous solid dispersion, and wherein the dose of the reference composition is about 4 times the dose of the pharmaceutical composition. In some embodiments, the reference composition is VOTRIENT. In some embodiments, bioavailability is measured under fasting conditions.

[0276] In some embodiments, salts of pazopanib compounds are formed by, for example, pazopanib with a compound containing a basic nitrogen atom as an acid addition salt (e.g., having an organic or inorganic acid), such as pharmaceutically acceptable salts. Suitable inorganic acids are, for example, hydrohalic acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, for example, carboxylic acids, phosphonic acids, sulfonic acids or aminosulfonic acids, acetic acid, propionic acid, octanoic acid, decanoic acid, dodecanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, octanoic acid, azelaic acid, malic acid, tartaric acid, citric acid, amino acids such as glutamic acid or aspartic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, cyclohexanecarboxylic acid, adamantanecarboxylic acid, benzoic acid, salicylic acid, 4-aminosalicylic acid, phthalic acid, etc. Dicarboxylic acid, phenylacetic acid, mandelic acid, cinnamic acid, methane- or ethane-sulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 1,5-naphthalene-disulfonic acid, 2-, 3- or 4-methylbenzenesulfonic acid, methylsulfuric acid, ethylsulfuric acid, dodecyl sulfate, N-cyclohexylaminosulfonic acid, N-methyl-, N-ethyl- or N-propyl-aminosulfonic acid, or other organic protic acids, such as ascorbic acid.

[0277] f) Lurasidone hydrochloride

[0278] On one hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API, a hydrophilic polymer, a surfactant, optionally an organic acid, and optionally an adsorbent. On the other hand, this document discloses pharmaceutical compositions comprising ASD, wherein the ASD comprises an API. In some embodiments, the API is a free base of lurasidone or a pharmaceutically acceptable salt thereof. In some embodiments, the API is lurasidone hydrochloride.

[0279] In some embodiments, ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof (such as lurasidone hydrochloride), wherein the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 3% to about 60% by weight of ASD. In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 10% to about 50%. In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 15% to about 30%. In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at a weight percentage of from about 25% to about 40%. In some embodiments, ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof, wherein the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 3% to about 50% by weight of ASD. In some embodiments, ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof, wherein the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 5% by weight to about 40% by weight of ASD. In some embodiments, ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof, wherein the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 10% by weight to about 35% by weight of ASD.

[0280] In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof (such as lurasidone hydrochloride) is present in the amorphous solid dispersion at a weight percentage of about 5% to about 60%. In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof is present at a weight percentage of about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 5% to about 35%, about 5% to about 40%, about 5% to about 45%, about 5% to about 50%, about 5% to about 55%, about 5% to about 60%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%. %, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% The amorphous solids dispersion is present in the amorphous solids dispersion at weight percentages of about 60%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 50% to about 55%, about 50% to about 60%, or about 55% to about 60%. In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof is present in the amorphous solids dispersion at weight percentages of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion at a weight percentage of at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or about 55%.In some embodiments, the free base of lurasidone or a pharmaceutically acceptable salt thereof is present in the amorphous solid dispersion in weight percentages of up to about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%.

[0281] In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is nonionic. In some embodiments, the hydrophilic polymer is ionic. In some embodiments, the hydrophilic polymer is an enteric polymer. In some embodiments, the pharmaceutical composition described herein comprises ASD, wherein the ASD comprises a hydrophilic polymer. In some embodiments, the hydrophilic polymer is HPMC. In some embodiments, the hydrophilic polymer is polymethacrylate. In some embodiments, the hydrophilic polymer is PVP / VA. In some embodiments, the hydrophilic polymer is HPMC AS. In some embodiments, the hydrophilic polymer is PVP. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof. In some embodiments, the hydrophilic polymer is present in an amount from about 1% by weight to about 80% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount from about 5% by weight to about 70% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount from about 10% by weight to about 60% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount from about 20% by weight to about 50% by weight of ASD. In some embodiments, the hydrophilic polymer is present in an amount of about 20% to about 40% by weight of ASD.

[0282] In some embodiments, ASD comprises a surfactant. In some embodiments, ASD optionally comprises a surfactant. In some embodiments, the surfactant is TPGS. In some embodiments, the surfactant is PEG. In some embodiments, the surfactant is a block copolymer of polyethylene glycol and polypropylene glycol. In some embodiments, the surfactant is polyoxyethylene hydrogenated castor oil. In some embodiments, the surfactant is lecithin. In some embodiments, the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof. In some embodiments, the surfactant comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol ester, polysorbate, or a combination thereof. In some embodiments, the surfactant comprises lecithin and TPGS. In some embodiments, the surfactant comprises lecithin. In some embodiments, the surfactant comprises PEG. In some embodiments, the surfactant comprises a block copolymer of polyethylene glycol and polypropylene glycol. In some embodiments, the surfactant comprises SLS. In some embodiments, the surfactant comprises a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam. In some embodiments, the surfactant comprises polyoxyethylene hydrogenated castor (e.g., sold under the trade name RH40). In some embodiments, the surfactant comprises polysorbate. In some embodiments, the surfactant comprises polyoxyethylene glycerol (e.g., Labrasol or Gelucire). In some embodiments, the surfactant comprises TPGS. In some embodiments, the surfactant is present in an amount of about 5% to about 60% by weight of ASD. In some embodiments, the surfactant is present in an amount of about 5% to about 40% by weight of ASD. In some embodiments, the surfactant is present in an amount of about 5% to about 30% by weight of ASD.

[0283] In some embodiments, ASD comprises an inorganic acid or an organic acid. In some embodiments, ASD optionally comprises an organic acid. In some embodiments, ASD comprises an organic acid, wherein the organic acid is tartaric acid or citric acid or a combination thereof. In some embodiments, the organic acid is tartaric acid. In some embodiments, the organic acid is citric acid. In some embodiments, the organic acid is citric acid. In some embodiments, the inorganic acid or organic acid is present in an amount of about 10% by weight to about 40% by weight of ASD. In some embodiments, the organic acid is citric acid. In some embodiments, the inorganic acid or organic acid is present in an amount of about 10% by weight to about 30% by weight of ASD.

[0284] In some embodiments, ASD optionally includes an adsorbent. In some embodiments, the adsorbent is silica. In some embodiments, the adsorbent is present in an amount of about 15% by weight to about 40% by weight of ASD.

[0285] In some embodiments, the ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof (such as lurasidone hydrochloride). In some embodiments, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 5% to about 50% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 10% to about 70% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 10% to about 40% by weight of the ASD. In some embodiments, the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 10% to about 40% by weight of the ASD. In some embodiments, the organic acid is tartaric acid or citric acid, or a combination thereof, and optionally an adsorbent. In some embodiments, the amount of adsorbent is from about 15% to about 40% by weight of ASD. In some embodiments, the adsorbent is SiO2.

[0286] In some embodiments, ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof (such as lurasidone hydrochloride). In some embodiments, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 15% to about 40% by weight of ASD. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 15% to about 60% by weight of ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 10% to about 30% by weight of ASD. In some embodiments, the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 15% to about 40% by weight of ASD. In some embodiments, the organic acid is tartaric acid or citric acid, or a combination thereof. In some embodiments, ASD comprises an adsorbent. In some embodiments, the amount of adsorbent is about 15% to about 30% by weight of ASD. In some embodiments, the adsorbent is SiO2.

[0287] In some embodiments, the pharmaceutical compositions described herein comprise ASD, which comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is about 25% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is about 25% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is about 25% by weight of the ASD. In some embodiments, the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is about 25% by weight of the ASD. In some embodiments, the organic acid is tartaric acid.

[0288] In some embodiments, the pharmaceutical compositions described herein comprise ASD, which comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is about 25% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is about 25% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of the surfactant is about 25% by weight of the ASD. In some embodiments, the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the amount of the organic acid is about 25% by weight of the ASD. In some embodiments, the organic acid is citric acid.

[0289] In some embodiments, the pharmaceutical composition described herein comprises ASD, which comprises a free lumasidon base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of the free lumasidon base or a pharmaceutically acceptable salt thereof is from about 5% to 50% by weight of the ASD. In some embodiments, the amount of the free lumasidon base or a pharmaceutically acceptable salt thereof is from about 10% to 30% by weight of the ASD. In some embodiments, the amount of the free lumasidon base or a pharmaceutically acceptable salt thereof is from about 10 to 25% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 5% to about 70% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 15% to about 65% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 15% to about 40% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is from about 13% by weight of the ASD. In some embodiments, the hydrophilic polymer is VA64, HPMC-E5, HPMCAS-LF, PVP-K30, or any combination thereof. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the hydrophilic polymer is HPMC-E5. In some embodiments, the hydrophilic polymer is PVP-K30. In some embodiments, the hydrophilic polymer is HPMC-LF. In some embodiments, the hydrophilic polymer comprises HPMC, HPMC, a graft copolymer based on polyvinyl acetate and polyvinylcaprolactam, PVP, copovidone, polymethacrylate, or a combination thereof. In some embodiments, the ASD comprises a surfactant. In some embodiments, the amount of surfactant is from about 10% by weight to about 50% by weight of the ASD. In some embodiments, the amount of surfactant is from about 9% by weight to about 40% by weight of the ASD. In some embodiments, the amount of surfactant is from about 15% by weight to about 30% by weight of the ASD. In some embodiments, the amount of surfactant is from about 20% by weight to about 25% by weight of the ASD. In some embodiments, the surfactant is TPGS. In some embodiments, the amount of TPGS is from about 9-30% by weight of the ASD. In some embodiments, the surfactant is lecithin. In some embodiments, lecithin is present in an amount of about 9-25% by weight of the ASD. In some embodiments, the surfactant is RH40. In some embodiments, RH40 is present in an amount of about 18% by weight of ASD. In some embodiments, the surfactant is Pluronic F-68. In some embodiments, Pluronic F-68 is present in an amount of about 18% by weight of ASD. In some embodiments, the surfactant is PEG6000. In some embodiments, PEG6000 is present in an amount of about 18% by weight of ASD.In some embodiments, the surfactant comprises phospholipids or derivatives thereof, such as lecithin, polyethylene glycol (PEG), block copolymers of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, graft copolymers based on polyvinyl acetate and polyvinylcaprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerol esters, polysorbate esters, or combinations thereof. In some embodiments, the ASD comprises an organic acid. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 40% by weight of the ASD. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 35% by weight of the ASD. In some embodiments, the organic acid is present in an amount of about 10% by weight to about 30% by weight of the ASD. In some embodiments, the organic acid is tartaric acid. In some embodiments, tartaric acid is present in an amount of about 10% by weight to about 35% by weight of the ASD. In some embodiments, the organic acid is citric acid. In some embodiments, citric acid is present in an amount of about 10% by weight to 25% by weight of the ASD. In some embodiments, the ASD comprises an adsorbent. In some embodiments, the adsorbent is present in an amount of about 15% to about 40% by weight of ASD. In some embodiments, the adsorbent is present in an amount of about 10% to about 30% by weight of ASD. In some embodiments, the adsorbent is SiO2.

[0290] In some embodiments, the pharmaceutical composition described herein comprises an ASD comprising: a lumasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of the lumasidone free base or a pharmaceutically acceptable salt thereof is from about 10% to 30% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 25% to 60% by weight of the ASD, and wherein the hydrophilic polymer is HPMCAS-LF; and a surfactant, wherein the surfactant is from about 9% to about 25% by weight of the ASD, wherein the surfactant is TPGS, lecithin, or any combination thereof.

[0291] In some embodiments, the pharmaceutical composition described herein comprises an ASD consisting of: a lumasidon free base or a pharmaceutically acceptable salt thereof, wherein the amount of the lumasidon free base or a pharmaceutically acceptable salt thereof is from about 13% to about 30% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 25% to about 65% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5, VA64, PVP-K30 or HPMC-E5; a surfactant, wherein the surfactant is TPGS; and an organic acid, wherein the organic acid is present in an amount from about 13% to 29% by weight of the ASD, and wherein the organic acid is tartaric acid or citric acid.

[0292] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: a lumasidon free base or a pharmaceutically acceptable salt thereof, wherein the amount of the lumasidon free base or a pharmaceutically acceptable salt thereof is from about 13% to 22% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 22% to 46% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS-LF or HPMC-E5; a surfactant, wherein the amount of the surfactant is from about 13% to 22% by weight of the ASD, wherein the surfactant is TPGS, lecithin, or any combination thereof; and an absorbent, wherein the amount of the absorbent is from about 20-33% by weight of the ASD, wherein the absorbent is SiO2.

[0293] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: a lumasidon free base or a pharmaceutically acceptable salt thereof, wherein the amount of the lumasidon free base or a pharmaceutically acceptable salt thereof is about 11% to 20% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is about 11-30% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5; a surfactant, wherein the amount of the surfactant is about 11% to 20% by weight of the ASD, wherein the surfactant is TPGS, RH40, Pluronic F-68, PEG6000 or lecithin or any combination thereof; an organic acid, wherein the amount of the organic acid is about 11-20% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid; and an adsorbent, wherein the amount of the adsorbent is about 10% to 27% by weight of the ASD, wherein the adsorbent is SiO2.

[0294] In some embodiments, the pharmaceutical compositions described herein comprise ASD, said ASD comprising lurasidone free base or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is about 10-30% by weight of the ASD. In some embodiments, the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is about 15-20% by weight of the ASD. In some embodiments, the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is about 15% by weight of the ASD. In some embodiments, the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is about 18% by weight of the ASD. In some embodiments, the ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is about 10% by weight to about 30% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 10% by weight to about 20% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 15% by weight of the ASD. In some embodiments, the amount of the hydrophilic polymer is about 18% by weight of the ASD. In some embodiments, the hydrophilic polymer is HPMC-E5, HPMCAS, PVP, or PVP / VA or a combination thereof. In some embodiments, the hydrophilic polymer is HPMC-E5. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the hydrophilic polymer is VA64. In some embodiments, the ASD contains a surfactant. In some embodiments, the amount of surfactant is from about 10% by weight to about 40% by weight of the ASD. In some embodiments, the amount of surfactant is from about 10% by weight to about 20% by weight of the ASD. In some embodiments, the amount of surfactant is from about 18% by weight of the ASD. In some embodiments, the amount of surfactant is from about 20% by weight to about 40% by weight of the ASD. In some embodiments, the amount of surfactant is from about 31% by weight of the ASD. In some embodiments, the surfactant is TPGS or lecithin or a combination thereof. In some embodiments, TPGS is present in an amount of about 15% by weight of the ASD. In some embodiments, lecithin is present in an amount of about 15% by weight of the ASD. In some embodiments, the ASD contains an organic acid. In some embodiments, the organic acid is present in an amount of from about 10% by weight to about 30% by weight of the ASD. In some embodiments, the organic acid is present in an amount of about 10% to about 20% by weight of the ASD. In some embodiments, the organic acid is present in an amount of about 15% by weight of the ASD. In some embodiments, the organic acid is present in an amount of about 18% by weight of the ASD. In some embodiments, the organic acid is citric acid or tartaric acid or a combination thereof. In some embodiments, the organic acid is citric acid. In some embodiments, the organic acid is tartaric acid. In some embodiments, the ASD contains an adsorbent. In some embodiments, the adsorbent is present in an amount of about 15% to about 40% by weight of the ASD.In some embodiments, the adsorbent is present in an amount of about 20% to about 30% by weight of ASD. In some embodiments, the adsorbent is present in an amount of about 23% by weight of ASD. In some embodiments, the adsorbent is present in an amount of about 27% by weight of ASD. In some embodiments, the adsorbent is SiO2.

[0295] In some embodiments, the pharmaceutical composition described herein comprises ASD, the ASD comprising: a free base of lurasidone or a pharmaceutically acceptable salt thereof, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof being about 15% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being about 15% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5; TPGS, the amount of the TPGS being about 15% by weight of the ASD; lecithin, the amount of the lecithin being about 15% by weight of the ASD; citric acid, the amount of the citric acid being about 15% by weight of the ASD; and an adsorbent, the amount of the adsorbent being about 23% by weight of the ASD, wherein the adsorbent is SiO2.

[0296] In some embodiments, the pharmaceutical composition described herein comprises ASD, the ASD comprising: a free base of lurasidone or a pharmaceutically acceptable salt thereof, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof being about 18% by weight of the ASD; a hydrophilic polymer, the amount of the hydrophilic polymer being about 18% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5; TPGS, the amount of the TPGS being about 18% by weight of the ASD; citric acid, the amount of the citric acid being about 18% by weight of the ASD; and an adsorbent, the amount of the adsorbent being about 27% by weight of the ASD, wherein the adsorbent is SiO2.

[0297] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: a lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of the lurasidone free base or a pharmaceutically acceptable salt thereof is from about 10% to about 30% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is from about 10% to about 30% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5, HPMCAS, PVP, or PVP / VA or a combination thereof; a surfactant, wherein the amount of the surfactant is from about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, lecithin, or a combination thereof; an organic acid, wherein the amount of the organic acid is from about 10% to about 30% by weight of the ASD, wherein the organic acid is citric acid; and optionally an adsorbent, wherein the amount of the adsorbent is from about 15% to about 40% by weight of the ASD, wherein the adsorbent is SiO2.

[0298] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: lurasidone free base or a pharmaceutically acceptable salt thereof, the amount of which is about 15% by weight of ASD; a hydrophilic polymer, the amount of which is about 15% by weight of ASD, wherein the hydrophilic polymer is HPMC-E5; TPGS, the amount of which is about 15% by weight of ASD; lecithin, the amount of which is about 15% by weight of ASD; citric acid, the amount of which is about 15% by weight of ASD; and an adsorbent, the amount of which is about 23% by weight of ASD, wherein the adsorbent is SiO2.

[0299] In some embodiments, the pharmaceutical composition described herein comprises ASD, which consists of: a lumasidon free base or a pharmaceutically acceptable salt thereof, wherein the amount of the lumasidon free base or a pharmaceutically acceptable salt thereof is about 18% by weight of the ASD; a hydrophilic polymer, wherein the amount of the hydrophilic polymer is about 18% by weight of the ASD, wherein the hydrophilic polymer is HPMC-E5; TPGS, wherein the amount of the TPGS is about 18% by weight of the ASD; citric acid, wherein the amount of the citric acid is about 18% by weight of the ASD; and an adsorbent, wherein the amount of the adsorbent is about 27% by weight of the ASD, wherein the adsorbent is SiO2.

[0300] In some embodiments, ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 20 mg to about 80 mg. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 20 mg to about 180 mg. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 20 mg to about 70 mg. In some embodiments, the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 20 mg to about 70 mg. In some embodiments, the organic acid is tartaric acid or citric acid, or a combination thereof. In some embodiments, ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 30 mg to about 100 mg. In some embodiments, the adsorbent is SiO2. In some embodiments, the pharmaceutical compositions comprising ASD described herein are dispensed in unit dosage forms.

[0301] In some embodiments, ASD comprises a free base of lurasidone or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of the free base of lurasidone or a pharmaceutically acceptable salt thereof is from about 20 mg to about 60 mg. In some embodiments, ASD comprises a hydrophilic polymer. In some embodiments, the amount of the hydrophilic polymer is from about 20 mg to about 160 mg. In some embodiments, the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof. In some embodiments, ASD comprises a surfactant. In some embodiments, the amount of the surfactant is from about 20 mg to about 60 mg. In some embodiments, the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof. In some embodiments, ASD comprises an organic acid. In some embodiments, the amount of the organic acid is from about 20 mg to 60 mg. In some embodiments, the organic acid is tartaric acid or citric acid, or a combination thereof. In some embodiments, ASD comprises an adsorbent. In some embodiments, the amount of the adsorbent is from about 30 mg to about 80 mg. In some embodiments, the adsorbent is SiO2. In some embodiments, the pharmaceutical compositions comprising ASD described herein are dispensed in unit dosage forms.

[0302] In some embodiments, the pharmaceutical compositions comprising an ASD described herein have acceptable storage stability, wherein the ASD comprises a free lurasidone base or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical compositions are chemically stable at 75°C / 75% RH for at least 2 weeks, wherein the degradation of the API in the storage-stable pharmaceutical compositions is less than 5% at the end of the storage period. In some embodiments, the pharmaceutical compositions are stable at 40°C / 75% RH for at least 6 months, wherein the storage-stable pharmaceutical compositions have less than 0.5% of any impurities at the end of the storage period. In some embodiments, the pharmaceutical compositions are stable at 25°C / 60% RH for at least 2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months, or 24 months, wherein the storage-stable pharmaceutical compositions have less than 0.5% of any impurities at the end of the storage period.

[0303] In some embodiments, when administered orally, the AUC, AUC inf or AUC last When measured, the bioavailability of the pharmaceutical composition described herein is superior to that of the corresponding reference composition containing lurasidone hydrochloride. In some embodiments, when measured after oral administration, the bioavailability is measured in AUC, AUCinf, or AUC. lastWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing lumrasidone hydrochloride. In some embodiments, when administered orally, C max When measured, the bioavailability of the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of the corresponding compositions containing crystalline rurasidone hydrochloride.

[0304] In some embodiments, when administered orally, the AUC, AUC inf or AUC last When measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of LATUDA capsules containing lurasidone hydrochloride. In some embodiments, when administered orally, C maxWhen measured, the bioavailability exhibited by the pharmaceutical compositions described herein is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, or 10 times that of LATUDA capsules containing lurasidone hydrochloride. In some embodiments, the bioavailability exhibited by the pharmaceutical compositions is about 1.1 to about 10 times higher than that of LATUDA. In some embodiments, the bioavailability of the pharmaceutical composition is about 1.1 times to about 3 times, about 1.1 times to about 5 times, about 1.1 times to about 6 times, about 1.1 times to about 7 times, about 1.1 times to about 8 times, about 1.1 times to about 10 times, about 1.5 times to about 2 times, about 1.5 times to about 3 times, about 1.5 times to about 4 times, about 1.5 times to about 5 times, about 1.5 times to about 6 times, about 1.5 times to about 7 times, about 1.5 times to about 8 times, about 1.5 times to about 10 times, about 2 times to about 4 times, about 2 times to about 5 times, about 2 times to about 6 times, about 2 times to about 7 times, about 2 times to about 8 times, about 2 times to about 10 times, or about 5 times to about 10 times. In some embodiments, the pharmaceutical composition comprises an ASD, said ASD comprising lurasidone or lurasidone hydrochloride. In some embodiments, bioavailability is measured under fasting conditions.

[0305] In some embodiments, when administered orally at AUC last Or C max When measured, the pharmaceutical compositions described herein exhibit bioavailability that is at least about 1.1 times, about 1.3 times, about 1.5 times, about 1.8 times, about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, or about 8 times higher than the bioavailability of LATUDA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 2 times higher than the bioavailability of LATUDA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at least about 4 times higher than the bioavailability of LATUDA. In some embodiments, the pharmaceutical compositions exhibit bioavailability that is at most about 1.3...

Claims

1. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), wherein the ASD comprises: a) an active pharmaceutical ingredient (API), the API being present in an amount of about 5% to about 60% by weight of the ASD, wherein the API is cabozantinib or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an acid; and e) optionally an adsorbent.

2. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), wherein the ASD comprises: a) an active pharmaceutical ingredient (API) in an amount of about 5 wt % to about 35 wt % of the ASD, wherein the API is cabozantinib or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, a polyvinyl caprolactam-based graft copolymer (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; and d) optionally an adsorbent in an amount of about 1 wt % to 40 wt % of the ASD, wherein the adsorbent is silica.

3. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), wherein the ASD comprises: a) an active pharmaceutical ingredient (API), the API being present in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the API is venetoclax or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5 wt % to about 50 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an acid; and e) optionally an adsorbent.

4. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5 wt % to about 45 wt % of the ASD, wherein the API is venetoclax or a pharmaceutically acceptable salt thereof; b) a surfactant in an amount of about 5 wt % to about 50 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, a polyvinyl caprolactam-based graft copolymer (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, or a combination thereof; c) a nonionic hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an inorganic or organic acid in an amount of about 1% to 20% by weight of the ASD; and e) optionally an adsorbent in an amount of about 1 wt % to 40 wt % of the ASD, wherein the adsorbent is silica.

5. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API), the API being present in an amount of about 5% to about 60% by weight of the ASD, wherein the API is abiraterone or abiraterone acetate; b) optionally, a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an acid; and e) optionally an adsorbent.

6. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API), the API being present in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the API is alectinib or a pharmaceutically acceptable salt thereof; b) optionally, a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an acid; and e) optionally an adsorbent.

7. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API), the API being present in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the API is pazopanib or a pharmaceutically acceptable salt thereof; b) optionally, a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an acid; and e) optionally an adsorbent.

8. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API), the API being present in an amount of about 3 wt % to about 60 wt % of the ASD, wherein the API is lurasidone or a pharmaceutically acceptable salt thereof; b) optionally, a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an acid; and e) optionally an adsorbent.

9. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API), the API being present in an amount of about 5% to about 60% by weight of the ASD, wherein the API is vilazodone or a pharmaceutically acceptable salt thereof; b) optionally, a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; d) optionally an acid; and e) optionally an adsorbent.

10. A pharmaceutical composition, wherein the pharmaceutical composition comprises an amorphous solid dispersion (ASD), the ASD comprising: a) an active pharmaceutical ingredient (API) in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the API is selected from the group consisting of abiraterone acetate, alectinib hydrochloride, pazopanib hydrochloride, lurasidone, and vilazodone; b) optionally, a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, a polyvinyl caprolactam-based graft copolymer (PVAc-PVCap-PEG), polyoxyethylene hydrogenated castor oil, or a combination thereof; c) a hydrophilic polymer in an amount ranging from about 1 wt % to about 90 wt % of the ASD; d) optionally an inorganic or organic acid in an amount of about 5% to 40% by weight of the ASD; and e) optionally, an adsorbent in an amount ranging from about 1 wt % to 40 wt % of the ASD.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the hydrophilic polymer is polyvinyl alcohol (PVA), oligosaccharides, polysaccharides, polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC or hydroxypropyl methylcellulose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, cyclodextrin and its derivatives (CD), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polymethacrylate, polyethylene glycol (PEG), a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PCL-PVAc-PEG) or a combination thereof.

12. A pharmaceutical composition according to any one of claims 1 to 11, wherein the hydrophilic polymer is polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), polymethacrylate, hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinyl pyrrolidone (povidone or PVP), vinyl pyrrolidone-vinyl acetate copolymer (copovidone) or a combination thereof.

13. A pharmaceutical composition according to any one of claims 1 to 11, wherein the hydrophilic polymer comprises polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), polymethacrylate, hydroxypropyl β-cyclodextrin (HP-β-CD), sulfobutyl ether-β-cyclodextrin or a combination thereof.

14. The pharmaceutical composition according to any one of claims 1 to 6, wherein the pharmaceutical composition is in the form of a tablet or a capsule.

15. The pharmaceutical composition according to any one of claims 1 to 7, wherein the API is present in the pharmaceutical composition in an amount of about 5% to 50% by weight.

16. The pharmaceutical composition according to any one of claims 1 to 7, wherein the API is present in the pharmaceutical composition in an amount of about 5% to 30% by weight.

17. The pharmaceutical composition according to any one of claims 1 to 7, wherein the API is present in the pharmaceutical composition in an amount of about 10 mg to about 500 mg.

18. The pharmaceutical composition according to any one of claims 1 to 7, wherein the API is present in the pharmaceutical composition in an amount of about 20 mg to about 200 mg.

19. The pharmaceutical composition according to any one of claims 1 to 7, wherein the API is present in the pharmaceutical composition in an amount of about 40 mg to about 150 mg.

20. The pharmaceutical composition according to any one of claims 1 to 7, wherein the API is present in the pharmaceutical composition in an amount of about 50 mg to about 125 mg.

21. A pharmaceutical composition according to any one of claims 1 to 12, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol, polypropylene glycol, polysorbate, SLS, tocopheryl polyethylene glycol succinate (TPGS), polyethylene glycol castor oil, polyoxyethylene glyceride, sorbitan oleate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG) or any combination thereof.

22. The pharmaceutical composition of any one of claims 1 to 12, wherein the surfactant comprises TPGS.

23. A pharmaceutical composition according to any one of claims 1 to 12, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin.

24. The pharmaceutical composition of any one of claims 1 to 12, wherein the surfactant comprises a block copolymer of polyethylene glycol and polypropylene glycol.

25. The pharmaceutical composition of any one of claims 1 to 12, wherein the surfactant comprises polysorbate, tocopherol polyethylene glycol succinate (TPGS), polyethylene glycol castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, sorbitan oleate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), or a combination thereof.

26. The pharmaceutical composition of any one of claims 1 to 17, wherein the surfactant is present in the pharmaceutical composition in an amount of about 1% to 50% by weight.

27. The pharmaceutical composition of any one of claims 1 to 17, wherein the surfactant is present in the pharmaceutical composition in an amount of about 5% to 30% by weight.

28. The pharmaceutical composition of any one of claims 1 to 17, wherein the surfactant is present in the pharmaceutical composition in an amount of about 10 mg to about 500 mg.

29. The pharmaceutical composition of any one of claims 1 to 17, wherein the surfactant is present in the pharmaceutical composition in an amount of about 20 mg to about 400 mg.

30. The pharmaceutical composition of any one of claims 1 to 17, wherein the surfactant is present in the pharmaceutical composition in an amount of about 40 mg to about 200 mg.

31. The pharmaceutical composition of any one of claims 1 to 22, wherein the hydrophilic polymer is present in the amorphous solid dispersion in an amount of about 1 wt% to about 95 wt%.

32. The pharmaceutical composition of any one of claims 1 to 22, wherein the hydrophilic polymer is present in the amorphous solid dispersion in an amount of about 1 wt% to about 75 wt%.

33. The pharmaceutical composition of any one of claims 1 to 22, wherein the hydrophilic polymer is present in the amorphous solid dispersion in an amount of about 20% to about 60% by weight.

34. The pharmaceutical composition of any one of claims 1 to 22, wherein the hydrophilic polymer is present in the pharmaceutical composition in an amount of about 10 mg to about 500 mg.

35. A pharmaceutical composition according to any one of claims 1 to 25, wherein the adsorbent is selected from silicon dioxide, activated carbon, magnesium aluminum silicate, diatomaceous earth, microcrystalline cellulose (MCC), silicified microcrystalline cellulose (SMCC), talc, crospovidone, sodium carboxymethylcellulose, sodium carboxymethyl starch, and is also selected from sugars or sugar alcohols such as sorbitol, mannitol, lactose, cyclodextrin and maltodextrin.

36. A pharmaceutical composition according to any one of claims 1 to 25, wherein the adsorbent is silicon dioxide.

37. The pharmaceutical composition of any one of claims 1 to 27, wherein the adsorbent is present in the amorphous solid dispersion in an amount of about at least 20% by weight (such as 20-30% or 20% to 50%).

38. The pharmaceutical composition of any one of claims 1 to 27, wherein the adsorbent is present in the pharmaceutical composition in an amount of about 30 mg to about 200 mg.

39. The pharmaceutical composition of any one of claims 1 to 27, wherein the adsorbent is present in the pharmaceutical composition in an amount of about 50 mg to about 100 mg.

40. The pharmaceutical composition of any one of claims 1 to 30, wherein the pharmaceutical composition comprises an inorganic acid or an organic acid.

41. The pharmaceutical composition of claim 31, wherein the organic or inorganic acid is selected from fatty acids, tartaric acid, fumaric acid, succinic acid, citric acid, lactic acid, malic acid, methanesulfonic acid, ethanesulfonic acid, isethionic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, and phosphoric acid.

42. The pharmaceutical composition of claim 31, wherein the pharmaceutical composition comprises an organic acid.

43. The pharmaceutical composition of claim 33, wherein the organic acid is selected from the group consisting of long chain fatty acids (e.g., oleic acid), tartaric acid, succinic acid, citric acid, malic acid, and methanesulfonic acid.

44. The pharmaceutical composition of any one of claims 31 to 34, wherein the organic acid or inorganic acid is present in the amorphous solid dispersion in an amount of about 5% to about 50% by weight.

45. The pharmaceutical composition of any one of claims 31 to 34, wherein the organic acid or inorganic acid is present in the amorphous solid dispersion in an amount of about 20% to about 30% by weight.

46. ​​The pharmaceutical composition of any one of claims 31 to 34, wherein the organic acid or inorganic acid is present in the pharmaceutical composition in an amount of about 10 mg to about 500 mg.

47. The pharmaceutical composition of any one of claims 31 to 34, wherein the organic acid or inorganic acid is present in the pharmaceutical composition in an amount of about 10 mg to about 200 mg.

48. The pharmaceutical composition of any one of claims 31 to 34, wherein the organic acid or inorganic acid is present in the pharmaceutical composition in an amount of about 30 mg to about 100 mg.

49. The pharmaceutical composition according to any one of claims 1 to 39, wherein the D50 value of the amorphous solid dispersion is 1 μm to 1000 μm.

50. The pharmaceutical composition of claim 40, wherein the D50 value is from about 1 μm to about 50 μm.

51. The pharmaceutical composition of claim [0005], wherein the ASD comprises: a) cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is about 10 wt % to about 55 wt % of the ASD; b) a surfactant in an amount of about 10% to about 55% by weight of the ASD, wherein the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene glyceride, polyoxyethylene hydrogenated castor, or a combination thereof; c) a hydrophilic polymer in an amount of about 5 wt % to about 70 wt % of the ASD, wherein the hydrophilic polymer is copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, HPMC, HPMCAS, or a combination thereof; d) optionally an adsorbent in an amount of about 5 wt % to 40 wt % of the ASD, wherein the adsorbent is silica; and e) optionally an organic acid in an amount of about 5% to 40% by weight of the ASD, wherein the organic acid is malic acid.

52. The pharmaceutical composition of claim 42, wherein the ASD comprises: a) cabozantinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of cabozantinib free base or a pharmaceutically acceptable salt thereof is about 12% to about 25% by weight of the ASD; b) a surfactant in an amount ranging from about 15% to about 50% by weight of the ASD, wherein the surfactant comprises lecithin, TPGS, or a combination thereof; c) a hydrophilic polymer in an amount of about 10 wt % to about 50 wt % of the ASD, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), copovidone, polymethacrylate, or a combination thereof; d) optionally an adsorbent in an amount of about 15% to 30% by weight of the ASD, wherein the adsorbent is silica; and e) optionally an organic acid in an amount of about 10% to 30% by weight of the ASD, wherein the organic acid is malic acid.

53. The pharmaceutical composition according to claim [0005], wherein the pharmaceutical composition is formulated in a unit dosage form, the unit dosage form comprising: a) cabozantinib free base or cabozantinib malate in an amount of about 20 mg to about 200 mg; b) a surfactant in an amount of about 20 mg to about 220 mg, wherein the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene glyceride, polyoxyethylene hydrogenated castor, or a combination thereof; c) a hydrophilic polymer in an amount of about 40 mg to about 250 mg, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, HPMCAS or a combination thereof; d) optionally an adsorbent in an amount of about 40 mg to about 200 mg, wherein the adsorbent is silica; and e) optionally an organic acid in an amount of about 20 mg to about 200 mg, wherein the organic acid is malic acid.

54. The pharmaceutical composition of claim 44, wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) cabozantinib free base or cabozantinib malate in an amount of about 20 mg to about 80 mg; b) a surfactant in an amount of about 20 mg to about 200 mg, wherein the surfactant comprises lecithin, TPGS, or a combination thereof; c) a hydrophilic polymer in an amount of about 20 mg to about 150 mg, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), copovidone, polymethacrylate or a combination thereof; d) optionally an adsorbent in an amount of about 30 mg to about 100 mg, wherein the adsorbent is silica; and e) optionally an organic acid in an amount of about 20 mg to about 70 mg, wherein the organic acid is malic acid.

55. An amorphous solid dispersion (ASD), wherein the amorphous solid dispersion comprises: a) cabozantinib free base or cabozantinib malate; b) surfactant; c) hydrophilic polymer; d) optionally an adsorbent; and e) optionally an organic acid.

56. The ASD of claim 46, wherein the ASD comprises: a) cabozantinib free base or cabozantinib malate; b) a surfactant, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate or a combination thereof; c) a hydrophilic polymer, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, HPMCAS or a combination thereof; d) optionally an adsorbent, wherein the adsorbent is silica; and e) optionally an organic acid, wherein the organic acid is malic acid.

57. The ASD of claim 47, wherein the ASD comprises: a) cabozantinib free base or cabozantinib malate, wherein the amount of cabozantinib free base or cabozantinib malate is about 10% to about 55% by weight of the ASD; b) a surfactant in an amount of about 10% to about 55% by weight of the ASD, wherein the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene glycerides (such as caprylocaproyl polyoxyethylene-8 glyceride), polyoxyethylene hydrogenated castor, or a combination thereof; c) a hydrophilic polymer, the amount of the hydrophilic polymer accounting for about 5% to about 70% by weight of the ASD, wherein the non-ionic hydrophilic polymer is HPMC (such as HPMC-E5), copovidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, HPMCAS or a combination thereof; d) optionally an adsorbent in an amount of about 5 wt % to 40 wt % of the ASD, wherein the adsorbent is silica; and e) optionally an organic acid in an amount of about 5% to 40% by weight of the ASD, wherein the organic acid is malic acid.

58. The pharmaceutical composition according to any one of claims 42 to 48, wherein after oral administration under fasting conditions, C max or AUC last When measured, the pharmaceutical composition exhibits a bioavailability that is about 75% to about 200% of the bioavailability of a corresponding reference composition comprising cabozantinib, wherein the reference pharmaceutical composition does not comprise the amorphous solid dispersion.

59. A method of treating a disease or condition, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims 1 to 48.

60. A method of treating cancer, the method comprising administering to a subject in need thereof the pharmaceutical composition or amorphous solid dispersion of any one of claims 1, 2, or 42 to 48.

61. The method of claim 50, wherein the cancer comprises kidney cancer, liver cancer, and thyroid cancer.

62. The method of claim 50, wherein the renal cancer is advanced renal cell carcinoma.

63. The method of claim 50, wherein the liver cancer is hepatocellular carcinoma.

64. The method of claim 50, wherein the thyroid cancer is locally advanced or metastatic differentiated thyroid cancer or medullary thyroid cancer.

65. A method of inhibiting multiple tyrosine kinases, the method comprising administering to a subject in need thereof the pharmaceutical composition or amorphous solid dispersion of any one of claims 1, 2, or 42 to 48.

66. The method of claim 65, wherein the plurality of tyrosine kinases comprises VEGFR2, c-MET, or RET.

67. The method of any one of claims 49 to 66, further comprising administering an immunotherapeutic agent.

68. The method of claim 57, wherein the immunotherapeutic agent is nivolumab.

69. The method of any one of claims 49 to 66, wherein the subject was previously treated with sorafenib.

70. The method according to any one of claims 49 to 66, wherein a) the subject is 12 years old or older, b) the subject has progressed following prior VEGFR-targeted therapy, and c) The subject is refractory or ineligible for radioiodine.

71. The pharmaceutical composition of claim 2, wherein the ASD comprises: a) venetoclax or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax or a pharmaceutically acceptable salt thereof is about 10% to about 50% by weight of the ASD; b) a surfactant in an amount of about 10% to about 50% by weight of the ASD, wherein the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, TPGS, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerides (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount of about 10 wt % to about 50 wt % of the ASD, wherein the hydrophilic polymer is copolyvidone, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), polymethacrylate, HPMCAS, or a combination thereof; d) optionally an organic acid in an amount of about 1% to 20% by weight of the ASD, wherein the organic acid is citric acid; and e) optionally an adsorbent in an amount of about 5 wt % to 40 wt % of the ASD, wherein the adsorbent is silica.

72. The pharmaceutical composition of claim 4 or 61, wherein the ASD comprises: a) venetoclax or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax or a pharmaceutically acceptable salt thereof is about 20% to about 50% by weight of the ASD; b) a surfactant in an amount of about 20% to about 40% by weight of the ASD, wherein the surfactant is TPGS, lecithin, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount of about 20 wt % to about 40 wt % of the ASD, wherein the hydrophilic polymer is copolyvidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), HPMCAS, or a combination thereof; d) optionally an organic acid in an amount of about 3% to 20% by weight of the ASD, wherein the organic acid is citric acid; and e) optionally an adsorbent in an amount of about 10% to 40% by weight of the ASD, wherein the adsorbent is silica.

73. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) venetoclax or a pharmaceutically acceptable salt thereof in an amount of about 60 mg to about 300 mg; b) a surfactant, the amount of the surfactant being from about 20 mg to about 450 mg, wherein the surfactant is TPGS, lecithin, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate or a combination thereof; c) a hydrophilic polymer in an amount of about 50 mg to about 450 mg, wherein the hydrophilic polymer is copolyvidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), HPMCAS or a combination thereof; d) optionally an organic acid in an amount of about 5 mg to about 150 mg, wherein the organic acid is citric acid; and e) optionally an adsorbent in an amount of about 10 mg to about 300 mg, wherein the adsorbent is silica.

74. The pharmaceutical composition of claim 63, wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) venetoclax or a pharmaceutically acceptable salt thereof in an amount of about 80 mg to about 120 mg; b) a surfactant in an amount of about 70 mg to about 130 mg, wherein the surfactant is TPGS, lecithin, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, or a combination thereof; c) a hydrophilic polymer in an amount of about 70 mg to about 130 mg, wherein the hydrophilic polymer is copolyvidone, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), HPMCAS or a combination thereof; d) optionally an organic acid in an amount of about 10 mg to about 40 mg, wherein the organic acid is citric acid; and e) optionally an adsorbent in an amount of about 50 mg to about 180 mg, wherein the adsorbent is silica.

75. An amorphous solid dispersion (ASD), wherein the amorphous solid dispersion comprises: a) venetoclax or a pharmaceutically acceptable salt thereof; b) surfactant; c) hydrophilic polymer; d) optionally an organic acid; and e) optionally an adsorbent.

76. The ASD of claim 65, wherein the ASD comprises: a) venetoclax or a pharmaceutically acceptable salt thereof; b) a surfactant, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate or a combination thereof; c) a hydrophilic polymer, wherein the hydrophilic polymer is copolyvidone, HPMCAS, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG), or a combination thereof; and d) optionally an organic acid, wherein the organic acid is citric acid.

77. The ASD of claim 66, wherein the ASD comprises: a) venetoclax or a pharmaceutically acceptable salt thereof, wherein the amount of venetoclax or a pharmaceutically acceptable salt thereof is about 10% to about 50% by weight of the ASD; b) a surfactant in an amount of about 10% to about 50% by weight of the ASD, wherein the surfactant comprises lecithin, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerides (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, TPGS, or a combination thereof; c) a hydrophilic polymer in an amount of about 10% to about 50% by weight of the ASD, wherein the hydrophilic polymer is copolyvidone (such as VA64), polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam (PVAc-PVCap-PEG); and d) optionally an organic acid in an amount of about 1% to 20% by weight of the ASD, wherein the organic acid is citric acid; and e) optionally an adsorbent in an amount of about 10% to 40% by weight of the ASD, wherein the adsorbent is silica.

78. The pharmaceutical composition according to any one of claims 61 to 67, wherein after oral administration under fasting conditions, C max or AUC last When measured, the pharmaceutical composition exhibits a bioavailability that is about 75% to about 200% of the bioavailability of a corresponding reference composition comprising venetoclax, wherein the reference pharmaceutical composition does not comprise the amorphous solid dispersion.

79. A method of treating a disease or condition, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims 2, 4, or 61 to 78.

80. A method of treating cancer, the method comprising administering to a subject in need thereof the pharmaceutical composition or amorphous solid dispersion of any one of claims 2, 4, or 61 to 78.

81. The method of claim 69, wherein the cancer is a blood cancer.

82. The method of claim 70, wherein the blood cancer is chronic lymphocytic leukemia.

83. The method of claim 70, wherein the blood cancer is acute myeloid leukemia.

84. The method of claim 69, wherein the cancer is a solid tumor.

85. The method of claim 73, wherein the solid tumor is a lymphoma.

86. The method of claim 74, wherein the lymphoma is small lymphocytic lymphoma.

87. A method of inhibiting B-cell lymphoma-2 (Bcl-2) protein, the method comprising administering to a subject in need thereof the pharmaceutical composition or amorphous solid dispersion of any one of claims 2 or 61 to 67.

88. The method of any one of claims 69 to 71 or 73 to 76, further comprising administering an immunotherapeutic agent.

89. The method of claim 77, wherein the immunotherapeutic agent is obinutuzumab or rituximab.

90. The method of any one of claims 69 to 70 or 72, further comprising administering a chemotherapeutic agent.

91. The method of claim 79, wherein the chemotherapeutic agent is azacitidine, or decitabine, or low-dose cytarabine.

92. The method of any one of claims 69 to 78, wherein the subject has not been previously treated.

93. The method of any one of claims 69 to 71 or 73 to 78, wherein the subject has been previously treated.

94. The method of any one of claims 69 to 70, 72 or 79 to 80, wherein a) the subject is newly diagnosed with acute myeloid leukemia; and b) the subject is 75 years of age or older; or c) The subject suffers from other medical conditions that prevent the use of standard chemotherapy.

95. The method of any one of claims 69 to 78, wherein the subject is an adult.

96. The pharmaceutical composition of claim 5, wherein the ASD comprises: a) abiraterone free base or abiraterone acetate, wherein the amount of abiraterone free base or abiraterone acetate is about 5% to about 50% by weight of the ASD; b) a hydrophilic polymer in an amount ranging from about 5% to about 70% by weight of the ASD; c) a surfactant, the surfactant being present in an amount of about 10 wt % to about 50 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 35% by weight of the ASD; and e) an adsorbent in an amount ranging from about 15 wt % to about 40 wt % of the ASD.

97. The pharmaceutical composition of claim 96, wherein the ASD comprises: a) abiraterone free base or abiraterone acetate, wherein the amount of abiraterone free base or abiraterone acetate is about 5% to about 50% by weight of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 40 wt % of the ASD, wherein the hydrophilic polymer comprises HPMC, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, polymethacrylate, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 35% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

98. The pharmaceutical composition of claim 10, wherein the ASD comprises: a) abiraterone free base or abiraterone acetate, wherein the amount of abiraterone free base or abiraterone acetate is about 5% to about 40% by weight of the ASD; b) a hydrophilic polymer in an amount of about 30% to about 90% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone, or a combination thereof; c) optionally a surfactant in an amount ranging from about 10% to about 40% by weight of the ASD, wherein the surfactant is lecithin or TPGS or a combination thereof; d) optionally an organic acid in an amount of about 5% to 30% by weight of the ASD; and e) optionally, an adsorbent in an amount ranging from about 1 wt % to 50 wt % of the ASD.

99. The pharmaceutical composition of claim 98, wherein the ASD comprises: a) abiraterone free base or abiraterone acetate, wherein the amount of abiraterone free base or abiraterone acetate is about 8% to about 30% by weight of the ASD; b) a hydrophilic polymer in an amount of about 50% to about 90% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone (such as VA64), or a combination thereof; c) optionally a surfactant in an amount of about 15% to about 30% by weight of the ASD, wherein the surfactant is lecithin or TPGS or a combination thereof; d) optionally an organic acid in an amount of about 5% to 30% by weight of the ASD, wherein the organic acid is tartaric acid, oleic acid, or a combination thereof; and e) optionally, an adsorbent in an amount of about 1 wt % to 40 wt % of the ASD, wherein the adsorbent is silica or magnesium aluminum silicate or a combination thereof.

100. The pharmaceutical composition of claim 3, wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) abiraterone free base or abiraterone acetate in an amount of about 20 mg to about 250 mg; b) a hydrophilic polymer in an amount of about 80 mg to about 700 mg, wherein the hydrophilic polymer is HPMCAS, polymethacrylate or copovidone or a combination thereof; c) optionally a surfactant in an amount of about 10 mg to about 250 mg, wherein the surfactant is lecithin or TPGS or a combination thereof; d) optionally an organic acid in an amount of about 10 mg to about 250 mg; and e) optionally an adsorbent in an amount of about 10 mg to about 400 mg.

101. The pharmaceutical composition of claim 87, wherein the ASD comprises: a) abiraterone free base or abiraterone acetate in an amount of about 30 mg to about 120 mg; b) a hydrophilic polymer in an amount of about 100 mg to about 600 mg, wherein the hydrophilic polymer is HPMCAS, polymethacrylate or copovidone (such as VA64) or a combination thereof; c) optionally a surfactant in an amount of about 20 mg to about 150 mg, wherein the surfactant is lecithin or TPGS or a combination thereof; d) optionally an organic acid in an amount of about 10 mg to about 150 mg, wherein the organic acid is tartaric acid, oleic acid, or a combination thereof; and e) optionally an adsorbent in an amount of about 20 mg to about 180 mg, wherein the adsorbent is silicon dioxide or magnesium aluminum silicate or a combination thereof.

102. An amorphous solid dispersion (ASD), wherein the amorphous solid dispersion comprises: a) Abiraterone free base or abiraterone acetate; b) hydrophilic polymer; c) optionally a surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

103. The ASD of claim 89, wherein the ASD comprises: a) Abiraterone free base or abiraterone acetate; b) a hydrophilic polymer, wherein the hydrophilic polymer is HPMCAS, polymethacrylate or copovidone or a combination thereof; c) optionally a surfactant, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerides (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, or a combination thereof; d) optionally an organic acid, wherein the organic acid is tartaric acid, oleic acid, or a combination thereof; and e) optionally an adsorbent, wherein the adsorbent is silicon dioxide or magnesium aluminum silicate or a combination thereof.

104. The ASD of claim 90, wherein the ASD comprises: a) abiraterone free base or abiraterone acetate, wherein the amount of abiraterone free base or abiraterone acetate is about 5% to about 40% by weight of the ASD; b) a hydrophilic polymer in an amount of about 30% to about 80% by weight of the ASD, wherein the hydrophilic polymer is HPMCAS, polymethacrylate, or copovidone (such as VA64), or a combination thereof; c) optionally a surfactant in an amount ranging from about 10% to about 40% by weight of the ASD, wherein the surfactant is lecithin or TPGS or a combination thereof; d) optionally an organic acid in an amount of about 5% to 30% by weight of the ASD, wherein the organic acid is tartaric acid, oleic acid, or a combination thereof; and e) optionally, an adsorbent in an amount of about 1 wt % to 40 wt % of the ASD, wherein the adsorbent is silica or magnesium aluminum silicate or a combination thereof.

105. according to the pharmaceutical composition described in any one of claims 85 to 91, wherein when after oral administration, the AUC last When measured, the pharmaceutical composition exhibits a bioavailability that is about 75% to about 200% of the bioavailability of a corresponding reference composition comprising abiraterone acetate, wherein the reference pharmaceutical composition does not comprise the amorphous solid dispersion, and wherein the dose of the reference formulation is at least 3 times the dose of the pharmaceutical composition.

106. according to the pharmaceutical composition described in any one of claims 85 to 91, wherein when after oral administration with C max When measured, the pharmaceutical composition exhibits a bioavailability that is about 100% to 200% of the bioavailability of a corresponding reference composition comprising abiraterone acetate, wherein the reference pharmaceutical composition does not comprise an amorphous solid dispersion, and wherein the dose of the reference composition is at least 3 times the dose of the pharmaceutical composition.

107. A method of treating a disease or condition, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims 3, 10, or 85 to 93.

108. A method of treating cancer, comprising administering to a subject in need thereof the pharmaceutical composition or amorphous solid dispersion of any one of claims 3, 10, or 85 to 91.

109. The method of claim 95, wherein the cancer is a solid tumor.

110. The method of claim 96, wherein the solid tumor is prostate cancer.

111. The method of claim 97, wherein the prostate cancer is metastatic castration-resistant prostate cancer.

112. The method of claim 97, wherein the prostate cancer is metastatic high-risk castration-sensitive prostate cancer.

113. A method of inhibiting 17α-hydroxylase / C17,20-lyase (CYP17), the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims 3, 10, or 85 to 93.

114. The method of any one of claims 94-98 or 100, further comprising administering a corticosteroid.

115. The method of claim 101, wherein the corticosteroid is prednisone or methylprednisolone.

116. The method of any one of claims 94-97 or 99-100, further comprising administering a corticosteroid.

117. The method of claim 103, wherein the corticosteroid is methylprednisolone.

118. The method of any one of claims 94 to 104, wherein the subject is a male adult.

119. The pharmaceutical composition of claim [0010], wherein the ASD comprises: a) alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of alectinib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 50 wt % of the ASD; b) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; c) a surfactant in an amount of about 10 wt % to about 40 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 35% by weight of the ASD; and e) an adsorbent in an amount ranging from about 15 wt % to about 40 wt % of the ASD.

120. The pharmaceutical composition of claim 119, wherein the ASD comprises: a) alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of alectinib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 50 wt % of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 40 wt % of the ASD, wherein the hydrophilic polymer comprises HPMC, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, polymethacrylate, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 35% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

121. The pharmaceutical composition of claim [0010], wherein the ASD comprises: a) alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of alectinib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 60 wt % of the ASD; b) a hydrophilic polymer in an amount of about 15 wt % to about 80 wt % of the ASD, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, HPMCAS (such as HPMCAS-LF) or PCL-PVAc-PEG (or Soluplus) or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, polyoxyethylene glycerides, polysorbates, polyoxyethylene hydrogenated castor oil, or SLS, or a combination thereof; d) optionally an organic acid in an amount of about 10% to about 50% by weight of the ASD, wherein the organic acid is tartaric acid, citric acid, or malic acid, or a combination thereof; e) optionally an adsorbent in an amount of about 1 wt % to 40 wt % of the ASD, wherein the adsorbent is silica.

122. The pharmaceutical composition of claim 121, wherein the ASD comprises: a) alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of alectinib free base or a pharmaceutically acceptable salt thereof is about 15% to about 55% by weight of the ASD; b) a hydrophilic polymer in an amount of about 15 wt % to about 70 wt % of the ASD, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, HPMCAS or Soluplus or a combination thereof; c) a surfactant in an amount of about 15% to about 30% by weight of the ASD, wherein the surfactant is TPGS, polyoxyethylene glycerides, polysorbates, polyoxyethylene hydrogenated castor oil, or SLS, or a combination thereof; d) optionally an organic acid in an amount of about 20% to about 40% by weight of the ASD, wherein the organic acid is tartaric acid, citric acid, or malic acid, or a combination thereof; and e) optionally an adsorbent in an amount of about 1 wt % to 30 wt % of the ASD, wherein the adsorbent is silica.

123. The pharmaceutical composition of claim [0010], wherein the pharmaceutical composition is formulated in a unit dosage form, the unit dosage form comprising: a) alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of alectinib free base or a pharmaceutically acceptable salt thereof is about 50 mg to about 400 mg; b) a hydrophilic polymer in an amount of about 100 mg to about 1000 mg, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, HPMCAS or Soluplus or a combination thereof; c) a surfactant in an amount of about 40 mg to about 250 mg, wherein the surfactant is TPGS, polyoxyethylene glyceride, polysorbate, polyoxyethylene hydrogenated castor oil or SLS or a combination thereof; d) optionally an organic acid in an amount of about 70 mg to 250 mg, wherein the organic acid is tartaric acid, citric acid or malic acid or a combination thereof; and e) optionally an adsorbent in an amount of about 20 mg to 300 mg, based on the weight of the ASD, wherein the adsorbent is silica.

124. The pharmaceutical composition of claim 108, wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of alectinib free base or a pharmaceutically acceptable salt thereof is about 60 mg to about 180 mg; b) a hydrophilic polymer, the amount of the hydrophilic polymer is about 100 mg to about 900 mg, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, HPMCAS (such as HPMCAS-LF) or Soluplus or a combination thereof; c) a surfactant in an amount of about 50 mg to about 200 mg, wherein the surfactant is TPGS, polyoxyethylene glyceride, polysorbate, polyoxyethylene hydrogenated castor oil or SLS or a combination thereof; d) optionally an organic acid in an amount of about 130 mg to 180 mg, wherein the organic acid is tartaric acid, citric acid or malic acid or a combination thereof; and e) optionally an adsorbent in an amount of about 50 mg to 200 mg, based on the weight of the ASD, wherein the adsorbent is silica.

125. An amorphous solid dispersion (ASD), wherein the amorphous solid dispersion comprises: a) alectinib free base or a pharmaceutically acceptable salt thereof; b) hydrophilic polymer; c) surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

126. The ASD of claim 125, wherein the ASD comprises: a) alectinib free base or a pharmaceutically acceptable salt thereof; b) a hydrophilic polymer, wherein the hydrophilic polymer is HPMC, polymethacrylate, HPMCAS or Soluplus or a combination thereof; c) a surfactant, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (such as caprylocaproyl polyoxyethylene-8 glyceride), polysorbate or a combination thereof; d) optionally an organic acid, wherein the organic acid is tartaric acid, citric acid or malic acid or a combination thereof; and e) optionally an adsorbent, wherein the adsorbent is silica.

127. The ASD of claim 126, wherein the ASD comprises: a) alectinib free base or a pharmaceutically acceptable salt thereof, wherein the amount of alectinib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 60 wt % of the ASD; b) a hydrophilic polymer in an amount of about 15 wt % to about 80 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, HPMCAS or Soluplus or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, polyoxyethylene glycerides, polysorbates, polyoxyethylene hydrogenated castor oil, or SLS, or a combination thereof; d) optionally an organic acid in an amount of about 10% to 50% by weight of the ASD, wherein the organic acid is tartaric acid, citric acid, or malic acid, or a combination thereof; and e) optionally an adsorbent in an amount of about 1 wt % to 40 wt % of the ASD, wherein the adsorbent is silica.

128. according to the pharmaceutical composition described in any one of claims 106 to 112, wherein when after oral administration, the AUC last When measured, the pharmaceutical composition exhibits a bioavailability that is about 75% to about 200% of the bioavailability of a corresponding reference formulation comprising alectinib hydrochloride, wherein the reference pharmaceutical composition does not comprise an amorphous solid dispersion, and wherein the dose of the reference formulation is at least 1.75 times the dose of the pharmaceutical composition.

129. according to the pharmaceutical composition described in any one of claims 106 to 112, wherein when after oral administration with C max When measured, the pharmaceutical composition exhibits a bioavailability that is about 75% to about 200% of the bioavailability of a corresponding reference formulation comprising alectinib hydrochloride, wherein the reference pharmaceutical composition does not comprise an amorphous solid dispersion, and wherein the dose of the reference formulation is at least 1.75 times the dose of the pharmaceutical composition.

130. A method of treating a disease or condition, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0010], 10, or 106 to 129.

131. A method for treating cancer, the method comprising administering to a subject in need thereof the pharmaceutical composition or amorphous solid dispersion of any one of claims [0010], 10, or 106 to 129.

132. The method of claim 131, wherein the cancer is a solid tumor.

133. The method of claim 132, wherein the solid tumor is lung cancer.

134. The method of claim 133, wherein the lung cancer is non-small cell lung cancer.

135. The method of claim 134, wherein the non-small cell lung cancer is anaplastic lymphoma kinase (ALK) positive.

136. A method for inhibiting ALK and / or RET tyrosine kinases, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0010], 10, or 106 to 129.

137. The method of any one of claims 115 to 121, wherein the subject is an adult.

138. The method of any one of claims 115 to 122, wherein the subject is intolerant to crizotinib.

139. The pharmaceutical composition of claim [0012], wherein the ASD comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 40 wt % of the ASD; b) a hydrophilic polymer in an amount of about 1 wt % to about 80 wt % of the ASD, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, HPMCAS, copovidone, or a combination thereof; c) a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant is TPGS or lecithin or a combination thereof; d) optionally an organic acid in an amount from about 10% to about 40% by weight of the ASD, wherein the organic acid is tartaric acid; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

140. The pharmaceutical composition of claim 124, wherein the ASD comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 15% to about 30% by weight of the ASD; b) a hydrophilic polymer in an amount of about 15% to about 60% by weight of the ASD, wherein the hydrophilic polymer is HPMC, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, or a combination thereof; c) a surfactant in an amount of about 15% to about 50% by weight of the ASD, wherein the surfactant is TPGS or lecithin or a combination thereof; d) optionally an organic acid in an amount from about 15% to about 30% by weight of the ASD, wherein the organic acid is tartaric acid; and e) optionally, an adsorbent in an amount of about 20 wt % to about 35 wt % of the ASD, wherein the adsorbent is SiO2.

141. The pharmaceutical composition of claim 124, wherein the ASD comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 10 wt % to about 30 wt % of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 30 wt % of the ASD, wherein the hydrophilic polymer is HPMC, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS or lecithin or a combination thereof; d) an organic acid in an amount from about 10% to about 30% by weight of the ASD, wherein the organic acid is tartaric acid; and e) an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

142. The pharmaceutical composition of claim 124, wherein the ASD consists of: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 10 wt % to about 30 wt % of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 30 wt % of the ASD, wherein the hydrophilic polymer is HPMC, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS or lecithin or a combination thereof; d) an organic acid in an amount from about 10% to about 30% by weight of the ASD, wherein the organic acid is tartaric acid; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

143. The pharmaceutical composition of claim [0012], wherein the ASD comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 40 wt % of the ASD; b) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; c) a surfactant, the surfactant being present in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 40% by weight of the ASD; and e) an adsorbent in an amount ranging from about 15 wt % to about 40 wt % of the ASD.

144. The pharmaceutical composition of claim 143, wherein the ASD comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 40 wt % of the ASD; b) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD, wherein the hydrophilic polymer comprises HPMC; c) a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 15% to about 30% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

145. The pharmaceutical composition of claim [0012], wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 30 mg to about 400 mg; b) a hydrophilic polymer in an amount of about 30 mg to about 800 mg, based on the weight of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, or a combination thereof; c) a surfactant in an amount of about 30 mg to about 400 mg, wherein the surfactant is TPGS or lecithin or a combination thereof; d) optionally an organic acid in an amount of about 30 mg to about 400 mg, wherein the organic acid is tartaric acid; and e) optionally an adsorbent in an amount of about 30 mg to about 150 mg, wherein the adsorbent is SiO2.

146. The pharmaceutical composition of claim 145, wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 30 mg to about 200 mg; b) a hydrophilic polymer in an amount of about 30 mg to about 300 mg, based on the weight of the ASD, wherein the hydrophilic polymer is HPMC, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, or a combination thereof; c) a surfactant in an amount of about 30 mg to about 250 mg, wherein the surfactant is TPGS or lecithin or a combination thereof; d) optionally an organic acid in an amount of about 30 mg to about 200 mg, wherein the organic acid is tartaric acid; and e) optionally an adsorbent in an amount of about 40 mg to about 250 mg, wherein the adsorbent is SiO2.

147. An amorphous solid dispersion (ASD), wherein the amorphous solid dispersion comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof; b) hydrophilic polymer; c) surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

148. The ASD of claim 128, wherein the ASD comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof; b) a hydrophilic polymer, wherein the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone or a combination thereof; c) a surfactant, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (e.g., caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, or a combination thereof; d) optionally an organic acid, wherein the organic acid is tartaric acid; and e) optionally an adsorbent, wherein the adsorbent is SiO2.

149. The ASD of claim 129, wherein the ASD comprises: a) pazopanib free base or a pharmaceutically acceptable salt thereof, wherein the amount of pazopanib free base or a pharmaceutically acceptable salt thereof is about 5 wt % to about 40 wt % of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 70 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS or lecithin or a combination thereof; d) optionally an organic acid in an amount from about 10% to about 40% by weight of the ASD, wherein the organic acid is tartaric acid; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

150. according to the pharmaceutical composition described in any one of claims 124 to 130, wherein after oral administration under fasting conditions, the AUC last When measured, the pharmaceutical composition exhibits a bioavailability that is about 40% to about 180% of the bioavailability of a corresponding reference formulation comprising pazopanib hydrochloride, wherein the reference pharmaceutical composition does not comprise an amorphous solid dispersion, and wherein the dose of the reference formulation is at least 2 times the dose of the pharmaceutical composition.

151. according to the pharmaceutical composition described in any one of claims 124 to 130, wherein after oral administration under fasting conditions, C max When measured, the pharmaceutical composition exhibits a bioavailability that is about 50% to about 200% of the bioavailability of a corresponding reference formulation comprising pazopanib hydrochloride, wherein the reference pharmaceutical composition does not comprise an amorphous solid dispersion, and wherein the dose of the reference formulation is at least 2 times the dose of the pharmaceutical composition.

152. A method of treating a disease or condition, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0012], 10, or 124 to 132.

153. A method for treating cancer, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0012], 10, or 124 to 132.

154. The method of claim 134, wherein the cancer is a solid tumor.

155. The method of claim 135, wherein the solid tumor is a soft tissue sarcoma.

156. The method of claim 136, wherein the soft tissue sarcoma is an advanced soft tissue sarcoma.

157. The method of claim 134, wherein the cancer is renal cancer.

158. The method of claim 138, wherein the renal cancer is advanced renal cell carcinoma.

159. A method for inhibiting tyrosine kinase of a VEGF receptor (VEGFR) and / or a PDGF receptor (PDGFR), the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0012], 10, or 124 to 132.

160. The method of any one of claims 133 to 140, wherein the subject is an adult.

161. The method of any one of claims 133 to 137, wherein the subject previously received chemotherapy.

162. The pharmaceutical composition of claim [0013], wherein the ASD comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is from about 3% to about 50% by weight of the ASD; b) a hydrophilic polymer in an amount from about 10 wt % to about 70 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof; d) an organic acid in an amount from about 10% to about 40% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

163. The pharmaceutical composition of claim 143, wherein the ASD comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is about 5% to about 40% by weight of the ASD; b) a hydrophilic polymer in an amount from about 1 wt % to about 80 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof; c) a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof; d) an organic acid in an amount from about 10% to about 40% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

164. The pharmaceutical composition of claim 143, wherein the ASD comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is from about 10% to about 30% by weight of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 30 wt % of the ASD, wherein the hydrophilic polymer is HPMC-E5, HPMCAS, PVP or PVP / VA or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, lecithin, or a combination thereof; d) an organic acid in an amount from about 10% to about 30% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

165. The pharmaceutical composition of claim 143, wherein the ASD consists of: a) lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is from about 10% to about 30% by weight of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 30 wt % of the ASD, wherein the hydrophilic polymer is HPMC-E5, HPMCAS, PVP or PVP / VA or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, lecithin, or a combination thereof; d) an organic acid in an amount from about 10% to about 30% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

166. The pharmaceutical composition of claim [0013], wherein the ASD comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is from about 3% to about 50% by weight of the ASD; b) a hydrophilic polymer in an amount ranging from about 1 wt % to about 80 wt % of the ASD; c) a surfactant, the surfactant being present in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 40% by weight of the ASD; and e) an adsorbent in an amount ranging from about 15 wt % to about 40 wt % of the ASD.

167. The pharmaceutical composition of claim 166, wherein the ASD comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is about 5% to about 40% by weight of the ASD; b) a hydrophilic polymer in an amount of about 1 wt % to about 80 wt % of the ASD, wherein the hydrophilic polymer comprises HPMC, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, polymethacrylate, or a combination thereof; c) a surfactant in an amount of about 5 wt % to about 60 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 40% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

168. The pharmaceutical composition of claim [0013], wherein the pharmaceutical composition is formulated in a unit dosage form, the unit dosage form comprising: a) lurasidone free base or a pharmaceutically acceptable salt thereof in an amount of about 20 mg to about 120 mg (e.g., 20, 40, 60, 80 or 120 mg); b) a hydrophilic polymer in an amount of about 20 mg to about 400 mg, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, PVP / VA, HPMC AS, PVP or a combination thereof; c) a surfactant in an amount of about 20 mg to about 120 mg, wherein the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof; d) an organic acid in an amount of about 20 mg to about 120 mg, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally an adsorbent in an amount of about 30 mg to about 180 mg, wherein the adsorbent is SiO2.

169. The pharmaceutical composition of claim 145, wherein the pharmaceutical composition is formulated in a unit dosage form comprising: a) lurasidone free base or a pharmaceutically acceptable salt thereof in an amount of about 20 mg to about 60 mg; b) a hydrophilic polymer in an amount of about 20 mg to about 160 mg, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMCAS, PVP, or a combination thereof; c) a surfactant in an amount of about 20 mg to about 60 mg, wherein the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof; d) optionally an organic acid in an amount of about 20 mg to about 60 mg, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally an adsorbent in an amount of about 30 mg to about 80 mg, wherein the adsorbent is SiO2.

170. An amorphous solid dispersion (ASD), wherein the amorphous solid dispersion comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof; b) hydrophilic polymer; c) surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

171. The ASD of claim 170, wherein the ASD comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof; b) a hydrophilic polymer, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP or a combination thereof; c) a surfactant, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (e.g., caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, or a combination thereof; d) optionally an organic acid, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally an adsorbent, wherein the adsorbent is SiO2.

172. The ASD of claim 148, wherein the ASD comprises: a) lurasidone free base or a pharmaceutically acceptable salt thereof, wherein the amount of lurasidone free base or a pharmaceutically acceptable salt thereof is from about 5% to about 50% by weight of the ASD; b) a hydrophilic polymer in an amount from about 10 wt % to about 70 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof; d) optionally an organic acid in an amount of about 10% to about 40% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

173. according to the pharmaceutical composition described in any one of claims 143 to 149, wherein after oral administration under fasting conditions, the AUC last When measured, the pharmaceutical composition exhibits a bioavailability that is about 300% to about 1000% of the bioavailability of a corresponding reference formulation comprising lurasidone hydrochloride, wherein the reference pharmaceutical composition does not comprise the amorphous solid dispersion.

174. according to the pharmaceutical composition described in any one of claims 143 to 149, wherein after oral administration under fasting conditions, C max When measured, the pharmaceutical composition exhibits a bioavailability that is about 500% to about 1500% of the bioavailability of a corresponding reference formulation comprising lurasidone hydrochloride, wherein the reference pharmaceutical composition does not comprise the amorphous solid dispersion.

175. A method of treating a disease or condition, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0013], 10, or 143 to 151.

176. A method for treating a mental disorder, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0013], 10, or 143 to 151.

177. The method of claim 153, wherein the psychiatric disorder is schizophrenia.

178. The method of claim 153, wherein the psychiatric disorder is depression.

179. The method of claim 155, wherein the depression is associated with bipolar I disorder.

180. The method of claim 155, wherein the depression is bipolar depression.

181. A method of inhibiting central dopamine D2 and type 2 serotonin (5HT2A) receptors, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0013], 10, or 143 to 151.

182. The method of any one of claims 152 to 158, wherein the subject is an adult.

183. The method of any one of claims 152 to 154, wherein the subject is a teenager, wherein the teenager is between 13 and 17 years old.

184. The method of any one of claims 152-153 or 155-158, further comprising administering an anticonvulsant.

185. The method of claim 161, wherein the anticonvulsant is lithium or valproate.

186. The pharmaceutical composition of claim [0015], wherein the ASD comprises: a) vilazodone free base or a pharmaceutically acceptable salt thereof, wherein the vilazodone free base or a pharmaceutically acceptable salt thereof is present in an amount of about 5% to about 50% by weight of the ASD; b) a hydrophilic polymer in an amount ranging from about 5% to about 70% by weight of the ASD; c) a surfactant, the surfactant being present in an amount of about 10 wt % to about 50 wt % of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 35% by weight of the ASD; and e) optionally, an adsorbent in an amount ranging from about 15% to about 40% by weight of the ASD.

187. The pharmaceutical composition of claim 186, wherein the ASD comprises: a) vilazodone free base or a pharmaceutically acceptable salt thereof, wherein the vilazodone free base or a pharmaceutically acceptable salt thereof is present in an amount of about 5% to about 50% by weight of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 40 wt % of the ASD, wherein the hydrophilic polymer comprises HPMC, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, copovidone, polymethacrylate, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene glyceride, polysorbate, or a combination thereof; d) an organic acid in an amount from about 10% to about 35% by weight of the ASD, wherein the organic acid is tartaric acid or citric acid or a combination thereof; and e) optionally, an adsorbent in an amount of about 15 wt % to about 40 wt % of the ASD, wherein the adsorbent is SiO2.

188. The pharmaceutical composition of claim [0015], wherein the ASD comprises: a) vilazodone free base or a pharmaceutically acceptable salt thereof, wherein the vilazodone free base or a pharmaceutically acceptable salt thereof is in an amount of about 5% to about 40% by weight of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 70 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS or lecithin or a combination thereof; and d) an organic acid in an amount of about 10% to about 40% by weight of the ASD, wherein the organic acid is citric acid.

189. The pharmaceutical composition of claim 188, wherein the ASD comprises: a) vilazodone free base or a pharmaceutically acceptable salt thereof, wherein the vilazodone free base or a pharmaceutically acceptable salt thereof is present in an amount of about 15% to about 30% by weight of the ASD; b) a hydrophilic polymer in an amount of about 15 wt % to about 60 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, or a combination thereof; c) a surfactant in an amount of about 15% to about 30% by weight of the ASD, wherein the surfactant is TPGS or lecithin or a combination thereof; and d) an organic acid in an amount of about 15% to about 30% by weight of the ASD, wherein the organic acid is citric acid.

190. The pharmaceutical composition of claim [0015], wherein the pharmaceutical composition is formulated in a unit dosage form, the unit dosage form comprising: a) vilazodone free base or a pharmaceutically acceptable salt thereof, wherein the vilazodone free base or a pharmaceutically acceptable salt thereof is in an amount of about 5 mg to about 100 mg; b) a hydrophilic polymer in an amount of about 10 mg to about 300 mg, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMCAS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, PVP, or a combination thereof; c) a surfactant in an amount of about 5 mg to about 100 mg, wherein the surfactant is TPGS or lecithin or a combination thereof; and d) an organic acid in an amount of about 5 mg to about 100 mg, wherein the organic acid is citric acid.

191. An amorphous solid dispersion (ASD), wherein the amorphous solid dispersion comprises: a) vilazodone free base or a pharmaceutically acceptable salt thereof; b) hydrophilic polymer; c) surfactant; d) optionally an organic acid; and e) optionally an adsorbent.

192. The ASD of claim 191, wherein the ASD comprises: a) vilazodone free base or a pharmaceutically acceptable salt thereof; b) a hydrophilic polymer, wherein the hydrophilic polymer is HPMC (such as HPMC-E5), polymethacrylate, PVP / VA, HPMC AS, PVP or a combination thereof; c) a surfactant, wherein the surfactant comprises a phospholipid or a derivative thereof, such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS, a graft copolymer based on polyvinyl acetate and polyvinyl caprolactam, polyoxyethylene hydrogenated castor oil, polyoxyethylene glyceride (e.g., caprylocaproyl polyoxyethylene-8 glyceride), polysorbate, or a combination thereof; and d) an organic acid, wherein the organic acid is citric acid.

193. The ASD of claim 166, wherein the ASD comprises: a) vilazodone free base or a pharmaceutically acceptable salt thereof, wherein the vilazodone free base or a pharmaceutically acceptable salt thereof is in an amount of about 5% to about 40% by weight of the ASD; b) a hydrophilic polymer in an amount of about 10 wt % to about 60 wt % of the ASD, wherein the hydrophilic polymer is HPMC, polymethacrylate, PVP / VA, HPMC AS, PVP, or a combination thereof; c) a surfactant in an amount of about 10% to about 40% by weight of the ASD, wherein the surfactant is TPGS, PEG, a block copolymer of polyethylene glycol and polypropylene glycol, polyoxyethylene hydrogenated castor oil, lecithin, or a combination thereof; and d) an organic acid in an amount of about 10% to about 40% by weight of the ASD, wherein the organic acid is citric acid.

194. according to the pharmaceutical composition described in any one of claims 163 to 167, wherein when after oral administration, the AUC last When measured, the pharmaceutical composition exhibits a bioavailability that is about 130% to about 500% of the bioavailability of a corresponding reference formulation comprising vilazodone hydrochloride, wherein the reference pharmaceutical composition does not comprise the amorphous solid dispersion.

195. according to the pharmaceutical composition described in any one of claims 163 to 167, wherein when after oral administration with C max When measured, the pharmaceutical composition exhibits a bioavailability that is about 115% to about 600% of the bioavailability of a corresponding reference formulation comprising vilazodone hydrochloride, wherein the reference pharmaceutical composition does not comprise the amorphous solid dispersion.

196. A method of treating a disease or condition, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0015], 10, or 163 to 169.

197. A method for treating a mental disorder, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0015], 10, or 163 to 169.

198. The method of claim 171, wherein the psychiatric disorder is major depressive disorder.

199. A method of inhibiting a serotonin (5-HT1A) receptor, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims 9, 10, or 170 to 172.

200. A method of stimulating a serotonin transporter, the method comprising administering to a subject in need thereof a pharmaceutical composition or amorphous solid dispersion according to any one of claims [0015], 10, or 170 to 172.

201. The method of claim 174, wherein the stimulation is performed by partial excitation.

202. The method of any one of claims 170 to 175, wherein the subject is an adult.

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