Compositions comprising alkyne substituted quinazoline derivatives and related uses

Abstract

The present disclosure relates to formulations comprising Compound No. 1: (Compound No. 1) or a pharmaceutically acceptable salt thereof. The present disclosure also relates to uses of the formulations, e.g., in treating or preventing cancer.

Description

COMPOSITIONS COMPRISING ALKYNE SUBSTITUTED QUINAZOLINEDERIVATIVES AND RELATED USESRELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, U.S. Provisional Application No. 63 / 613.531 filed December 21, 2023, which is hereby incorporated by reference in its entirety for all purposes.BACKGROUND

[0002] Mutations affecting either the intracellular catalytic domain or extracellular ligand binding domain of an ErbB receptor can generate oncogenic activity (the ErbB protein family consists of 4 members including ErbB-1, also named epidermal growth factor receptor (EGFR) and Erb-2, also named HER2 in humans). ErbB inhibitors are a known treatment for a number of cancers. However, not every patient is responsive satisfactorily to this treatment. Thus, there is a long-felt need in the art for new therapies that are able to address the variable responsiveness of cancer patients to known therapies.

[0003] There is a need for formulations that could be used in preventing or treating cancer in patients, e.g.. with these oncogenic mutations. The present disclosure addresses this need.SUMMARY

[0004] In some aspects, the present disclosure provides a formulation (e.g., an oral formulation) comprising Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0005] In some aspects, the present disclosure provides a method of inhibiting an oncogenic variant of an ErbB receptor in a subject, comprising administering to the subject a formulation disclosed herein

[0006] In some aspects, the present disclosure provides a formulation disclosed herein for use in inhibiting an oncogenic variant of an ErbB receptor in a subject.

[0007] In some aspects, the present disclosure provides a method of treating or preventing cancer in a subject, comprising administering to the subject a formulation disclosed herein.

[0008] In some aspects, the present disclosure provides a formulation disclosed herein for use in treating or preventing cancer in a subject.

[0009] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosurebelongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods and examples are illustrative only and are not intended to be limiting. In the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures will control.

[0010] Other features and advantages of the disclosure will be apparent from the following detailed description and claims.BRIEF DESCRIPTIONS OF FIGURES

[0011] FIG. 1 is a graph showing an exemplary scheme of preparing capsules disclosed herein.

[0012] FIGS. 2A-2C are a set of graphs showing exemplary schemes of preparing tablets disclosed herein. FIG. 2A describes the exemplary process to prepare a common blend. FIG.2B and 2C describes exemplary processes to use the common blend to prepare 75 mg and 100 mg tablets, respectively.DETAILED DESCRIPTIONCompounds of the Present Disclosure

[0013] It is understood that, as used herein, the term “Compound No. 1” refers to a compound having the following structure:(Compound No. 1).

[0014] It is understood that the term “Compound No. 1 A,’" as used herein, refers to a compound having the following structure:

[0015] It is understood that the term “Compound No. IB,’" as used herein, refers to a compound having the following structure:(Compound No. IB)Formulations of the Present Disclosure

[0016] In some aspects, the present disclosure provides a formulation (e.g., an oral formulation) comprising Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0017] In some embodiments, the formulation comprises Compound No. 1.

[0018] In some embodiments, the formulation comprises Compound No. 1A, Compound No. IB, or a pharmaceutically acceptable salt thereof.

[0019] In some embodiments, the formulation comprises Compound No. 1 A and / or Compound No. IB.

[0020] In some embodiments, the formulation comprises Compound No. 1A and Compound No. IB.

[0021] In some embodiments, the formulation comprises Compound No. 1A or a pharmaceutically acceptable salt thereof.

[0022] In some embodiments, the formulation comprises Compound No. 1 A.

[0023] In some embodiments, the formulation comprises Compound No. IB or a pharmaceutically acceptable salt thereof.

[0024] In some embodiments, the formulation comprises Compound No. IB.

[0025] In some embodiments, the formulation is an oral formulation.

[0026] In some embodiments, the formulation is a capsule or a tablet.

[0027] In some embodiments, the formulation is a capsule.

[0028] In some embodiments, the formulation is a tablet.Capsules

[0029] In some embodiments, the formulation (e.g., capsule) comprises Compound No. 1 or the pharmaceutically acceptable salt thereof.

[0030] In some embodiments, the formulation (e.g., capsule) comprises Compound No. 1.

[0031] In some embodiments, the formulation (e.g., capsule) comprises Compound No. 1 A.

[0032] In some embodiments, the formulation (e g., capsule) comprises Compound No. IB.

[0033] In some embodiments, the formulation (e.g., capsule) further comprises: one or more of a filler, a disintegrant, a glidant. and a lubricant.

[0034] In some embodiments, the formulation (e.g., capsule) further comprises a filler.

[0035] In some embodiments, the formulation (e.g., capsule) further comprises a disintegrant.

[0036] In some embodiments, the formulation (e.g., capsule) further comprises a glidant.

[0037] In some embodiments, the formulation (e.g., capsule) further comprises a lubricant.

[0038] In some embodiments, the formulation (e g., capsule) further comprises a filler, a disintegrant, a glidant, and a lubricant.

[0039] In some embodiments, the formulation (e.g., capsule) comprises about 5.6±2.0% w / w, about 5.6±1.5% w / w, about 5.6±1.0% w / w, about 5.6±0.9% w / w, about 5.6±0.8% w / w, about 5.6±0.7% w / w, about 5.6±0.6% w / w, about 5.6±0.5% w / w. about 5.6±0.4% w / w, about 5.6±0.3% w / w, about 5.6±0.2% w / w, or about 5.6±0.1% w / w (e.g., about 5.6% w / w) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1 A and / or Compound No. IB)).

[0040] In some embodiments, the formulation (e.g., capsule) comprises about 5.0±2.0 mg, about 5.0±1.5 mg, about 5.0±1.0 mg, about 5.0±0.9 mg, about 5.0±0.8 mg. about 5.0±0.7 mg, about 5.0±0.6 mg, about 5.0±0.5 mg, about 5.0±0.4 mg, about 5.0±0.3 mg, about 5.0±0.2 mg,or about 5.0±0.1 mg (e.g., about 5.0 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A or Compound No. IB)).

[0041] In some embodiments, the formulation (e.g., capsule) comprises about 27.8±5.0% w / w, about 27.8±4.0% w / w, about 27.8±3.0% w / w, about 27.8±2.0% w / w, about 27.8±1.5% w / w, about 27.8±1.0% w / w, about 27.8±0.9% w / w, about 27.8±0.8% w / w, about 27.8±0.7% w / w, about 27.8±0.6% w / w. about 27.8±0.5% w / w, about 27.8±0.4% w / w, about 27.8±0.3% w / w, about 27.8±0.2% w / w. or about 27.8±0. 1% w / w (e.g., about 27.8% w / w) of CompoundNo. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1 A and / or Compound No. IB)).

[0042] In some embodiments, the formulation (e.g., capsule) comprises about 25±5.0 mg, about 25±4.0 mg, about 25±3.0 mg, about 25±2.0 mg, about 25±1.5 mg. about 25±1.0 mg, about 25±0.9 mg, about 25±0.8 mg, about 25±0.7 mg, about 25±0.6 mg, about 25±0.5 mg, about 25±0.4 mg, about 25±0.3 mg, about 25±0.2 mg, or about 25±0.1 mg (e.g., about 25 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A and / or Compound No. IB)).

[0043] In some embodiments, the formulation (e.g.. capsule) comprises about 40±15% w / w. about 40±10% w / w, about 40±5.0% w / w, about 40±4.0% w / w, about 40±3.0% w / w, about 40±2.0% w / w, about 40±1.5% w / w, about 40±1.0% w / w, about 40±0.9% w / w, about 40±0.8% w / w, about 40±0.7% w / w, about 40±0.6% w / w, about 40±0.5% w / w, about 40±0.4% w / w, about 40±0.3% w / w, about 40±0.2% w / w, or about 40±0. I% w / w (e.g.. about 40% w / w) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1 A and / or Compound No. IB)).

[0044] In some embodiments, the formulation (e.g., capsule) comprises about 100±15 mg, about 100±10 mg, about 100±5.0 mg, about 100±4.0 mg, about 100±3.0 mg, about 100±2.0 mg, about 100±1.5 mg, about 100±1.0 mg, about 100±0.9 mg, about 100±0.8 mg, about 100±0.7 mg, about 100±0.6 mg, about 100±0.5 mg, about 100±0.4 mg, about 100±0.3 mg, about 100+0.2 mg, or about 100+0.1 mg (e.g., about 100 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A and / or Compound No. IB)).Fillers

[0045] In some embodiments, the filler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or cellulose.

[0046] In some embodiments, the filler comprises cellulose.

[0047] In some embodiments, the filler comprises microcrystalline cellulose.

[0048] In some embodiments, the formulation (e.g., capsule) comprises about 90.4+15% w / w, about 90.4+ 10% w / w, about 90.4+5.0% w / w, about 90.4+4.0% w / w, about 90.4+3.0% w / w, about 90.4+2.0% w / w, about 90.4+1.5% w / w, about 90.4+1.0% w / w, about 90.4+0.9% w / w, about 90.4+0.8% w / w. about 90.4+0.7% w / w, about 90.4+0.6% w / w, about 90.4+0.5% w / w, about 90.4+0.4% w / w. about 90.4+0.3% w / w. about 90.4+0.2% w / w, or about 90.4+0.1% w / w (e.g., about 90.4% w / w) of the filler (e.g., microcrystalline cellulose).

[0049] In some embodiments, the formulation (e.g., capsule) comprises about 81.4+15 mg, about 81.4+10 mg, about 81.4+5.0 mg, about 81.4+4.0 mg, about 81.4+3.0 mg, about 81.4+2.0 mg, about 81.4+1.5 mg. about 81.4+1.0 mg, about 81.4+0.9 mg, about 81.4+0.8 mg, about 81.4+0.7 mg, about 81.4+0.6 mg, about 81.4+0.5 mg, about 81.4+0.4 mg, about 81.4+0.3 mg, about 81.4+0.2 mg, or about 81.4+0.1 mg (e.g., about 81.4 mg) of the filler (e.g., microcrystalline cellulose).

[0050] In some embodiments, the formulation (e.g., capsule) comprises about 68.2+15% w / w, about 68.2+10% w / w. about 68.2+5.0% w / w. about 68.2+4.0% w / w, about 68.2+3.0% w / w. about 68.2+2.0% w / w, about 68.2+1.5% w / w, about 68.2+1.0% w / w, about 68.2+0.9% w / w, about 68.2+0.8% w / w, about 68.2+0.7% w / w, about 68.2+0.6% w / w, about 68.2+0.5% w / w, about 68.2+0.4% w / w, about 68.2+0.3% w / w, about 68.2+0.2% w / w, or about 68.2+0.1% w / w (e.g.. about 68.2% w / w) of the filler (e.g., microcrystalline cellulose).

[0051] In some embodiments, the formulation (e.g., capsule) comprises about 61.4+15 mg, about 61.4+10 mg, about 61.4+5.0 mg, about 61.4+4.0 mg, about 61.4+3.0 mg, about 61.4+2.0 mg, about 61.4+1.5 mg, about 61.4+1.0 mg, about 61.4+0.9 mg, about 61.4+0.8 mg, about 61.4+0.7 mg. about 61.4+0.6 mg, about 61.4+0.5 mg. about 61.4+0.4 mg, about 61.4+0.3 mg, about 61.4+0.2 mg, or about 61.4+0.1 mg (e.g., about 61.4 mg) of the filler (e.g., microcrystalline cellulose).

[0052] In some embodiments, the formulation (e.g., capsule) comprises about 50+15% w / w, about 50+10% w / w, about 50+5.0% w / w, about 50+4.0% w / w, about 50+3.0% w / w, about 50+2.0% w / w, about 50+1.5% w / w, about 50+1.0% w / w, about 50+0.9% w / w, about 50+0.8% w / w, about 50+0.7% w / w, about 50+0.6% w / w, about 50+0.5% w / w, about 50+0.4% w / w, about 50+0.3% w / w, about 50+0.2% w / w, or about 50+0. 1% w / w (e.g., about 50% w / w) of the filler (e.g., microcrystalline cellulose).

[0053] In some embodiments, the formulation (e.g., capsule) comprises about 125+15 mg, about 125+10 mg, about 125+5.0 mg, about 125+4.0 mg, about 125+3.0 mg, about 125+2.0mg, about 125+1.5 mg, about 125+1.0 mg, about 125+0.9 mg, about 125+0.8 mg, about 125±0.7 mg, about 125±0.6 mg, about 125±0.5 mg, about 125±0.4 mg, about 125±0.3 mg, about 125+0.2 mg, or about 125+0.1 mg (e.g., about 125 mg) of the filler (e.g., microcrystalline cellulose).Disintegrants

[0054] In some embodiments, the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate, chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

[0055] In some embodiments, the disintegrant comprises a sodium salt.

[0056] In some embodiments, the disintegrant comprises sodium carboxymethylcellulose.

[0057] In some embodiments, the disintegrant comprises croscarmellose sodium.

[0058] In some embodiments, the formulation (e.g., capsule) comprises about 3.0+2.0% w / w, about 3.0+1.5% w / w, about 3.0+1.0% w / w, about 3.0+0.9% w / w, about 3.0±0.8% w / w, about3.0±0.7% w / w, about 3.0±0.6% w / w, about 3.0±0.5% w / w. about 3.0±0.4% w / w, about3.0+0.3% w / w, about 3.0+0.2% w / w, or about 3.0+0.1% w / w (e.g., about 3.0% w / w) of the disintegrant (e.g., croscarmellose sodium).

[0059] In some embodiments, the formulation (e.g., capsule) comprises about 2.7±2.0 mg, about 2.7+1.5 mg, about 2.7+1.0 mg, about 2.7+0.9 mg, about 2.7+0.8 mg. about 2.7+0.7 mg, about 2.7±0.6 mg, about 2.7+0.5 mg, about 2.7+0.4 mg, about 2.7+0.3 mg, about 2.7+0.2 mg, or about 2.7+0.1 mg (e.g., about 2.7 mg) of the disintegrant (e.g., croscarmellose sodium).

[0060] In some embodiments, the formulation (e.g., capsule) comprises about 8.0+5.0% w / w, about 8.0±4.0% w / w, about 8.0±3.0% w / w, about 8.0±2.0% w / w, about 8.0±1.5% w / w, about8.0±1.0% w / w, about 8.0±0.9% w / w, about 8.0±0.8% w / w, about 8.0±0.7% w / w, about8.0+0.6% w / w, about 8.0±0.5% w / w, about 8.0±0.4% w / w, about 8.0+0.3% w / w, about8.0±0.2% w / w, or about 8.0±0.1% w / w (e.g., about 8.0% w / w) of the disintegrant (e.g., croscarmellose sodium).

[0061] In some embodiments, the formulation (e.g., capsule) comprises about 20+5.0 mg. about 20+4.0 mg, about 20+3.0 mg, about 20+2.0 mg, about 20+1.5 mg, about 20+1.0 mg, about 20+0.9 mg, about 20+0.8 mg, about 20+0.7 mg, about 20±0.6 mg, about 20+0.5 mg, about 20±0.4 mg, about 20±0.3 mg, about 20±0.2 mg, or about 20±0.1 mg (e.g., about 20 mg) of the disintegrant (e.g., croscarmellose sodium).Glidants

[0062] In some embodiments, the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

[0063] In some embodiments, the glidant comprises silicon dioxide.

[0064] In some embodiments, the glidant comprises colloidal silicon dioxide.

[0065] In some embodiments, the formulation (e.g., capsule) comprises about 0.5±0.3% w / w. about 0.5±0.2% w / w, or about 0.5±0.1% w / w (e.g., about 0.5% w / w) of the glidant (e.g., colloidal silicon dioxide).

[0066] In some embodiments, the formulation (e.g., capsule) comprises about 0.5±0.3 mg, about 0.5±0.2 mg, or about 0.5±0. 1 mg (e.g.. about 0.5 mg) of the glidant (e.g., colloidal silicon dioxide).

[0067] In some embodiments, the formulation (e.g., capsule) comprises about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w (e.g., about 1.0% w / w) of the glidant (e.g., colloidal silicon dioxide).

[0068] In some embodiments, the formulation (e.g., capsule) comprises about 2.5±1.0 mg. about 2.5±0.9 mg, about 2.5±0.8 mg, about 2.5±0.7 mg, about 2.5±0.6 mg, about 2.5±0.5 mg, about 2.5±0.4 mg, about 2.5±0.3 mg, about 2.5±0.2 mg, or about 2.5±0.1 mg (e.g., about 2.5 mg) of the glidant (e g., colloidal silicon dioxide).Lubricants

[0069] In some embodiments, the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

[0070] In some embodiments, the lubricant comprises a magnesium salt.

[0071] In some embodiments, the lubricant comprises magnesium stearate.

[0072] In some embodiments, the formulation (e.g., capsule) comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w (e.g., about 0.5% w / w) of the lubricant (e.g., magnesium stearate).

[0073] In some embodiments, the formulation (e.g., capsule) comprises about 0.5±0.3 mg, about 0.5±0.2 mg, or about 0.5±0.1 mg (e.g., about 0.5 mg) (e.g., about 2.7 mg) of the lubricant (e.g., magnesium stearate).

[0074] In some embodiments, the formulation (e.g., capsule) comprises about I.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0. 1% w / w (e.g., about 1.0% w / w) of the lubricant (e.g., magnesium stearate).

[0075] In some embodiments, the formulation (e.g., capsule) comprises about 2.5±1.0 mg, about 2.5±0.9 mg, about 2.5±0.8 mg, about 2.5±0.7 mg, about 2.5±0.6 mg, about 2.5±0.5 mg, about 2.5±0.4 mg, about 2.5±0.3 mg, about 2.5±0.2 mg, or about 2.5±0.1 mg (e.g., about 2.5 mg) of the lubricant (e.g., magnesium stearate).Exemplary Embodiments

[0076] In some embodiments, the formulation (e.g., capsule) comprises one or more of the ingredients described in Table Al.Table Al

[0077] In some embodiments, the formulation (e.g., capsule) comprises one or more of the ingredients described in Table A2.Table A2

[0078] In some embodiments, the formulation (e.g., capsule) comprises one or more of the ingredients described in Table A3.Table A3

[0079] In some embodiments, the formulation (e.g., capsule) comprises one or more of the ingredients described in Table A4.Table A4

[0080] In some embodiments, the formulation (e.g., capsule) comprises one or more of the ingredients described in Table A5.Table A5

[0081] In some embodiments, the formulation (e.g.. capsule) comprises one or more of the ingredients described in Table A6.Table A6

[0082] In some embodiments, the formulation (e.g., capsule) is selected from the formulations described in Table 1.Tablets

[0083] In some embodiments, the formulation (e.g., tablet) comprises Compound No. 1 or the pharmaceutically acceptable salt thereof.

[0084] In some embodiments, the formulation (e.g., tablet) comprises an intragranular mixture.

[0085] In some embodiments, the formulation (e.g., tablet) comprises an extragranular mixture.

[0086] In some embodiments, the formulation (e.g., tablet) comprises an intragranular mixture and an extragranular mixture.

[0087] In some embodiments, the formulation (e.g., tablet) comprises Compound No. 1.

[0088] In some embodiments, the formulation (e g., tablet) comprises Compound No. 1A.

[0089] In some embodiments, the formulation (e.g., tablet) comprises Compound No. IB.

[0090] In some embodiments, the formulation (e g., tablet) further comprises a filler.

[0091] In some embodiments, the formulation (e.g., tablet) further comprises a disintegrant.

[0092] In some embodiments, the formulation (e.g., tablet) further comprises a glidant.

[0093] In some embodiments, the formulation (e.g., tablet) further comprises a lubricant.

[0094] In some embodiments, the formulation (e.g., tablet) further comprises a binder.

[0095] In some embodiments, the formulation (e.g.. tablet) further comprises a filler, a disintegrant, a glidant. a lubricant, and a binder.

[0096] In some embodiments, the formulation (e.g., tablet) comprises about 30.8±10% w / w, about 30.8±5.0% w / w, about 30.8±4.0% w / w, about 30.8±3.0% w / w, about 30.8±2.0% w / w, about 30.8±1.5% w / w, about 30.8±1.0% w / w, about 30.8±0.9% w / w, about 30.8±0.8% w / w, about 30.8±0.7% w / w. about 30.8±0.6% w / w, about 30.8±0.5% w / w, about 30.8±0.4% w / w, about 30.8±0.3% w / w, about 30.8±0.2% w / w, or about 30.8±0.1 % w / w (e.g., about 30.8% w / w) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A and / or Compound No. IB)).

[0097] In some embodiments, the formulation (e.g., tablet) comprises about 75±15 mg, about 75±10 mg, about 75±5.0 mg, about 75±4.0 mg, about 75±3.0 mg, about 75±2.0 mg, about 75±1.5 mg, about 75±1.0 mg, about 75±0.9 mg, about 75±0.8 mg, about 75±0.7 mg, about 75±0.6 mg, about 75±0.5 mg, about 75±0.4 mg, about 75±0.3 mg, about 75±0.2 mg, or about 75±0.1 mg (e.g., about 75 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g.. Compound No. 1 (e.g.. Compound No. 1 A and / or Compound No. IB)).

[0098] In some embodiments, the formulation (e g., tablet) comprises about 100±15 mg, about 100±10 mg, about 100±5.0 mg, about 100±4.0 mg, about 100±3.0 mg, about 100±2.0 mg, about 100±1.5 mg. about 100±1.0 mg, about 100±0.9 mg, about 100±0.8 mg, about 100±0.7 mg, about 100±0.6 mg. about 100±0.5 mg, about 100±0.4 mg, about 100±0.3 mg, about 100±0.2 mg, or about 100±0. 1 mg (e.g., about 100 mg) of Compound No. 1 or thepharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A and / or Compound No. IB)).

[0099] In some embodiments, the formulation (e.g., tablet) comprises about 200±40 mg, about 200±30 mg, about 200±20 mg, about 200±15 mg, about 200±10 mg, about 200+5.0 mg, about 200±4.0 mg, about 200+3.0 mg, about 200±2.0 mg, about 200+1.5 mg, about 200+1.0 mg, about 200±0.9 mg. about 200±0.8 mg, about 200±0.7 mg, about 200±0.6 mg, about 200±0.5 mg, about 200+0.4 mg. about 200+0.3 mg. about 200±0.2 mg. or about 200+0. 1 mg (e.g., about 200 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A and / or Compound No. IB)).

[0100] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 30.8±10% w / w, about 30.8+5.0% w / w, about 30.8±4.0% w / w, about 30.8+3.0% w / w, about 30.8±2.0% w / w, about 30.8+1.5% w / w, about 30.8+1.0% w / w, about 30.8+0.9% w / w, about 30.8+0.8% w / w, about 30.8+0.7% w / w, about 30.8±0.6% w / w, about 30.8+0.5% w / w, about 30.8±0.4% w / w, about 30.8±0.3% w / w, about 30.8±0.2% w / w, or about 30.8+0.1% w / w (e.g.. about 30.8% w / w) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g.. Compound No. 1 A and / or Compound No. IB)).

[0101] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 75±15 mg, about 75±10 mg, about 75+5.0 mg, about 75±4.0 mg, about 75+3.0 mg, about 75+2.0 mg, about 75+1.5 mg, about 75+1.0 mg, about 75+0.9 mg, about 75±0.8 mg, about 75+0.7 mg, about 75+0.6 mg, about 75+0.5 mg, about 75+0.4 mg, about 75+0.3 mg, about 75+0.2 mg, or about 75+0.1 mg (e.g., about 75 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A and / or Compound No. IB)).

[0102] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 100+15 mg, about 100+10 mg, about 100+5.0 mg, about 100+4.0 mg, about 100±3.0 mg, about 100+2.0 mg, about 100±1.5 mg, about 100+1.0 mg, about 100±0.9 mg, about 100±0.8 mg. about 100±0.7 mg, about 100±0.6 mg, about 100±0.5 mg, about 100±0.4 mg, about 100±0.3 mg. about 100+0.2 mg, or about 100+0.1 mg (e.g., about 100 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1 A and / or Compound No. IB)).

[0103] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 200±40 mg, about 200±30 mg, about 200±20 mg, about 200±15 mg, about 200±10 mg, about 200+5.0 mg, about 200+4.0 mg, about 200+3.0 mg, about 200+2.0 mg,about 200+1.5 mg. about 200+1.0 mg, about 200+0.9 mg, about 200+0.8 mg, about 200+0.7 mg, about 200±0.6 mg. about 200+0.5 mg, about 200+0.4 mg, about 200±0.3 mg, about 200±0.2 mg, or about 200±0. 1 mg (e.g., about 200 mg) of Compound No. 1 or the pharmaceutically acceptable salt thereof (e.g., Compound No. 1 (e.g., Compound No. 1A and / or Compound No. IB)).Fillers

[0104] In some embodiments, the filler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, cellulose, or any combination thereof.

[0105] In some embodiments, the filler comprises cellulose.

[0106] In some embodiments, the filler comprises microcrystalline cellulose.

[0107] In some embodiments, the formulation (e.g., tablet) comprises about 31.6+10% w / w, about 31.6+5.0% w / w. about 31.6+4.0% w / w, about 31.6±3.0% w / w, about 31.6+2.0% w / w, about 31.6+1.5% w / w. about 31.6+1.0% w / w, about 31.6+0.9% w / w, about 31.6+0.8% w / w. about 31.6+0.7% w / w, about 31.6+0.6% w / w, about 31.6+0.5% w / w, about 31.6+0.4% w / w, about 31.6+0.3% w / w, about 31.6+0.2% w / w, or about 31.6+0.1% w / w (e.g., about 31.6% w / w) of the filler (e.g., microcrystalline cellulose).

[0108] In some embodiments, the formulation (e.g., tablet) comprises about 77±15 mg, about 77+10 mg, about 77±5.0 mg, about 77+4.0 mg, about 77+3.0 mg, about 77±2.0 mg, about 77+1.5 mg, about 77+1.0 mg, about 77±0.9 mg, about 77+0.8 mg, about 77+0.7 mg, about 77+0.6 mg, about 77+0.5 mg, about 77+0.4 mg, about 77+0.3 mg, about 77+0.2 mg. or about 77+0. 1 mg (e.g., about 77 mg) of the filler (e.g.. microcrystalline cellulose).

[0109] In some embodiments, the formulation (e.g., tablet) comprises about 103+20 mg, about 103+15 mg, about 103+10 mg, about 103+5.0 mg, about 103+4.0 mg, about 103+3.0 mg, about 103+2.0 mg, about 103+1.5 mg, about 103+1.0 mg, about 103+0.9 mg, about 103+0.8 mg, about 103+0.7 mg. about 103+0.6 mg, about 103+0.5 mg, about 103+0.4 mg, about 103+0.3 mg, about 103+0.2 mg, or about 103+0.1 mg (e.g., about 103 mg) of the filler (e.g.. microcrystalline cellulose).

[0110] In some embodiments, the formulation (e.g., tablet) comprises about 206+40 mg, about 206+30 mg, about 206+20 mg, about 206+15 mg, about 206+10 mg, about 206+5.0 mg, about 206+4.0 mg. about 206+3.0 mg, about 206+2.0 mg, about 206+1.5 mg, about 206+1.0 mg, about 206+0.9 mg, about 206+0.8 mg, about 206+0.7 mg, about 206+0.6 mg, about 206+0.5mg, about 206±0.4 mg. about 206±0.3 mg, about 206±0.2 mg, or about 206±0.1 mg (e.g., about 206 mg) of the fdler (e.g., microcrystalline cellulose).

[0111] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 31.6±10% w / w, about 31.6±5.0% w / w, about 31.6±4.0% w / w, about 31.6±3.0% w / w, about 31.6±2.0% w / w, about 31.6±1.5% w / w, about 31.6±1.0% w / w, about 31.6±0.9% w / w, about 31.6±0.8% w / w. about 31.6±0.7% w / w, about 31.6±0.6% w / w, about 31.6±0.5% w / w, about 31.6±0.4% w / w, about 31.6±0.3% w / w, about 31.6±0.2% w / w, or about 31.6±0.1% w / w (e.g., about 31.6% w / w) of the filler (e.g., microcrystalline cellulose).

[0112] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 77±15 mg, about 77±10 mg, about 77±5.0 mg, about 77±4.0 mg, about 77±3.0 mg, about 77±2.0 mg, about 77±1.5 mg, about 77±1.0 mg, about 77±0.9 mg, about 77±0.8 mg, about 77±0.7 mg, about 77±0.6 mg, about 77±0.5 mg, about 77±0.4 mg, about 77±0.3 mg, about 77±0.2 mg, or about 77±0.1 mg (e.g., about 77 mg) of the filler (e.g., microcrystalline cellulose).

[0113] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 103±20 mg, about 103±15 mg, about 103±10 mg, about 103±5.0 mg, about 103±4.0 mg, about 103±3.0 mg, about 103±2.0 mg, about 103±1.5 mg, about 103±1.0 mg, about 103±0.9 mg, about 103±0.8 mg, about 103±0.7 mg, about 103±0.6 mg, about 103±0.5 mg, about 103±0.4 mg. about 103±0.3 mg, about 103±0.2 mg, or about 103±0.1 mg (e.g., about 103 mg) of the filler (e.g., microcrystalline cellulose).

[0114] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 206±40 mg, about 206±30 mg, about 206±20 mg, about 206±15 mg, about 206±10 mg, about 206±5.0 mg, about 206±4.0 mg, about 206±3.0 mg, about 206±2.0 mg, about 206±1.5 mg. about 206±1.0 mg, about 206±0.9 mg, about 206±0.8 mg, about 206±0.7 mg, about 206±0.6 mg, about 206±0.5 mg, about 206±0.4 mg, about 206±0.3 mg, about 206±0.2 mg, or about 206±0.1 mg (e.g., about 206 mg) of the filler (e.g., microcrystalline cellulose).Disintegrants

[0115] In some embodiments, the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate, chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

[0116] In some embodiments, the disintegrant comprises a sodium salt.

[0117] In some embodiments, the disintegrant comprises sodium carboxymethylcellulose.

[0118] In some embodiments, the disintegrant comprises croscarmellose sodium.

[0119] In some embodiments, the formulation (e.g., tablet) comprises about 4.0±2.0% w / w, about 4.0±1.5% w / w, about 4.0±1.0% w / w, about 4.0±0.9% w / w, about 4.0±0.8% w / w, about 4.0±0.7% w / w, about 4.0±0.6% w / w, about 4.0±0.5% w / w, about 4.0±0.4% w / w, about 4.0±0.3% w / w, about 4.0±0.2% w / w, or about 4.0±0.1% w / w (e.g., about 4.0% w / w) of the disintegrant (e.g., croscarmellose sodium).

[0120] In some embodiments, the formulation (e g., tablet) comprises about 9.6±4.0 mg, about 9.6±3.0 mg, about 9.6±2.0 mg, about 9.6±1.5 mg, about 9.6±1.0 mg, about 9.6±0.9 mg, about 9.6±0.8 mg, about 9.6±0.7 mg, about 9.6±0.6 mg, about 9.6±0.5 mg, about 9.6±0.4 mg, about 9.6±0.3 mg, about 9.6±0.2 mg, or about 9.6±0.1 mg (e.g.. about 9.6 mg) of the disintegrant (e.g., croscarmellose sodium).

[0121] In some embodiments, the formulation (e.g., tablet) comprises about 13±5.0 mg, about 13±4.0 mg, about 13±3.0 mg, about 13±2.0 mg, about 13±1.5 mg, about 13±1.0 mg, about 13±0.9 mg, about 13±0.8 mg. about 13±0.7 mg, about 13±0.6 mg, about 13±0.5 mg, about 13±0.4 mg. about 13±0.3 mg, about 13±0.2 mg. or about 13±0.1 mg (e.g., about 13 mg) of the disintegrant (e.g., croscarmellose sodium).

[0122] In some embodiments, the formulation (e.g., tablet) comprises about 26±10 mg, about 26±5.0 mg, about 26±4.0 mg. about 26±3.0 mg, about 26±2.0 mg, about 26±1.5 mg, about 26±1.0 mg, about 26±0.9 mg. about 26±0.8 mg. about 26±0.7 mg, about 26±0.6 mg, about 26±0.5 mg, about 26±0.4 mg, about 26±0.3 mg, about 26±0.2 mg, or about 26±0.1 mg (e.g., about 26 mg) of the disintegrant (e.g., croscarmellose sodium).

[0123] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 2.0±1.0% w / w. about 2.0±0.9% w / w, about 2.0±0.8% w / w, about 2.0±0.7% w / w, about 2.0±0.6% w / w, about 2.0±0.5% w / w, about 2.0±0.4% w / w, about 2.0±0.3% w / w, about 2.0±0.2% w / w, or about 2.0±0.1% w / w (e.g., about 2.0% w / w) of the disintegrant (e.g., croscarmellose sodium).

[0124] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 2.0±1.0% w / w. about 2.0±0.9% w / w, about 2.0±0.8% w / w. about 2.0±0.7% w / w, about 2.0±0.6% w / w, about 2.0±0.5% w / w, about 2.0±0.4% w / w, about 2.0±0.3% w / w, about 2.0±0.2% w / w, or about 2.0±0.1% w / w (e.g., about 2.0% w / w) of the disintegrant (e.g., croscarmellose sodium).

[0125] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 4.9±2.0 mg, about 4.9±1.5 mg, about 4.9±1.0 mg, about 4.9±0.9 mg, about4.9±0.8 mg, about 4.9±0.7 mg, about 4.9±0.6 mg, about 4.9±0.5 mg, about 4.9±0.4 mg, about 4.9±0.3 mg, about 4.9±0.2 mg, or about 4.9±0.1 mg (e.g.. about 4.9 mg) of the disintegrant (e.g., croscarmellose sodium).

[0126] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 4.9±2.0 mg, about 4.9±1.5 mg, about 4.9±1.0 mg, about 4.9±0.9 mg, about 4.9±0.8 mg, about 4.9±0.7 mg, about 4.9±0.6 mg. about 4.9±0.5 mg, about 4.9±0.4 mg, about 4.9±0.3 mg, about 4.9±0.2 mg, or about 4.9±0.1 mg (e.g.. about 4.9 mg) of the disintegrant (e.g., croscarmellose sodium).

[0127] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 6.5±2.0 mg, about 6.5±1.5 mg, about 6.5±1.0 mg, about 6.5±0.9 mg, about 6.5±0.8 mg, about 6.5±0.7 mg, about 6.5±0.6 mg. about 6.5±0.5 mg, about 6.5±0.4 mg, about 6.5±0.3 mg, about 6.5±0.2 mg, or about 6.5±0.1 mg (e.g., about 6.5 mg) of the disintegrant (e.g., croscarmellose sodium).

[0128] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 6.5±2.0 mg, about 6.5±1.5 mg, about 6.5±1.0 mg, about 6.5±0.9 mg, about 6.5±0.8 mg, about 6.5±0.7 mg, about 6.5±0.6 mg. about 6.5±0.5 mg. about 6.5±0.4 mg, about 6.5±0.3 mg, about 6.5±0.2 mg, or about 6.5±0.1 mg (e g., about 6.5 mg) of the disintegrant (e.g., croscarmellose sodium).

[0129] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 13±5.0 mg, about 13±4.0 mg, about 13±3.0 mg, about 13±2.0 mg, about 13±1.5 mg, about 13±I .O mg, about 13±0.9 mg, about 13±0.8 mg, about 13±0.7 mg, about 13±0.6 mg, about 13±0.5 mg, about 13±0.4 mg, about 13±0.3 mg, about 13±0.2 mg, or about 13±0.1 mg (e.g., about 13 mg) of the disintegrant (e.g., croscarmellose sodium).

[0130] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 13±5.0 mg, about 13±4.0 mg, about 13±3.0 mg, about 13±2.0 mg, about 13±1.5 mg, about 13±1.0 mg, about 13±0.9 mg, about 13±0.8 mg, about 13±0.7 mg, about 13±0.6 mg, about 13±0.5 mg, about 13±0.4 mg, about 13±0.3 mg, about 13±0.2 mg, or about 13±0.1 mg (e.g., about 13 mg) of the disintegrant (e.g., croscarmellose sodium).Glidants

[0131] In some embodiments, the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

[0132] In some embodiments, the glidant comprises silicon dioxide.

[0133] In some embodiments, the glidant comprises colloidal silicon dioxide.

[0134] In some embodiments, the formulation (e.g., tablet) comprises about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w (e.g., about 1.0% w / w) of the glidant (e.g., colloidal silicon dioxide).

[0135] In some embodiments, the formulation (e.g., tablet) comprises about 2.4±1.0 mg, about 2.4±0.9 mg, about 2.4±0.8 mg, about 2.4±0.7 mg. about 2.4±0.6 mg, about 2.4±0.5 mg, about 2.4±0.4 mg, about 2.4±0.3 mg, about 2.4±0.2 mg. or about 2.4±0. 1 mg (e.g.. about 2.4 mg) of the glidant (e.g., colloidal silicon dioxide).

[0136] In some embodiments, the formulation (e.g., tablet) comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg. or about 3.2±0. 1 mg (e.g., about 3.2 mg) of the glidant (e.g., colloidal silicon dioxide).

[0137] In some embodiments, the formulation (e.g., tablet) comprises about 6.4±3.0 mg, about 6.4±2.0 mg, about 6.4±1.0 mg, about 6.4±0.9 mg, about 6.4±0.8 mg, about 6.4±0.7 mg, about 6.4±0.6 mg, about 6.4±0.5 mg, about 6.4±0.4 mg, about 6.4±0.3 mg. about 6.4±0.2 mg, or about 6.4±0.1 mg (e.g., about 6.4 mg) of the glidant (e.g.. colloidal silicon dioxide).

[0138] In some embodiments, the intragranular mixture of the formulation (e g., tablet) comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w (e.g., about 0.5% w / w) of the glidant (e.g.. colloidal silicon dioxide).

[0139] In some embodiments, the extragranular mixture of the formulation (e.g.. tablet) comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0. 1 % w / w (e.g., about 0.5% w / w) of the glidant (e.g., colloidal silicon dioxide).

[0140] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 1.2±0.8 mg, about 1.2±0.7 mg, about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg, about 1.2±0.3 mg, about 1.2±0.2 mg, or about 1.2±0.1 mg (e.g., about 1.2 mg) of the glidant (e.g., colloidal silicon dioxide).

[0141] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 1.2±0.8 mg, about 1.2±0.7 mg, about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg, about 1.2±0.3 mg, about 1.2±0.2 mg. or about 1.2±0. 1 mg (e.g.. about 1.2 mg) of the glidant (e.g., colloidal silicon dioxide).

[0142] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about 1.6±0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg, or about 1.6±0. 1 mg (e.g., about 1.6 mg) of the glidant (e.g., colloidal silicon dioxide).

[0143] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about 1.6±0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg, or about 1.6±0.1 mg (e.g., about 1.6 mg) of the glidant (e.g., colloidal silicon dioxide).

[0144] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg. about 3.2±0.3 mg. about 3.2±0.2 mg, or about 3.2±0.1 mg (e.g., about 3.2 mg) of the glidant (e.g., colloidal silicon dioxide).

[0145] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg. about 3.2±0.3 mg. about 3.2±0.2 mg, or about 3.2±0.1 mg (e.g., about 3.2 mg) of the glidant (e.g., colloidal silicon dioxide).Lubricants

[0146] In some embodiments, the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

[0147] In some embodiments, the lubricant comprises a magnesium salt.

[0148] In some embodiments, the lubricant comprises magnesium stearate.

[0149] In some embodiments, the formulation (e.g.. tablet) comprises about 1.0±0.5% w / w, about 1 ,0±0.4% w / w, about 1 ,0±0.3% w / w, about 1 ,0±0.2% w / w, or about 1 ,0±0. 1 % w / w (e.g., about 1.0% w / w) of the lubricant (e.g., magnesium stearate).

[0150] In some embodiments, the formulation (e.g.. tablet) comprises about 2.4±1.0 mg, about 2.4±0.9 mg, about 2.4±0.8 mg, about 2.4±0.7 mg. about 2.4±0.6 mg, about 2.4±0.5 mg, about 2.4±0.4 mg, about 2.4±0.3 mg, about 2.4±0.2 mg, or about 2.4±0.1 mg (e.g., about 2.4 mg) of the lubricant (e.g., magnesium stearate).

[0151] In some embodiments, the formulation (e.g., tablet) comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg. about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg. or about 3.2±0. 1 mg (e.g.. about 3.2 mg) of the lubricant (e.g., magnesium stearate).

[0152] In some embodiments, the formulation (e.g., tablet) comprises about 6.4±3.0 mg, about 6.4±2.0 mg, about 6.4±1.0 mg, about 6.4±0.9 mg, about 6.4±0.8 mg, about 6.4±0.7 mg, about 6.4±0.6 mg, about 6.4±0.5 mg, about 6.4±0.4 mg. about 6.4±0.3 mg. about 6.4±0.2 mg, or about 6.4±0.1 mg (e.g., about 6.4 mg) of the lubricant (e.g., magnesium stearate).

[0153] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w (e.g., about 0.5% w / w) of the lubricant (e.g., magnesium stearate).

[0154] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w (e.g., about 0.5% w / w) of the lubricant (e.g.. magnesium stearate).

[0155] In some embodiments, the intragranular mixture of the formulation (e.g.. tablet) comprises about 1.2±0.8 mg, about 1.2±0.7 mg, about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg, about 1.2±0.3 mg, about 1.2±0.2 mg, or about 1.2±0.1 mg (e.g., about 1.2 mg) of the lubricant (e.g., magnesium stearate).

[0156] In some embodiments, the extragranular mixture of the formulation (e.g.. tablet) comprises about 1.2±0.8 mg, about 1.2±0.7 mg, about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg, about 1.2±0.3 mg, about 1.2±0.2 mg, or about 1.2±0.1 mg (e.g., about 1.2 mg) of the lubricant (e.g., magnesium stearate).

[0157] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about 1.6±0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg, or about 1.6±0.1 mg (e.g., about 1.6 mg) of the lubricant (e.g., magnesium stearate).

[0158] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about 1.6±0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg, or about 1.6±0.1 mg (e.g., about 1.6 mg) of the lubricant (e.g., magnesium stearate).

[0159] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg (e.g., about 3.2 mg) of the lubricant (e.g., magnesium stearate).

[0160] In some embodiments, the extragranular mixture of the formulation (e.g., tablet) comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg. about 3.2±0.3 mg. about 3.2±0.2 mg, or about 3.2±0.1 mg (e.g., about 3.2 mg) of the lubricant (e g., magnesium stearate).Binders

[0161] In some embodiments, the binder comprises polyvinylpyrrolidone (e.g.., Kollidon®), copovidone, maize starch (e.g., pregelatinized maize starch, or partially pregelatinized maizestarch), hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, dextrin, magnesium aluminum silicate, sodium alginate, or any combination thereof.

[0162] In some embodiments, the binder comprises maize starch.

[0163] In some embodiments, the binder comprises partially pregelatinized maize starch.

[0164] In some embodiments, the formulation (e.g., tablet) comprises about 31.6+10% w / w, about 31.6+5.0% w / w. about 31.6+4.0% w / w, about 31.6+3.0% w / w, about 31.6+2.0% w / w, about 31.6+1.5% w / w. about 31.6+1.0% w / w, about 31.6+0.9% w / w, about 31.6+0.8% w / w. about 31.6+0.7% w / w, about 31.6+0.6% w / w, about 31.6+0.5% w / w, about 31.6+0.4% w / w, about 31.6+0.3% w / w, about 31.6+0.2% w / w, or about 31.6+0.1% w / w (e.g., about 31.6% w / w) of the binder (e.g., partially pregelatinized maize starch).

[0165] In some embodiments, the formulation (e.g., tablet) comprises about 77±15 mg, about 77+10 mg, about 77+5.0 mg, about 77+4.0 mg, about 77+3.0 mg, about 77±2.0 mg, about 77+1.5 mg, about 77+1.0 mg, about 77±0.9 mg, about 77+0.8 mg, about 77+0.7 mg, about 77+0.6 mg, about 77+0.5 mg, about 77+0.4 mg, about 77+0.3 mg, about 77+0.2 mg. or about 77+0.1 mg (e.g., about 77 mg) of the binder (e.g., partially pregelatinized maize starch).

[0166] In some embodiments, the formulation (e.g.. tablet) comprises about 103+20 mg. about 103±15 mg, about 103+10 mg, about 103±5.0 mg, about 103+4.0 mg, about 103+3.0 mg, about 103±2.0 mg, about 103+1.5 mg, about 103±1.0 mg, about 103+0.9 mg, about 103±0.8 mg, about 103±0.7 mg. about 103±0.6 mg, about 103±0.5 mg, about 103±0.4 mg, about 103±0.3 mg, about 103+0.2 mg, or about 103+0. 1 mg (e.g., about 103 mg) of the binder (e.g., partially pregelatinized maize starch).

[0167] In some embodiments, the formulation (e.g., tablet) comprises about 206+40 mg, about 206+30 mg, about 206+20 mg, about 206+15 mg, about 206+10 mg, about 206+5.0 mg, about 206±4.0 mg, about 206±3.0 mg, about 206±2.0 mg, about 206+1.5 mg, about 206±1.0 mg, about 206+0.9 mg, about 206±0.8 mg, about 206+0.7 mg, about 206±0.6 mg, about 206+0.5 mg, about 206+0.4 mg, about 206+0.3 mg, about 206±0.2 mg, or about 206+0.1 mg (e.g., about 206 mg) of the binder (e.g., partially pregelatinized maize starch).

[0168] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 31.6+10% w / w, about 31.6+5.0% w / w. about 31.6+4.0% w / w, about 31.6+3.0% w / w, about 31.6+2.0% w / w, about 31.6+1.5% w / w, about 31.6+1.0% w / w, about 31.6+0.9% w / w, about 31.6+0.8% w / w, about 31.6+0.7% w / w, about 31.6+0.6% w / w, about 31.6+0.5% w / w, about 31.6+0.4% w / w, about 31.6+0.3% w / w, about 31.6+0.2% w / w, or about 31.6+0.1% w / w (e.g., about 31.6% w / w) of the binder (e.g., partially pregelatinized maize starch).

[0169] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 77±15 mg, about 77±10 mg, about 77±5.0 mg, about 77±4.0 mg, about 77±3.0 mg, about 77±2.0 mg, about 77±1.5 mg, about 77±1.0 mg, about 77±0.9 mg, about 77±0.8 mg, about 77±0.7 mg, about 77±0.6 mg, about 77±0.5 mg, about 77±0.4 mg, about 77±0.3 mg, about 77±0.2 mg, or about 77±0.1 mg (e.g., about 77 mg) of the binder (e.g., partially pregelatinized maize starch).

[0170] In some embodiments, the intragranular mixture of the formulation (e.g.. tablet) comprises about 103±20 mg, about 103±15 mg, about 103±10 mg, about 103±5.0 mg, about 103±4.0 mg, about 103±3.0 mg, about 103±2.0 mg, about 103±1.5 mg, about 103±1.0 mg, about 103±0.9 mg. about 103±0.8 mg, about 103±0.7 mg, about 103±0.6 mg, about 103±0.5 mg, about 103±0.4 mg. about 103±0.3 mg. about 103±0.2 mg. or about 103±0. 1 mg (e.g., about 103 mg) of the binder (e.g., partially pregelatinized maize starch).

[0171] In some embodiments, the intragranular mixture of the formulation (e.g., tablet) comprises about 206±40 mg, about 206±30 mg, about 206±20 mg, about 206±15 mg, about 206±10 mg, about 206±5.0 mg, about 206±4.0 mg, about 206±3.0 mg, about 206±2.0 mg, about 206±1.5 mg. about 206±1.0 mg, about 206±0.9 mg, about 206±0.8 mg. about 206±0.7 mg, about 206±0.6 mg, about 206±0.5 mg, about 206±0.4 mg, about 206±0.3 mg, about 206±0.2 mg, or about 206±0.1 mg (e.g., about 206 mg) of the binder (e.g., partially pregelatinized maize starch).Exemplary Embodiments

[0172] In some embodiments, the formulation (e.g., tablet) comprises one or more of the ingredients described in Table Bl.Table Bl

[0173] In some embodiments, the formulation (e.g., tablet) comprises one or more of the ingredients described in Table B2.Table B2

[0174] In some embodiments, the formulation (e.g., tablet) comprises one or more of the ingredients described in Table B3.Table B3

[0175] In some embodiments, the formulation (e.g., tablet) comprises one or more of the ingredients described in Table B4.Table B4

[0176] In some embodiments, the formulation (e.g., tablet) is selected from the formulations described in Table 2.Processes of Preparing Formulations

[0177] In some aspects, the present disclosure provides a method for preparing a formulation disclosed herein.

[0178] In some embodiments, the formulation is a capsule.

[0179] In some embodiments, the method comprises: (i) preparing a mixture of Compound No. 1 (Compound No. 1 A and / or Compound No. IB), a filler (e g., microcrystalline cellulose), a disintegrant (e.g., croscarmellose sodium), and a glidant (e.g., colloidal silicon dioxide).

[0180] In some embodiments, the method further comprises sieving and / or blending the mixture.

[0181] In some embodiments, the method further comprises: (ii) adding a lubricant (e.g., magnesium stearate) to the mixture.

[0182] In some embodiments, the method further comprises: (iii) encapsulating and / or packing the mixture, thereby forming the capsule.

[0183] In some embodiments, the method comprises one or more steps as described in FIG. 1.

[0184] In some embodiments, the formulation is a tablet.

[0185] In some embodiments, the method comprises: (i) preparing an intragranular mixture comprising Compound No. 1 (Compound No. 1A and / or Compound No. IB), a filler (e.g., microcrystalline cellulose), a disintegrant (e.g., croscarmellose sodium), and a glidant (e.g., colloidal silicon dioxide).

[0186] In some embodiments, the method further comprises: (ii) adding a lubricant (e.g., magnesium stearate) to the intragranular mixture.

[0187] In some embodiments, the method further comprises: (iii) adding an extragranular disintegrant (e.g., croscarmellose sodium), and an extragranular glidant (e.g., colloidal silicon dioxide) to the mixture.

[0188] In some embodiments, the method further comprises: (iv) adding an extra granular lubricant (e.g., magnesium stearate) to the mixture, thereby forming the tablet.

[0189] In some embodiments, the method comprises one or more steps as described in FIGS. 2A-2C.

[0190] The formulations containing compounds of the present disclosure may be manufactured in a manner that is generally known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes. Pharmaceutical compositions may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers comprising excipients and / or auxiliaries that facilitate processing of the active compounds into preparations that can be used pharmaceutically . In some embodiments, pharmaceutical compositions may be formulated by a method comprising evaporation or by spray drying.Methods of Use

[0191] In some aspects, the present disclosure provides a method of inhibiting an oncogenic variant of an ErbB receptor in a subject, comprising administering to the subject a formulation disclosed herein.

[0192] In some aspects, the present disclosure provides a formulation disclosed herein for use in inhibiting an oncogenic variant of an ErbB receptor in a subject.

[0193] In some aspects, the present disclosure provides a method of treating or preventing cancer in a subject, comprising administering to the subject a formulation disclosed herein.

[0194] In some aspects, the present disclosure provides a formulation disclosed herein for use in treating or preventing cancer in a subject.

[0195] In some embodiments, the subject is a mammal.

[0196] In some embodiments, the subject is a human.

[0197] In some embodiments, the subject is a mouse.

[0198] In some embodiments, cancer is a solid tumor.

[0199] In some embodiments, the cancer is a bladder cancer, a breast cancer, a cervical cancer, a colorectal cancer, an endometrial cancer, a gastric cancer, a glioblastoma (GBM), ahead and neck cancer, a lung cancer, a non-small cell lung cancer (NSCLC), or any subtype thereof.

[0200] In some embodiments, the cancer is glioblastoma (GBM) or any subtype thereof. In some embodiments, the cancer is glioblastoma (GBM).

[0201] In some embodiments, the cancer is glioblastoma (GBM) and the cancer is characterized by overexpression of EGFR.

[0202] In some embodiments, the cancer is methylated glioblastoma. In some embodiments, the cancer is unmethylated glioblastoma.

[0203] In some embodiments, the cancer is recurrent glioblastoma.

[0204] In some embodiments, the cancer is relapsed glioblastoma.

[0205] In some embodiments, the cancer is glioblastoma and the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR.

[0206] In some embodiments, the cancer is relapsed glioblastoma and the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR.

[0207] In some embodiments, the cancer is recurrent glioblastoma and the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR.

[0208] In some embodiments, the cancer is non-small cell lung cancer (NSCLC) or any subtype thereof.

[0209] In some embodiments, the cancer is non-small cell lung cancer (NSCLC).

[0210] In some embodiments, the cancer is recurrent non-small cell lung cancer (NSCLC).

[0211] In some embodiments, the cancer is relapsed non-small cell lung cancer (NSCLC).

[0212] In some embodiments, the cancer is NSCLC and the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR.

[0213] In some embodiments, the cancer is recurrent NSCLC and the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR.

[0214] In some embodiments, the cancer is relapsed NSCLC and the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR.

[0215] In some embodiments, the cancer is advanced or metastatic NSCLC .

[0216] In some embodiments, the cancer is advanced or metastatic NSCLC and the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR.

[0217] In some embodiments, the cancer is NSCLC. wherein the cancer has metastasized to the central nervous system (CNS).

[0218] In some embodiments, the cancer is advanced or metastatic NSCLC, wherein the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR, and wherein the cancer has metastasized to the central nervous system (CNS).

[0219] In some embodiments, the cancer is advanced or metastatic NSCLC, wherein the cancer, or a tumor or cell thereof, expresses at least one oncogenic variant of EGFR, and wherein the cancer has not metastasized to the central nervous system (CNS).

[0220] In some embodiments, the cancer is NSCLC, wherein the cancer has not metastasized to cerebrospinal fluid (CSF).

[0221] In some embodiments, the cancer is NSCLC. wherein the cancer has metastasized to cerebrospinal fluid (CSF).

[0222] In some embodiments, the cancer is glioblastoma, wherein the cancer has not metastasized to cerebrospinal fluid (CSF).

[0223] In some embodiments, the cancer is glioblastoma, wherein the cancer has metastasized to cerebrospinal fluid (CSF).

[0224] In some embodiments, the cancer is NSCLC, wherein the cancer has not metastasized to the brain.

[0225] In some embodiments, the cancer is NSCLC, wherein the cancer has metastasized to the brain.

[0226] In some embodiments, the subject has a central nervous system (CNS) disease.

[0227] In some embodiments, the subject does not have any CNS disease.

[0228] In some embodiments, the subject has a leptomeningeal disease.

[0229] In some embodiments, the subject does not have any leptomeningeal disease.

[0230] In some embodiments, the cancer is NSCLC and the subject has leptomeningeal disease.

[0231] In some embodiments, the cancer is glioblastoma and the subject has leptomeningeal disease.

[0232] In some embodiments, the cancer, or a tumor or a cell thereof, expresses an oncogenic variant of an ErbB receptor.

[0233] It is understood that an oncogenic variant of an ErbB receptor is an ErbB receptor protein that comprises at least one oncogenic mutation and that is produced as the result of the expression of a gene encoding the ErbB receptor that comprises at least one oncogenic mutation.

[0234] As would be appreciated by the skilled artisan, in the context of a gene (e.g. a gene encoding an ErbB receptor), an oncogenic mutation can include, but is not limited to a mutation that results in the substitution of one amino acid for another at a specific position within an ErbB receptor, a mutation that results in an insertion of one or more amino acids between two positions within an ErbB receptor, a mutation that results in the deletion of one more aminoacids between two positions within an ErbB receptor, and mutation that results in a fusion of an ErbB receptor or portion thereof, with another protein, or portion thereof. As would be appreciated by the skilled artisan, in the context of a gene, an oncogenic mutation can include, but is not limited to, a missense mutation, a nonsynonymous mutation, an insertion of one or more nucleotides, a deletion of one or more nucleotides, an inversion and a deletion-insertion.

[0235] As would be appreciated by the skilled artisan, in the context of a protein (e.g. an ErbB receptor), an oncogenic mutation can include, but is not limited to. the substitution of one amino acid for another at a specific position within an ErbB receptor, an insertion of one or more amino acids between two positions within an ErbB receptor, a deletion of one more amino acids between two positions within an ErbB receptor, and a fusion of an ErbB receptor, or portion thereof, with another protein, or portion thereof.

[0236] In some embodiments, the oncogenic variant of the ErbB receptor comprises an allosteric mutation.

[0237] In some embodiments, the oncogenic variant of an ErbB receptor is an allosteric variant of the ErbB receptor.

[0238] In some embodiments, the ErbB receptor is an epidermal growth factor receptor (EGFR) or a human epidermal growth factor receptor 2 (HER2) receptor.

[0239] In some embodiments, the ErbB receptor is an epidermal growth factor receptor (EGFR).

[0240] In some embodiments, the ErbB receptor is a HER2 receptor.

[0241] In some embodiments, the ErbB receptor is a HER3 receptor.

[0242] In some embodiments, the ErbB receptor is aHER4 receptor.

[0243] In some embodiments, the cancer, or a tumor or a cell thereof, expresses an oncogenic variant of an epidermal growth factor receptor (EGFR).

[0244] In some embodiments, the oncogenic variant of EGFR is an allosteric variant of EGFR.

[0245] In some embodiments, the oncogenic variant of EGFR comprises an allosteric mutation.

[0246] In some embodiments, the cancer, or a tumor or a cell thereof, expresses an oncogenic variant of a HER2 receptor.

[0247] In some embodiments, the oncogenic variant of the HER2 receptor is an allosteric variant of the HER2 receptor.

[0248] In some embodiments, the oncogenic variant of the HER2 receptor comprises an allosteric mutation.

[0249] In some embodiments, the oncogenic variant of an EGFR comprises an EGFR variant III (EGFR-Viii) mutation.

[0250] In some embodiments, the oncogenic variant of EGFR comprises an EGFR variant II (EGFR-Vii) mutation.

[0251] In some embodiments, the oncogenic variant of EGFR comprises an EGFR variant VI (EGFR-Vvi) mutation.Definitions

[0252] Unless explicitly indicated otherwise, the terms “approximately” and “about” are synonymous. In some embodiments, “approximately” and “about” refer to the recited amount, value, dose, or duration ± 10%, ± 8%, ± 6%. ± 5%, ± 4%. ± 2%, ± 1%, or ± 0.5%. In some embodiments, “approximately” and “about” refer to the listed amount or duration ± 10%, ± 8%, ± 6%, ± 5%, ± 4%, or ± 2%. In some embodiments, “approximately” and “about” refer to the listed amount, value, dose, or duration ± 5%. In some embodiments, “approximately” and “about” refer to the listed amount, value, dose, or duration ± 2%. In some embodiments, “approximately” and “about” refer to the listed amount, value, dose, or duration ± 1%.

[0253] It is to be understood that the compounds of any Formula described herein include the compounds themselves, as well as their salts, and their solvates, if applicable. A salt, for example, can be formed between an anion and a positively charged group (e.g.. amino) on a substituted benzene compound. Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, tri fluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate (e.g., trifluoroacetate).

[0254] It is to be understood that the compounds of the present disclosure, for example, the salts of the compounds, can exist in either hydrated or unhydrated (the anhydrous) form or as solvates with other solvent molecules. Nonlimiting examples of hydrates include monohydrates, dihydrates, etc. Nonlimiting examples of solvates include ethanol solvates, acetone solvates, etc.

[0255] As used herein, the term “solvate” means solvent addition forms that contain either stoichiometric or non-stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in a solid state (e.g., a crystalline solid state), thus forming a solvate. If the solvent is water, the solvate formed is a hydrate; and if the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of oneor more molecules of water with one molecule of the substance in which the water retains its molecular state as H2O.

[0256] It is to be understood that the present disclosure provides methods for the preparation of the formulations described herein. The present disclosure also provides detailed methods for preparation of various formulations of the present disclosure according to the following Examples.

[0257] It is to be understood that, unless otherwise stated, any description of a method of treatment includes use of the compounds to provide such treatment as is described herein, as well as use of the compounds to prepare a medicament to treat such condition. The treatment includes treatment of human or non-human animals including rodents and other disease models.

[0258] It is to be understood that, unless otherwise stated, any description of a method of prevention includes use of the compounds to provide such prevention as is described herein, as well as use of the compounds to prepare a medicament to prevent such condition. The prevention includes prevention in human or non-human animals including rodents and other disease models.

[0259] As used herein, the term “subject” is interchangeable with the term “subject in need thereof’, both of which refer to a subject having a disease or having an increased risk of developing the disease. A “subject” includes a mammal. The mammal can be e.g., a human or appropriate non-human mammal, such as primate, mouse, rat, dog. cat, cow, horse, goat, camel, sheep or a pig. The subject can also be a bird or fowl. In one embodiment, the mammal is a human.

[0260] As used herein, the term “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of a compound of the present disclosure, or a pharmaceutically acceptable salt, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model.

[0261] It is to be understood that a compound of the present disclosure, or a pharmaceutically acceptable salt, can or may also be used to prevent a relevant disease, condition or disorder, or used to identify suitable candidates for such purposes.

[0262] As used herein, the term “preventing,” “prevent,” or “protecting against” describes reducing or eliminating the onset of the symptoms or complications of such disease, condition or disorder.

[0263] As used herein, the term “pharmaceutically acceptable’' refers to those compounds, anions, cations, materials, compositions, carriers, and / or dosage forms which are. within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0264] It is to be understood that the pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0265] As used herein, the term “pharmaceutically acceptable salts” refer to derivatives of the compounds of the present disclosure wherein the parent compound is modified by making acid or base salts thereof. In some embodiments, the pharmaceutically acceptable salt of a compound (e.g., a 0-lactam compound or probenecid described herein) is also a prodrug of the compound. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 2-acetoxybenzoic, 2-hydroxyethane sulfonic, acetic, ascorbic, benzene sulfonic, benzoic, bicarbonic, carbonic, citric, edetic. ethane disulfonic, 1,2-ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methane sulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicylic, stearic, subacetic. succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, toluene sulfonic, and the commonly occurring amine acids, e.g., glycine, alanine, phenylalanine, arginine, etc.

[0266] Other examples of pharmaceutically acceptable salts include hexanoic acid, cyclopentane propionic acid, pyruvic acid, malonic acid. 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid. 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo-[2.2.2]-oct-2-ene-l-carboxylic acid, 3- phenylpropionic acid, trimethylacetic acid, tertiary' butylacetic acid, muconic acid, and the like. The present disclosure also encompasses salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine,diethanolamine, triethanolamine, tromethamine, N-methylglucamine. and the like. In the salt form, it is understood that the ratio of the compound to the cation or anion of the salt can be 1 : 1, or any ratio other than 1: 1, e.g., 3: 1, 2:1, 1:2, or 1 :3.

[0267] It is to be understood that all references to compounds include solvent addition forms (solvates) or cry stal forms (polymorphs) as defined herein, of the same compound.

[0268] It is to be understood that all references to pharmaceutically acceptable salts include solvent addition forms (solvates) or crystal forms (polymorphs) as defined herein, of the same salt.

[0269] The dosage regimen utilizing the compounds is selected in accordance with a variety7of factors including type, species, age, weight, sex and medical condition of the patient; the severity7of the condition to be treated; the route of administration; the renal and hepatic function of the patient; and the particular compound or salt thereof employed. An ordinarily skilled physician or veterinarian can readily determine and prescribe the effective amount of the drug required to prevent, counter, or arrest the progress of the condition.

[0270] All percentages and ratios used herein, unless otherwise indicated, are by weight. Other features and advantages of the present disclosure are apparent from the different examples. The provided examples illustrate different components and methodology useful in practicing the present disclosure. The examples do not limit the claimed disclosure. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present disclosure.

[0271] All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an admission that any is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description and examples below are for purposes of illustration and not limitation of the claims that follow.EXEMPLARY EMBODIMENTS

[0272] Exemplary Embodiment No. 1. A formulation comprising Compound No. 1 :or a pharmaceutically acceptable salt thereof.

[0273] Exemplary Embodiment No. 2. The formulation of Exemplary Embodiment No. 1, comprising Compound No. 1A:(Compound No. 1A) or a pharmaceutically acceptable salt thereof.

[0274] Exemplary Embodiment No. 3. The formulation of Exemplary Embodiment No. 1, comprising Compound No. IB:(Compound No. IB) or a pharmaceutically acceptable salt thereof.

[0275] Exemplary Embodiment No. 4. The formulation of any one of the preceding Exemplary Embodiments, wherein the formulation is a capsule.

[0276] Exemplary Embodiment No. 5. The formulation of any one of the preceding Exemplary Embodiments, further comprising a filler, a disintegrant, a glidant, and a lubricant.

[0277] Exemplary Embodiment No. 6. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 5.6±2.0% w / w, about 5.6+1.5% w / w, about 5.6+1.0% w / w, about 5.6±0.9% w / w, about 5.6+0.8% w / w, about 5.6±0.7% w / w, about 5.6±0.6% w / w. about 5.6±0.5% w / w, about 5.6±0.4% w / w, about 5.6+0.3% w / w, about 5.6+0.2% w / w, or about 5.6+0.1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 5.0+2.0 mg, about 5.0±1.5 mg, about 5.0+1.0 mg, about 5.0±0.9 mg, about 5.0+0.8 mg, about 5.0±0.7 mg, about 5.0±0.6 mg. about 5.0±0.5 mg, about 5.0+0.4 mg, about 5.0+0.3 mg, about 5.0+0.2 mg, or about 5.0+0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 27.8+5.0% w / w, about 27.8+4.0% w / w, about 27.8+3.0% w / w, about 27.8±2.0% w / w, about 27.8+1.5% w / w, about 27.8+1.0% w / w, about 27.8±0.9% w / w, about 27.8+0.8% w / w. about 27.8+0.7% w / w. about 27.8+0.6% w / w. about 27.8+0.5% w / w. about 27.8+0.4% w / w, about 27.8+0.3% w / w, about 27.8+0.2% w / w, or about 27.8+0.1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 25±5.0 mg, about 25±4.0 mg, about 25+3.0 mg. about 25+2.0 mg, about 25+1.5 mg, about 25+1.0 mg, about 25+0.9 mg. about 25+0.8 mg, about 25±0.7 mg. about 25±0.6 mg, about 25+0.5 mg, about 25+0.4 mg, about 25+0.3 mg, about 25+0.2 mg, or about 25±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 40+15% w / w, about 40+10% w / w, about 40+5.0% w / w, about 40+4.0% w / w, about 40±3.0% w / w. about 40+2.0% w / w. about 40+1.5% w / w. about 40+1.0% w / w, about 40+0.9% w / w, about 40+0.8% w / w, about 40+0.7% w / w, about 40±0.6% w / w, about 40+0.5% w / w, about 40+0.4% w / w, about 40+0.3% w / w, about 40+0.2% w / w, or about 40+0. 1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; or about 100+15 mg, about 100+10 mg, about 100+5.0 mg, about 100+4.0 mg, about 100+3.0 mg, about 100+2.0 mg. about 100+1.5 mg. about 100+1.0 mg. about 100+0.9 mg. about 100+0.8 mg, about 100+0.7 mg, about 100+0.6 mg, about 100+0.5 mg, about 100+0.4 mg, about 100+0.3 mg, about 100+0.2 mg, or about 100+0. 1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof .

[0278] Exemplary Embodiment No. 7. The formulation of any one of the preceding Exemplary Embodiments, wherein the filler comprises lactose, mannitol, starch,pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or cellulose.

[0279] Exemplary Embodiment No. 8. The formulation of any one of the preceding Exemplary Embodiments, wherein the filler comprises microcrystalline cellulose.

[0280] Exemplary Embodiment No. 9. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 90.4±15% w / w, about 90.4±10% w / w, about 90.4±5.0% w / w, about 90.4±4.0% w / w, about 90.4±3.0% w / w, about 90.4±2.0% w / w, about 90.4±1.5% w / w, about 90.4±1.0% w / w, about 90.4±0.9% w / w, about 90.4±0.8% w / w, about 90.4±0.7% w / w, about 90.4±0.6% w / w, about 90.4±0.5% w / w, about 90.4±0.4% w / w, about 90.4±0.3% w / w. about 90.4±0.2% w / w, or about 90.4±0.1% w / w of microcrystalline cellulose; about 81.4±15 mg, about 81.4±10 mg, about 81.4±5.0 mg, about 81.4±4.0 mg, about 81.4±3.0 mg, about 81.4±2.0 mg, about 81.4±1.5 mg, about 81.4±1.0 mg, about 81.4±0.9 mg, about 81.4±0.8 mg, about 81.4±0.7 mg, about 81.4±0.6 mg. about 81.4±0.5 mg, about 81.4±0.4 mg. about 81.4±0.3 mg, about 81.4±0.2 mg. or about 81.4±0.1 mg of microcrystalline cellulose; about 68.2±15% w / w, about 68.2±10% w / w, about 68.2±5.0% w / w, about 68.2±4.0% w / w, about 68.2±3.0% w / w, about 68.2±2.0% w / w, about 68.2±1.5% w / w, about 68.2±1.0% w / w, about 68.2±0.9% w / w, about 68.2±0.8% w / w. about 68.2±0.7% w / w. about 68.2±0.6% w / w, about 68.2±0.5% w / w, about 68.2±0.4% w / w, about 68.2±0.3% w / w, about 68.2±0.2% w / w, or about 68.2±0.1% w / w of microcrystalline cellulose; about 61.4±15 mg, about 61.4±10 mg, about 61.4±5.0 mg, about 61.4±4.0 mg, about 61.4±3.0 mg. about 61.4±2.0 mg, about 61.4±1.5 mg, about 61.4±1.0 mg, about 61.4±0.9 mg, about 61.4±0.8 mg, about 61.4±0.7 mg, about 61.4±0.6 mg, about 61.4±0.5 mg, about 61.4±0.4 mg, about 61.4+0.3 mg, about 61.4+0.2 mg, or about 61.4+0.1 mg of microcrystalline cellulose; about 50±15% w / w, about 50±10% w / w, about 50+5.0% w / w, about 50+4.0% w / w, about 50±3.0% w / w. about 50+2.0% w / w. about 50+1.5% w / w. about 50+1.0% w / w, about 50+0.9% w / w, about 50+0.8% w / w, about 50+0.7% w / w, about 50±0.6% w / w, about 50+0.5% w / w, about 50+0.4% w / w, about 50+0.3% w / w, about 50+0.2% w / w, or about 50+0.1% w / w of microcrystalline cellulose; or about 125+15 mg, about 125+10 mg, about 125±5.0 mg, about 125±4.0 mg, about 125±3.0 mg, about 125+2.0 mg, about 125+1.5 mg, about 125+1.0 mg, about 125+0.9 mg,about 125±0.8 mg, about 125±0.7 mg, about 125±0.6 mg. about 125±0.5 mg, about 125±0.4 mg, about 125±0.3 mg, about 125±0.2 mg, or about 125±0.1 mg of microcrystalline cellulose.

[0281] Exemplary Embodiment No. 10. The formulation of any one of the preceding Exemplary Embodiments, wherein the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate. chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

[0282] Exemplary Embodiment No. 11. The formulation of any one of the preceding Exemplary Embodiments, wherein the disintegrant comprises croscarmellose sodium.

[0283] Exemplary Embodiment No. 12. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 3.0±2.0% w / w, about 3.0±1.5% w / w, about 3.0±1.0% w / w, about 3.0±0.9% w / w, about 3.0±0.8% w / w, about 3.0±0.7% w / w, about 3.0±0.6% w / w, about 3.0±0.5% w / w, about 3.0±0.4% w / w, about 3.0±0.3% w / w, about 3.0±0.2% w / w. or about 3.0±0.1% w / w of croscarmellose sodium; about 2.7±2.0 mg, about 2.7±1.5 mg, about 2.7±1.0 mg, about 2.7±0.9 mg, about 2.7±0.8 mg, about 2.7±0.7 mg, about 2.7±0.6 mg, about 2.7±0.5 mg, about 2.7±0.4 mg, about 2.7±0.3 mg, about 2.7±0.2 mg, or about 2.7±0.1 mg of croscarmellose sodium; about 8.0±5.0% w / w, about 8.0±4.0% w / w, about 8.0±3.0% w / w. about 8.0±2.0% w / w, about 8.0±1.5% w / w, about 8.0±1.0% w / w, about 8.0±0.9% w / w, about 8.0±0.8% w / w, about 8.0±0.7% w / w, about 8.0±0.6% w / w, about 8.0±0.5% w / w, about 8.0±0.4% w / w, about 8.0±0.3% w / w, about 8.0±0.2% w / w, or about 8.0±0.1% w / w of croscarmellose sodium; or about 20±5.0 mg, about 20±4.0 mg, about 20±3.0 mg. about 20±2.0 mg, about 20±1.5 mg, about 20±1.0 mg, about 20±0.9 mg, about 20±0.8 mg, about 20±0.7 mg, about 20±0.6 mg, about 20±0.5 mg, about 20±0.4 mg, about 20±0.3 mg, about 20±0.2 mg, or about 20±0.1 mg of croscarmellose sodium.

[0284] Exemplary Embodiment No. 13. The formulation of any one of the preceding Exemplary Embodiments, wherein the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

[0285] Exemplary Embodiment No. 14. The formulation of any one of the preceding Exemplary Embodiments, wherein the glidant comprises colloidal silicon dioxide.

[0286] Exemplary Embodiment No. 15. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w of colloidal silicon dioxide; about 0.5±0.3 mg, about 0.5±0.2 mg, or about 0.5±0.1 mg of colloidal silicon dioxide; about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w of colloidal silicon dioxide; or about 2.5±1.0 mg, about 2.5±0.9 mg, about 2.5±0.8 mg, about 2.5±0.7 mg, about 2.5±0.6 mg, about 2.5±0.5 mg, about 2.5±0.4 mg, about 2.5±0.3 mg, about 2.5±0.2 mg, or about 2.5±0.1 mg of colloidal silicon dioxide.

[0287] Exemplary Embodiment No. 16. The formulation of any one of the preceding Exemplary Embodiments, wherein the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

[0288] Exemplary Embodiment No. 17. The formulation of any one of the preceding Exemplary Embodiments, wherein the lubricant comprises magnesium stearate.

[0289] Exemplary Embodiment No. 18. The formulation of any one of the preceding Exemplary7Embodiments, comprising: about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0. 1% w / w of magnesium stearate; about 0.5±0.3 mg, about 0.5±0.2 mg, or about 0.5±0.1 mg of magnesium stearate; about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w of magnesium stearate; or about 2.5±1.0 mg, about 2.5±0.9 mg, about 2.5±0.8 mg. about 2.5±0.7 mg, about 2.5±0.6 mg, about 2.5±0.5 mg, about 2.5±0.4 mg, about 2.5±0.3 mg, about 2.5±0.2 mg, or about 2.5±0.1 mg of the lubricant (e.g., magnesium stearate).

[0290] Exemplary Embodiment No. 19. The formulation of any one of the preceding Exemplary Embodiments, comprising one or more of the ingredients described in Table Al- A6.

[0291] Exemplary Embodiment No. 20. The formulation of any one of the preceding Exemplary' Embodiments, being selected from the formulations described in Table 1.

[0292] Exemplary Embodiment No. 21. The formulation of any one of the preceding Exemplary Embodiments, wherein the formulation is a tablet.

[0293] Exemplary Embodiment No. 22. The formulation of any one of the preceding Exemplary Embodiments, comprising an intragranular mixture and an extragranular mixture.

[0294] Exemplary Embodiment No. 23. The formulation of any one of the preceding Exemplary Embodiments, further comprising a filler, a disintegrant, a glidant, a lubricant, and a binder.

[0295] Exemplary Embodiment No. 24. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 30.8+10% w / w, about 30.8+5.0% w / w, about 30.8±4.0% w / w, about 30.8±3.0% w / w, about 30.8+2.0% w / w, about 30.8+1.5% w / w, about 30.8+1.0% w / w, about 30.8+0.9% w / w, about 30.8±0.8% w / w, about 30.8±0.7% w / w, about 30.8±0.6% w / w, about 30.8±0.5% w / w, about 30.8±0.4% w / w, about 30.8±0.3% w / w, about 30.8±0.2% w / w. or about 30.8+0.1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 75+15 mg, about 75+10 mg, about 75+5.0 mg, about 75±4.0 mg, about 75+3.0 mg, about 75+2.0 mg, about 75+1.5 mg, about 75+1.0 mg, about 75±0.9 mg, about 75+0.8 mg, about 75±0.7 mg, about 75±0.6 mg. about 75+0.5 mg, about 75±0.4 mg, about 75±0.3 mg, about 75+0.2 mg, or about 75+0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 100±15 mg, about 100+10 mg, about 100+5.0 mg, about 100+4.0 mg, about 100±3.0 mg, about 100±2.0 mg, about 100+1.5 mg, about 100±1.0 mg, about 100±0.9 mg. about 100±0.8 mg. about 100+0.7 mg. about 100+0.6 mg. about 100+0.5 mg, about 100+0.4 mg, about 100+0.3 mg, about 100±0.2 mg, or about 100+0. 1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 200+40 mg, about 200+30 mg, about 200+20 mg, about 200+15 mg, about 200±10 mg, about 200+5.0 mg, about 200±4.0 mg, about 200±3.0 mg, about 200±2.0 mg, about 200+1.5 mg, about 200+1.0 mg, about 200+0.9 mg, about 200+0.8 mg, about 200+0.7 mg, about 200+0.6 mg, about 200+0.5 mg, about 200+0.4 mg, about 200+0.3 mg, about 200+0.2 mg, or about 200+0. 1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 30.8+10% w / w, about 30.8+5.0% w / w, about 30.8+4.0% w / w, about 30.8+3.0% w / w, about 30.8+2.0% w / w, about 30.8+1.5% w / w, about 30.8+1.0% w / w, about 30.8+0.9% w / w, about 30.8+0.8% w / w, about 30.8+0.7% w / w, about 30.8+0.6% w / w, about 30.8+0.5% w / w, about 30.8+0.4% w / w, about 30.8+0.3% w / w, about 30.8+0.2% w / w, or about30.8+0. 1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof;about 75±15 mg, about 75±10 mg, about 75±5.0 mg, about 75±4.0 mg, about 75±3.0 mg, about 75±2.0 mg, about 75±1.5 mg. about 75±1.0 mg, about 75±0.9 mg, about 75±0.8 mg, about 75±0.7 mg, about 75±0.6 mg, about 75±0.5 mg, about 75±0.4 mg, about 75±0.3 mg, about 75±0.2 mg, or about 75±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 100±15 mg, about 100±10 mg, about 100±5.0 mg, about 100±4.0 mg, about 100±3.0 mg, about 100±2.0 mg. about 100±1.5 mg. about 100±1.0 mg. about 100±0.9 mg. about 100±0.8 mg, about 100±0.7 mg, about 100±0.6 mg, about 100±0.5 mg, about 100±0.4 mg, about 100±0.3 mg, about 100±0.2 mg, or about 100±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; or about 200±40 mg, about 200±30 mg, about 200±20 mg. about 200±15 mg, about 200±10 mg, about 200±5.0 mg, about 200±4.0 mg, about 200±3.0 mg, about 200±2.0 mg, about 200±1.5 mg, about 200±1.0 mg, about 200±0.9 mg, about 200±0.8 mg, about 200±0.7 mg, about 200±0.6 mg, about 200±0.5 mg, about 200±0.4 mg, about 200±0.3 mg, about 200±0.2 mg, or about 200±0. 1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof.

[0296] Exemplary Embodiment No. 25. The formulation of any one of the preceding Exemplary7Embodiments, wherein the fdler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or cellulose.

[0297] Exemplary Embodiment No. 26. The formulation of any one of the preceding Exemplary Embodiments, wherein the fdler comprises microcrystalline cellulose.

[0298] Exemplary Embodiment No. 27. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 31 ,6±10% w / w, about 31.6±5.0% w / w, about 31.6±4.0% w / w, about 31.6±3.0% w / w, about 31.6±2.0% w / w, about 31.6±1.5% w / w, about 31.6±1.0% w / w, about 31.6±0.9% w / w, about 31.6±0.8% w / w, about 31.6±0.7% w / w, about 31.6±0.6% w / w, about 31.6±0.5% w / w, about 31.6±0.4% w / w. about 31.6±0.3% w / w. about 31.6±0.2% w / w. or about 31.6±0.1% w / w of microcrystalline cellulose; about 77±15 mg, about 77±10 mg, about 77±5.0 mg, about 77±4.0 mg, about 77±3.0 mg, about 77±2.0 mg, about 77±1.5 mg, about 77±1.0 mg, about 77±0.9 mg, about 77±0.8 mg, about 77±0.7 mg, about 77±0.6 mg. about 77±0.5 mg, about 77±0.4 mg, about 77±0.3 mg, about 77±0.2 mg, or about 77±0.1 mg of microcrystalline cellulose;about 103+20 mg, about 103+15 mg, about 103+10 mg, about 103+5.0 mg, about 103±4.0 mg, about 103±3.0 mg, about 103±2.0 mg. about 103±1.5 mg. about 103±1.0 mg. about 103±0.9 mg, about 103+0.8 mg, about 103+0.7 mg, about 103+0.6 mg, about 103+0.5 mg, about 103+0.4 mg, about 103+0.3 mg, about 103+0.2 mg, or about 103+0. 1 mg of microcrystalline cellulose; or about 206+40 mg, about 206+30 mg, about 206+20 mg. about 206+15 mg, about 206+10 mg, about 206+5.0 mg, about 206+4.0 mg, about 206+3.0 mg, about 206+2.0 mg, about 206+1.5 mg, about 206+1.0 mg, about 206+0.9 mg, about 206+0.8 mg, about 206+0.7 mg, about 206+0.6 mg, about 206+0.5 mg, about 206+0.4 mg, about 206+0.3 mg, about 206+0.2 mg, or about 206+0.1 mg of microcrystalline cellulose.

[0299] Exemplary Embodiment No. 28. The formulation of any one of the preceding Exemplary Embodiments, wherein the intragranular mixture comprises: about 31.6+10% w / w, about 31.6+5.0% w / w, about 31.6+4.0% w / w, about 31.6+3.0% w / w, about 31.6+2.0% w / w, about 31.6+1.5% w / w, about 31.6+1.0% w / w, about 31.6+0.9% w / w, about 31.6+0.8% w / w, about 31.6+0.7% w / w, about 31.6+0.6% w / w, about 31.6+0.5% w / w. about 31.6+0.4% w / w. about 31.6+0.3% w / w. about 31.6+0.2% w / w. or about 31.6+0.1% w / w of microcrystalline cellulose; about 77+15 mg, about 77+10 mg, about 77+5.0 mg, about 77+4.0 mg, about 77+3.0 mg, about 77+2.0 mg, about 77+1.5 mg. about 77+1.0 mg, about 77+0.9 mg, about 77+0.8 mg, about 77+0.7 mg, about 77+0.6 mg. about 77+0.5 mg, about 77+0.4 mg. about 77+0.3 mg, about 77+0.2 mg, or about 77+0.1 mg of microcrystalline cellulose; about 103+20 mg, about 103+15 mg, about 103+10 mg, about 103+5.0 mg, about 103+4.0 mg, about 103+3.0 mg, about 103+2.0 mg, about 103+1.5 mg, about 103+1.0 mg, about 103+0.9 mg. about 103+0.8 mg. about 103+0.7 mg. about 103+0.6 mg, about 103+0.5 mg, about 103+0.4 mg, about 103+0.3 mg, about 103+0.2 mg, or about 103+0. 1 mg of microcrystalline cellulose; or about 206+40 mg, about 206+30 mg, about 206+20 mg, about 206+15 mg, about 206+10 mg, about 206+5.0 mg, about 206+4.0 mg, about 206+3.0 mg, about 206+2.0 mg, about 206+1.5 mg. about 206+1.0 mg. about 206+0.9 mg. about 206+0.8 mg, about 206+0.7 mg, about 206+0.6 mg, about 206+0.5 mg, about 206+0.4 mg, about 206+0.3 mg, about 206+0.2 mg, or about 206+0.1 mg of microcrystalline cellulose.

[0300] Exemplary Embodiment No. 29. The formulation of any one of the preceding Exemplary Embodiments, wherein the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate, chitosan hydrochloride, methylcellulose, calciumcarboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

[0301] Exemplary Embodiment No. 30. The formulation of any one of the preceding Exemplary Embodiments, wherein the disintegrant comprises croscarmellose sodium.

[0302] Exemplary Embodiment No. 31. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 4.0±2.0% w / w, about 4.0+1.5% w / w, about 4.0+1.0% w / w. about 4.0+0.9% w / w, about 4.0±0.8% w / w, about 4.0±0.7% w / w, about 4.0±0.6% w / w, about 4.0±0.5% w / w, about 4.0±0.4% w / w, about 4.0+0.3% w / w, about 4.0+0.2% w / w, or about 4.0±0.1% w / w of croscarmellose sodium; about 9.6+4.0 mg, about 9.6±3.0 mg, about 9.6±2.0 mg. about 9.6+1.5 mg, about 9.6+1.0 mg, about 9.6+0.9 mg, about 9.6±0.8 mg, about 9.6±0.7 mg, about 9.6+0.6 mg, about 9.6+0.5 mg, about 9.6+0.4 mg, about 9.6±0.3 mg, about 9.6±0.2 mg, or about 9.6+0. 1 mg of croscarmellose sodium; about 13+5.0 mg, about 13+4.0 mg, about 13±3.0 mg. about 13+2.0 mg, about 13±1.5 mg, about 13+1.0 mg, about 13+0.9 mg. about 13+0.8 mg, about 13+0.7 mg. about 13±0.6 mg, about 13+0.5 mg, about 13+0.4 mg, about 13+0.3 mg, about 13+0.2 mg, or about 13+0.1 mg of croscarmellose sodium; or about 26±10 mg, about 26±5.0 mg, about 26±4.0 mg, about 26+3.0 mg, about 26±2.0 mg, about 26+1.5 mg, about 26+1.0 mg. about 26+0.9 mg, about 26±0.8 mg. about 26±0.7 mg, about 26+0.6 mg, about 26+0.5 mg, about 26+0.4 mg, about 26+0.3 mg, about 26+0.2 mg, or about 26+0.1 mg of croscarmellose sodium.

[0303] Exemplary Embodiment No. 32. The formulation of any one of the preceding Exemplary Embodiments, wherein: the intragranular mixture comprises about 2.0+1.0% w / w, about 2.0±0.9% w / w, about 2.0+0.8% w / w, about 2.0±0.7% w / w, about 2.0+0.6% w / w, about 2.0±0.5% w / w, about 2.0+0.4% w / w, about 2.0±0.3% w / w, about 2.0+0.2% w / w, or about 2.0+0. 1 % w / w of croscarmellose sodium; the extragranular mixture comprises about 2.0+1.0% w / w, about 2.0±0.9% w / w, about 2.0+0.8% w / w, about 2.0+0.7% w / w, about 2.0+0.6% w / w, about 2.0±0.5% w / w, about 2.0+0.4% w / w, about 2.0±0.3% w / w, about 2.0+0.2% w / w, or about 2.0±0.1% w / w of croscarmellose sodium; the intragranular mixture comprises about 4.9=2.0 mg, about 4.9+ 1 .5 mg. about4.9+1.0 mg, about 4.9+0.9 mg, about 4.9+0.8 mg, about 4.9+0.7 mg, about 4.9+0.6 mg, about4.9±0.5 mg, about 4.9±0.4 mg, about 4.9±0.3 mg, about 4.9±0.2 mg, or about 4.9±0.1 mg of croscarmellose sodium; the extragranular mixture comprises about 4.9±2.0 mg, about 4.9±1.5 mg, about 4.9±1.0 mg, about 4.9±0.9 mg, about 4.9±0.8 mg, about 4.9±0.7 mg, about 4.9±0.6 mg, about 4.9±0.5 mg, about 4.9±0.4 mg, about 4.9±0.3 mg, about 4.9±0.2 mg, or about 4.9±0.1 mg of croscarmellose sodium; the intragranular mixture comprises about 6.5±2.0 mg, about 6.5±1.5 mg. about 6.5±1.0 mg, about 6.5±0.9 mg, about 6.5±0.8 mg, about 6.5±0.7 mg, about 6.5±0.6 mg, about 6.5±0.5 mg, about 6.5±0.4 mg, about 6.5±0.3 mg, about 6.5±0.2 mg, or about 6.5±0.1 mg of croscarmellose sodium; the extragranular mixture comprises about 6.5±2.0 mg, about 6.5±1.5 mg, about 6.5±1.0 mg, about 6.5±0.9 mg, about 6.5±0.8 mg, about 6.5±0.7 mg, about 6.5±0.6 mg, about 6.5±0.5 mg, about 6.5±0.4 mg, about 6.5±0.3 mg, about 6.5±0.2 mg, or about 6.5±0. 1 mg of croscarmellose sodium; the intragranular mixture comprises about 13±5.0 mg, about 13±4.0 mg, about 13±3.0 mg, about 13±2.0 mg, about 13±1.5 mg. about 13±1.0 mg, about 13±0.9 mg. about 13±0.8 mg, about 13±0.7 mg, about 13±0.6 mg, about 13±0.5 mg, about 13±0.4 mg, about 13±0.3 mg, about 13±0.2 mg, or about 13±0.1 mg of croscarmellose sodium; and / or the extragranular mixture comprises about 13±5.0 mg, about 13±4.0 mg, about 13±3.0 mg, about 13±2.0 mg, about 13±1.5 mg. about 13±1.0 mg, about 13±0.9 mg. about 13±0.8 mg, about 13±0.7 mg, about 13±0.6 mg, about 13±0.5 mg, about 13±0.4 mg, about 13±0.3 mg, about 13±0.2 mg, or about 13±0.1 of croscarmellose sodium.

[0304] Exemplary Embodiment No. 33. The formulation of any one of the preceding Exemplary Embodiments, wherein the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

[0305] Exemplary Embodiment No. 34. The formulation of any one of the preceding Exemplary Embodiments, wherein the glidant comprises colloidal silicon dioxide.

[0306] Exemplary Embodiment No. 35. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w of colloidal silicon dioxide;about 2.4±1.0 mg, about 2.4±0.9 mg, about 2.4±0.8 mg, about 2.4±0.7 mg, about 2.4±0.6 mg, about 2.4±0.5 mg, about 2.4±0.4 mg. about 2.4±0.3 mg, about 2.4±0.2 mg, or about 2.4±0.1 mg of colloidal silicon dioxide; about 3.2+1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg of colloidal silicon dioxide; or about 6.4±3.0 mg, about 6.4±2.0 mg, about 6.4±1.0 mg. about 6.4±0.9 mg. about 6.4±0.8 mg, about 6.4±0.7 mg, about 6.4±0.6 mg, about 6.4±0.5 mg, about 6.4±0.4 mg, about 6.4±0.3 mg, about 6.4±0.2 mg, or about 6.4±0. 1 mg of colloidal silicon dioxide.

[0307] Exemplary Embodiment No. 36. The formulation of any one of the preceding Exemplary Embodiments, wherein: the intragranular mixture comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w of colloidal silicon dioxide; the extragranular mixture comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w of colloidal silicon dioxide; the intragranular mixture comprises about 1.2±0.8 mg, about 1.2±0.7 mg. about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg, about 1.2±0.3 mg, about 1.2±0.2 mg, or about 1.2±0.1 mg of colloidal silicon dioxide; the extragranular mixture comprises about 1.2±0.8 mg, about 1.2±0.7 mg, about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg. about 1.2±0.3 mg, about 1.2±0.2 mg, or about 1.2±0.1 mg of colloidal silicon dioxide; the intragranular mixture comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about 1.6±0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg, or about 1 ,6±0.1 mg of colloidal silicon dioxide; the extragranular mixture comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about 1.6+0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg, or about 1 ,6±0.1 mg of colloidal silicon dioxide; the intragranular mixture comprises about 3.2±1.0 mg, about 3.2±0.9 mg. about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg. about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg of colloidal silicon dioxide; and / or the extragranular mixture comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg of colloidal silicon dioxide.

[0308] Exemplary Embodiment No. 37. The formulation of any one of the preceding Exemplary Embodiments, wherein the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

[0309] Exemplary Embodiment No. 38. The formulation of any one of the preceding Exemplary Embodiments, wherein the lubricant comprises magnesium stearate.

[0310] Exemplary Embodiment No. 39. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0. 1% w / w of magnesium stearate; about 2.4±1.0 mg, about 2.4±0.9 mg, about 2.4±0.8 mg. about 2.4±0.7 mg, about 2.4±0.6 mg, about 2.4±0.5 mg, about 2.4±0.4 mg, about 2.4±0.3 mg, about 2.4±0.2 mg, or about 2.4±0.1 mg of magnesium stearate; about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg of magnesium stearate; or about 6.4±3.0 mg, about 6.4±2.0 mg, about 6.4±1.0 mg, about 6.4±0.9 mg, about 6.4±0.8 mg, about 6.4±0.7 mg, about 6.4±0.6 mg, about 6.4±0.5 mg, about 6.4±0.4 mg, about 6.4±0.3 mg, about 6.4±0.2 mg, or about 6.4±0. 1 mg of magnesium stearate.

[0311] Exemplary Embodiment No. 40. The formulation of any one of the preceding Exemplary Embodiments, wherein: the intragranular mixture comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w of magnesium stearate; the extragranular mixture comprises about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w of magnesium stearate; the intragranular mixture comprises about 1.2±0.8 mg, about 1.2±0.7 mg, about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg, about 1.2±0.3 mg, about 1.2±0.2 mg, or about 1.2±0.1 mg of magnesium stearate; the extragranular mixture comprises about 1.2±0.8 mg, about 1.2±0.7 mg, about 1.2±0.6 mg, about 1.2±0.5 mg, about 1.2±0.4 mg, about 1.2±0.3 mg, about 1.2±0.2 mg, or about 1.2±0.1 mg of magnesium stearate; the intragranular mixture comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about1.6±0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg. or about 1.6±0.1 mg of magnesium stearate;the extragranular mixture comprises about 1.6±0.6 mg, about 1.6±0.5 mg, about 1.6±0.4 mg, about 1.6±0.3 mg, about 1.6±0.2 mg. or about 1.6±0.1 mg of magnesium stearate: the intragranular mixture comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg of magnesium stearate; and / or the extragranular mixture comprises about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg.

[0312] Exemplary Embodiment No. 41. The formulation of any one of the preceding Exemplary Embodiments, wherein the binder comprises polyvinylpyrrolidone, copovidone, maize starch, hydroxypropyl methylcellulose, hydroxy ethyl cellulose, hydroxypropyl cellulose, dextrin, magnesium aluminum silicate, or sodium alginate.

[0313] Exemplary Embodiment No. 42. The formulation of any one of the preceding Exemplary Embodiments, wherein the binder comprises partially pregelatinized maize starch.

[0314] Exemplary Embodiment No. 43. The formulation of any one of the preceding Exemplary Embodiments, comprising: about 31.6±10% w / w, about 31.6±5.0% w / w, about 31.6±4.0% w / w, about 31.6±3.0% w / w, about 31.6±2.0% w / w, about 31.6±1.5% w / w, about 31.6±1.0% w / w, about 31.6±0.9% w / w, about 31.6±0.8% w / w, about 31.6±0.7% w / w. about 31.6±0.6% w / w. about 31.6±0.5% w / w, about 31 ,6±0.4% w / w, about 31 ,6±0.3% w / w, about 31 ,6±0.2% w / w, or about 31.6±0.1% w / w of partially pregelatinized maize starch; about 77±15 mg, about 77±10 mg, about 77±5.0 mg, about 77±4.0 mg, about 77±3.0 mg, about 77±2.0 mg, about 77±1.5 mg. about 77±1.0 mg, about 77±0.9 mg, about 77±0.8 mg, about 77±0.7 mg, about 77±0.6 mg, about 77±0.5 mg, about 77±0.4 mg, about 77±0.3 mg, about 77±0.2 mg, or about 77±0.1 mg of partially pregelatinized maize starch; about 103±20 mg, about 103±15 mg, about 103±10 mg, about 103±5.0 mg, about 103±4.0 mg, about 103±3.0 mg, about 103±2.0 mg, about 103±1.5 mg, about 103±1.0 mg. about 103±0.9 mg. about 103±0.8 mg. about 103±0.7 mg. about 103±0.6 mg, about 103±0.5 mg, about 103±0.4 mg, about 103±0.3 mg, about 103±0.2 mg, or about 103±0. 1 mg of partially pregelatinized maize starch; or about 206±40 mg, about 206±30 mg, about 206±20 mg, about 206±15 mg, about 206±10 mg, about 206±5.0 mg, about 206±4.0 mg, about 206±3.0 mg, about 206±2.0 mg, about 206±1.5 mg, about 206±1.0 mg, about 206±0.9 mg, about 206±0.8 mg, about 206±0.7mg, about 206±0.6 mg, about 206±0.5 mg, about 206±0.4 mg, about 206±0.3 mg, about 206±0.2 mg, or about 206±0.1 mg of partially pregelatinized maize starch.

[0315] Exemplary Embodiment No. 44. The formulation of any one of the preceding Exemplary Embodiments, wherein the intragranular mixture comprises: about 31.6±10% w / w, about 31.6±5.0% w / w, about 31.6±4.0% w / w, about 31.6±3.0% w / w, about 31.6±2.0% w / w, about 31.6±1.5% w / w, about 31.6±1.0% w / w, about 31.6±0.9% w / w, about 31.6±0.8% w / w. about 31.6±0.7% w / w. about 31.6±0.6% w / w. about 31.6±0.5% w / w, about 31.6±0.4% w / w, about 31.6±0.3% w / w, about 31.6±0.2% w / w, or about 31.6±0.1% w / w of partially pregelatinized maize starch; about 77±15 mg, about 77±10 mg, about 77±5.0 mg, about 77±4.0 mg, about 77±3.0 mg, about 77±2.0 mg, about 77±1.5 mg. about 77±1.0 mg, about 77±0.9 mg, about 77±0.8 mg, about 77±0.7 mg, about 77±0.6 mg, about 77±0.5 mg, about 77±0.4 mg, about 77±0.3 mg, about 77±0.2 mg, or about 77±0.1 mg of partially pregelatinized maize starch; about 103±20 mg, about 103±15 mg, about 103±10 mg, about 103±5.0 mg, about 103±4.0 mg, about 103±3.0 mg, about 103±2.0 mg, about 103±1.5 mg, about 103±1.0 mg. about 103±0.9 mg. about 103±0.8 mg. about 103±0.7 mg. about 103±0.6 mg, about 103±0.5 mg, about 103±0.4 mg, about 103±0.3 mg, about 103±0.2 mg, or about 103±0. 1 mg of partially pregelatinized maize starch; or about 206±40 mg, about 206±30 mg, about 206±20 mg, about 206±15 mg, about 206±10 mg, about 206±5.0 mg, about 206±4.0 mg, about 206±3.0 mg, about 206±2.0 mg, about 206±l .5 mg, about 206±l .0 mg, about 206±0.9 mg, about 206±0.8 mg, about 206±0.7 mg, about 206±0.6 mg, about 206±0.5 mg, about 206±0.4 mg, about 206±0.3 mg, about 206±0.2 mg, or about 206±0.1 mg of partially pregelatinized maize starch.

[0316] Exemplary Embodiment No. 45. The formulation of any one of the preceding Exemplary Embodiments, comprising one or more of the ingredients described in Table Bl- B4.

[0317] Exemplary Embodiment No. 46. The formulation of any one of the preceding Exemplary Embodiments, being selected from the formulations described in Table 2.

[0318] Exemplary Embodiment No. 47. A method for preparing the formulation of any one of the preceding Exemplary Embodiments.

[0319] Exemplary Embodiment No. 48. A method of inhibiting an oncogenic variant of an ErbB receptor in a subject, comprising administering to the subject the formulation of any one of the preceding Exemplary Embodiments.

[0320] Exemplary Embodiment No. 49. The formulation of any one of the preceding Exemplary Embodiments for use in inhibiting an oncogenic variant of an ErbB receptor in a subject.

[0321] Exemplary Embodiment No. 50. A method of treating or preventing cancer in a subject, comprising administering to the subject the formulation of any one of the preceding Exemplary Embodiments.

[0322] Exemplary Embodiment No. 51. The formulation of any one of the preceding Exemplary Embodiments for use in treating or preventing cancer in a subject.

[0323] Exemplary Embodiment No. 52. The method or formulation of any one of the preceding Exemplar}' Embodiments, wherein the subject is a human.

[0324] Exemplary Embodiment No. 53. The method or formulation of any one of the preceding Exemplar}' Embodiments, wherein the subject is a mouse.

[0325] Exemplary Embodiment No. 54. The method or formulation of any one of the preceding Exemplar}' Embodiments, wherein the cancer is a solid tumor.

[0326] Exemplary Embodiment No. 55. The method or formulation of any one of the preceding Exemplar}' Embodiments, wherein the cancer is a bladder cancer, a breast cancer, a cervical cancer, a colorectal cancer, an endometrial cancer, a gastric cancer, a glioblastoma (GBM), a head and neck cancer, a lung cancer, a non-small cell lung cancer (NSCLC), or any subtype thereof.

[0327] Exemplary Embodiment No. 56. The method or formulation of any one of the preceding Exemplar}' Embodiments, wherein the cancer is glioblastoma (GBM) or any subtype thereof.

[0328] Exemplary Embodiment No. 57. The method or formulation of any one of the preceding Exemplar}’ Embodiments, wherein the cancer is glioblastoma (GBM).EXAMPLES

[0329] It is understood that the values described in the examples are approximate and subject to experimental and instrumental variations.Example 1. Exemplary Preparation of Capsules.

[0330] Following the procedures described in FIG. 1, capsules comprising Compound No. 1 were prepared. The compositions of the capsules are summarized in Table 1.Table 1Example 2. Exemplary Preparation of Tablets.

[0331] Following the procedures described in FIG. 2, tablets comprising Compound No. 1 were prepared. The compositions of the tablets are summarized in Table 2.Table 2EQUIVALENTS

[0332] It is to be understood that the invention can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

What is claimed is:1 . A formulation comprising Compound No. 1 :or a pharmaceutically acceptable salt thereof.

2. The formulation of claim 1, comprising Compound No. 1A:or a pharmaceutically acceptable salt thereof.

3. The formulation of claim 1, comprising Compound No. IB:or a pharmaceutically acceptable salt thereof.

4. The formulation of any one of the preceding claims, wherein the formulation is a capsule.

5. The formulation of any one of the preceding claims, further comprising a filler, a disintegrant, a glidant, and a lubricant.

6. The formulation of any one of the preceding claims, comprising: about 5.6±2.0% w / w, about 5.6±1.5% w / w, about 5.6±1.0% w / w, about 5.6±0.9% w / w, about 5.6±0.8% w / w, about 5.6±0.7% w / w, about 5.6±0.6% w / w, about 5.6±0.5% w / w, about 5.6±0.4% w / w, about 5.6±0.3% w / w, about 5.6±0.2% w / w, or about 5.6±0. 1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 5.0±2.0 mg, about 5.0±1.5 mg, about 5.0±1.0 mg, about 5.0±0.9 mg, about 5.0±0.8 mg, about 5.0±0.7 mg, about 5.0±0.6 mg, about 5.0±0.5 mg, about 5.0±0.4 mg, about 5.0±0.3 mg. about 5.0±0.2 mg, or about 5.0±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 27.8±5.0% w / w, about 27.8±4.0% w / w, about 27.8±3.0% w / w, about 27.8±2.0% w / w, about 27.8±1.5% w / w, about 27.8±1.0% w / w, about 27.8±0.9% w / w, about 27.8±0.8% w / w, about 27.8±0.7% w / w, about 27.8±0.6% w / w, about 27.8±0.5% w / w, about 27.8±0.4% w / w, about 27.8±0.3% w / w, about 27.8±0.2% w / w, or about 27.8±0.1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 25±5.0 mg, about 25±4.0 mg, about 25±3.0 mg, about 25±2.0 mg, about 25±1.5 mg, about 25±1.0 mg, about 25±0.9 mg, about 25±0.8 mg, about 25±0.7 mg, about 25±0.6 mg, about 25±0.5 mg, about 25±0.4 mg. about 25±0.3 mg, about 25±0.2 mg. or about 25±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 40±15% w / w, about 40±10% w / w, about 40±5.0% w / w, about 40±4.0% w / w, about 40±3.0% w / w, about 40±2.0% w / w, about 40±1.5% w / w, about 40±1.0% w / w, about 40±0.9% w / w, about 40±0.8% w / w, about 40±0.7% w / w, about 40±0.6% w / w, about 40±0.5% w / w, about 40±0.4% w / w. about 40±0.3% w / w, about 40±0.2% w / w, or about 40±0.1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; or about 100±15 mg, about 100±10 mg, about 100±5.0 mg, about 100±4.0 mg, about 100±3.0 mg, about 100±2.0 mg, about 100±1.5 mg, about 100±1.0 mg, about 100±0.9 mg, about 100±0.8 mg. about 100±0.7 mg, about 100±0.6 mg, about 100±0.5 mg. about 100±0.4mg, about 100+0.3 mg, about 100+0.2 mg, or about 100+0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof .

7. The formulation of any one of the preceding claims, wherein the filler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or cellulose.

8. The formulation of any one of the preceding claims, comprising: about 90.4±15% w / w, about 90.4±10% w / w, about 90.4±5.0% w / w, about 90.4±4.0% w / w, about 90.4±3.0% w / w. about 90.4±2.0% w / w, about 90.4±1.5% w / w, about 90.4±1.0% w / w, about 90.4±0.9% w / w, about 90.4±0.8% w / w, about 90.4±0.7% w / w, about 90.4±0.6% w / w, about 90.4±0.5% w / w, about 90.4±0.4% w / w, about 90.4±0.3% w / w, about 90.4±0.2% w / w, or about 90.4±0.1% w / w of microcrystalline cellulose; about 81.4±15 mg. about 81.4±10 mg, about 81.4±5.0 mg, about 81.4±4.0 mg, about 81.4±3.0 mg. about 81.4±2.0 mg, about 81.4±1.5 mg. about 81.4±1.0 mg, about 81.4±0.9 mg. about 81.4±0.8 mg, about 81.4±0.7 mg, about 81.4±0.6 mg, about 81.4±0.5 mg, about 81.4±0.4 mg, about 81.4±0.3 mg, about 81.4±0.2 mg, or about 81.4±0.1 mg of microcrystalline cellulose; about 68.2±15% w / w, about 68.2±10% w / w, about 68.2±5.0% w / w, about 68.2±4.0% w / w, about 68.2±3.0% w / w. about 68.2±2.0% w / w, about 68.2±1.5% w / w, about 68.2±1.0% w / w, about 68.2±0.9% w / w, about 68.2±0.8% w / w, about 68.2±0.7% w / w, about 68.2±0.6% w / w, about 68.2±0.5% w / w, about 68.2±0.4% w / w, about 68.2±0.3% w / w, about 68.2±0.2% w / w, or about 68.2±0.1% w / w of microcrystalline cellulose; about 61.4±15 mg. about 61.4±10 mg, about 61.4±5.0 mg, about 61.4±4.0 mg, about 61.4±3.0 mg, about 61.4±2.0 mg, about 61.4±1.5 mg, about 61.4±1.0 mg, about 61.4±0.9 mg, about 61.4±0.8 mg, about 61.4±0.7 mg, about 61.4±0.6 mg, about 61.4+0.5 mg, about 61.4+0.4 mg, about 61.4+0.3 mg, about 61.4+0.2 mg, or about 61.4+0.1 mg of microcrystalline cellulose; about 50±15% w / w, about 50+10% w / w, about 50+5.0% w / w, about 50±4.0% w / w, about 50+3.0% w / w, about 50+2.0% w / w, about 50+1.5% w / w. about 50+1.0% w / w, about 50+0.9% w / w, about 50+0.8% w / w, about 50+0.7% w / w, about 50+0.6% w / w, about 50+0.5% w / w, about 50+0.4% w / w, about 50+0.3% w / w, about 50±0.2% w / w, or about 50+0.1% w / w of microcrystalline cellulose; or about 125+15 mg. about 125±10 mg, about 125±5.0 mg, about 125±4.0 mg, about 125±3.0 mg, about 125+2.0 mg, about 125±1.5 mg, about 125+1.0 mg, about 125±0.9 mg,about 125±0.8 mg, about 125±0.7 mg, about 125±0.6 mg, about 125±0.5 mg, about 125±0.4 mg, about 125±0.3 mg, about 125±0.2 mg, or about 125±0.1 mg of microcrystalline cellulose.

9. The formulation of any one of the preceding claims, wherein the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate, chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

10. The formulation of any one of the preceding claims, comprising: about 3.0±2.0% w / w. about 3.0±1.5% w / w, about 3.0±1.0% w / w, about 3.0±0.9% w / w, about 3.0±0.8% w / w, about 3.0±0.7% w / w, about 3.0±0.6% w / w, about 3.0±0.5% w / w, about 3.0±0.4% w / w, about 3.0±0.3% w / w, about 3.0±0.2% w / w, or about 3.0±0.1% w / w of croscarmellose sodium; about 2.7±2.0 mg, about 2.7±1.5 mg, about 2.7±1.0 mg, about 2.7±0.9 mg, about 2.7±0.8 mg, about 2.7±0.7 mg, about 2.7±0.6 mg. about 2.7±0.5 mg, about 2.7±0.4 mg, about 2.7±0.3 mg, about 2.7±0.2 mg, or about 2.7±0.1 mg of croscarmellose sodium; about 8.0±5.0% w / w, about 8.0±4.0% w / w, about 8.0±3.0% w / w, about 8.0±2.0% w / w, about 8.0±1.5% w / w, about 8.0±1.0% w / w, about 8.0±0.9% w / w, about 8.0±0.8% w / w, about 8.0±0.7% w / w, about 8.0±0.6% w / w, about 8.0±0.5% w / w, about 8.0±0.4% w / w, about 8.0±0.3% w / w. about 8.0±0.2% w / w, or about 8.0±0.1% w / w of croscarmellose sodium; or about 20±5.0 mg, about 20±4.0 mg, about 20±3.0 mg, about 20±2.0 mg, about 20±l .5 mg, about 20±1.0 mg, about 20±0.9 mg, about 20±0.8 mg, about 20±0.7 mg, about 20±0.6 mg, about 20±0.5 mg, about 20±0.4 mg, about 20±0.3 mg, about 20±0.2 mg. or about 20±0.1 mg of croscarmellose sodium.

11. The formulation of any one of the preceding claims, wherein the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

12. The formulation of any one of the preceding claims, comprising: about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w of colloidal silicon dioxide; about 0.5±0.3 mg, about 0.5±0.2 mg, or about 0.5±0. 1 mg of colloidal silicon dioxide;about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w of colloidal silicon dioxide; or about 2.5±1.0 mg, about 2.5±0.9 mg, about 2.5±0.8 mg, about 2.5±0.7 mg, about 2.5+0.6 mg, about 2.5+0.5 mg, about 2.5±0.4 mg, about 2.5±0.3 mg, about 2.5±0.2 mg, or about 2.5±0.1 mg of colloidal silicon dioxide.

13. The formulation of any one of the preceding claims, wherein the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

14. The formulation of any one of the preceding claims, comprising: about 0.5±0.3% w / w, about 0.5±0.2% w / w, or about 0.5±0.1% w / w of magnesium stearate; about 0.5±0.3 mg, about 0.5±0.2 mg, or about 0.5±0.1 mg of magnesium stearate; about 1.0±0.5% w / w. about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0. 1% w / w of magnesium stearate; or about 2.5±1.0 mg, about 2.5±0.9 mg, about 2.5±0.8 mg, about 2.5±0.7 mg, about 2.5±0.6 mg, about 2.5±0.5 mg, about 2.5±0.4 mg, about 2.5±0.3 mg, about 2.5±0.2 mg, or about 2.5±0. 1 mg of the lubricant (e g., magnesium stearate.

15. The formulation of any one of the preceding claims, wherein the formulation is a tablet.

16. The formulation of any one of the preceding claims, comprising an intragranular mixture and an extragranular mixture.

17. The formulation of any one of the preceding claims, further comprising a fdler, a disintegrant, a glidant, a lubricant, and a binder.

18. The formulation of any one of the preceding claims, comprising: about 30.8±10% w / w, about 30.8±5.0% w / w, about 30.8±4.0% w / w, about 30.8±3.0% w / w, about 30.8±2.0% w / w, about 30.8±1.5% w / w, about 30.8±1.0% w / w, about 30.8±0.9% w / w, about 30.8±0.8% w / w, about 30.8±0.7% w / w, about 30.8±0.6% w / w, about 30.8±0.5% w / w, about 30.8±0.4% w / w, about 30.8±0.3% w / w, about 30.8±0.2% w / w, or about 30.8±0. 1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof;about 75±15 mg, about 75±10 mg, about 75±5.0 mg, about 75±4.0 mg, about 75±3.0 mg, about 75±2.0 mg, about 75±1.5 mg, about 75±1.0 mg, about 75±0.9 mg, about 75±0.8 mg, about 75±0.7 mg, about 75±0.6 mg, about 75±0.5 mg, about 75±0.4 mg, about 75±0.3 mg, about 75±0.2 mg, or about 75±0. 1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 100±15 mg, about 100±10 mg, about 100±5.0 mg, about 100±4.0 mg, about 100±3.0 mg. about 100±2.0 mg, about 100±1.5 mg. about 100±1.0 mg, about 100±0.9 mg. about 100±0.8 mg, about 100±0.7 mg, about 100±0.6 mg, about 100±0.5 mg, about 100±0.4 mg, about 100±0.3 mg, about 100±0.2 mg, or about 100±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 200±40 mg. about 200±30 mg, about 200±20 mg. about 200±15 mg, about 200±10 mg, about 200±5.0 mg, about 200±4.0 mg, about 200±3.0 mg, about 200±2.0 mg, about 200±1.5 mg, about 200±1.0 mg, about 200±0.9 mg, about 200±0.8 mg, about 200±0.7 mg, about 200±0.6 mg, about 200±0.5 mg, about 200±0.4 mg, about 200±0.3 mg, about 200±0.2 mg, or about 200±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 30.8±10% w / w, about 30.8±5.0% w / w, about 30.8±4.0% w / w, about 30.8±3.0% w / w, about 30.8±2.0% w / w, about 30.8±1.5% w / w, about 30.8±1.0% w / w, about 30.8±0.9% w / w, about 30.8±0.8% w / w, about 30.8±0.7% w / w, about 30.8±0.6% w / w, about 30.8±0.5% w / w, about 30.8±0.4% w / w, about 30.8±0.3% w / w, about 30.8±0.2% w / w, or about 30.8±0. 1% w / w of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 75±15 mg, about 75±10 mg, about 75±5.0 mg, about 75±4.0 mg, about 75±3.0 mg, about 75±2.0 mg, about 75±1.5 mg, about 75±1.0 mg, about 75±0.9 mg, about 75±0.8 mg, about 75±0.7 mg, about 75±0.6 mg, about 75±0.5 mg, about 75±0.4 mg. about 75±0.3 mg, about 75±0.2 mg, or about 75±0. 1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 100±15 mg, about 100±10 mg, about 100±5.0 mg, about 100±4.0 mg, about 100±3.0 mg, about 100±2.0 mg, about 100±1.5 mg, about 100±1.0 mg, about 100±0.9 mg, about 100±0.8 mg. about 100±0.7 mg, about 100±0.6 mg, about 100±0.5 mg. about 100±0.4 mg, about 100±0.3 mg, about 100±0.2 mg, or about 100±0.1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; or about 200±40 mg, about 200±30 mg, about 200±20 mg, about 200±15 mg, about 200±10 mg, about 200±5.0 mg, about 200±4.0 mg, about 200±3.0 mg, about 200±2.0 mg, about 200±1.5 mg, about 200±1.0 mg, about 200±0.9 mg, about 200±0.8 mg, about 200±0.7mg, about 200±0.6 mg, about 200±0.5 mg, about 200±0.4 mg, about 200±0.3 mg, about 200±0.2 mg, or about 200±0. 1 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof.

19. The formulation of any one of the preceding claims, wherein the filler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or cellulose.

20. The formulation of any one of the preceding claims, comprising: about 31.6±10% w / w, about 31.6±5.0% w / w, about 31.6±4.0% w / w, about 31.6±3.0% w / w, about 31.6±2.0% w / w, about 31.6±1.5% w / w, about 31.6±1.0% w / w, about 31.6±0.9% w / w, about 31.6±0.8% w / w, about 31.6±0.7% w / w, about 31.6±0.6% w / w, about 31.6±0.5% w / w, about 31.6±0.4% w / w, about 31.6±0.3% w / w, about 31.6±0.2% w / w, or about 31.6±0.1% w / w of microcrystalline cellulose; about 77±15 mg. about 77±10 mg, about 77±5.0 mg. about 77±4.0 mg, about 77±3.0 mg, about 77±2.0 mg, about 77±1.5 mg, about 77±1.0 mg, about 77±0.9 mg, about 77±0.8 mg, about 77±0.7 mg, about 77±0.6 mg, about 77±0.5 mg, about 77±0.4 mg, about 77±0.3 mg, about 77±0.2 mg, or about 77±0.1 mg of microcry stalline cellulose; about 103±20 mg. about 103±15 mg, about 103±10 mg, about 103±5.0 mg, about 103±4.0 mg, about 103±3.0 mg, about 103±2.0 mg, about 103±1.5 mg, about 103±1.0 mg, about 103±0.9 mg, about 103±0.8 mg, about 103±0.7 mg, about 103±0.6 mg, about 103±0.5 mg, about 103±0.4 mg, about 103±0.3 mg, about 103±0.2 mg, or about 103±0.1 mg of microcrystalline cellulose; or about 206±40 mg, about 206±30 mg, about 206±20 mg, about 206±15 mg, about 206±10 mg, about 206±5.0 mg, about 206+4.0 mg, about 206+3.0 mg, about 206+2.0 mg, about 206+1.5 mg, about 206+1.0 mg, about 206+0.9 mg, about 206±0.8 mg, about 206+0.7 mg, about 206±0.6 mg, about 206+0.5 mg, about 206+0.4 mg, about 206+0.3 mg, about 206±0.2 mg, or about 206+0. 1 mg of microcrystalline cellulose.

21. The formulation of any one of the preceding claims, wherein the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate, chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

22. The formulation of any one of the preceding claims, comprising: about 4.0±2.0% w / w, about 4.0±1.5% w / w, about 4.0±1.0% w / w, about 4.0±0.9% w / w, about 4.0±0.8% w / w, about 4.0±0.7% w / w, about 4.0±0.6% w / w, about 4.0±0.5% w / w, about 4.0±0.4% w / w, about 4.0±0.3% w / w, about 4.0±0.2% w / w, or about 4.0±0.1% w / w of croscarmellose sodium; about 9.6±4.0 mg. about 9.6±3.0 mg, about 9.6±2.0 mg. about 9.6±1.5 mg, about 9.6±1.0 mg, about 9.6±0.9 mg, about 9.6±0.8 mg, about 9.6±0.7 mg, about 9.6±0.6 mg, about 9.6±0.5 mg, about 9.6±0.4 mg, about 9.6±0.3 mg, about 9.6±0.2 mg, or about 9.6±0.1 mg of croscarmellose sodium; about 13±5.0 mg, about 13±4.0 mg, about 13±3.0 mg, about 13±2.0 mg, about 13±1.5 mg, about 13±1.0 mg, about 13±0.9 mg, about 13±0.8 mg, about 13±0.7 mg, about 13±0.6 mg, about 13±0.5 mg, about 13±0.4 mg, about 13±0.3 mg, about 13±0.2 mg, or about 13±0.1 mg of croscarmellose sodium; or about 26±10 mg, about 26±5.0 mg, about 26±4.0 mg. about 26±3.0 mg, about 26±2.0 mg, about 26±1.5 mg, about 26±1.0 mg. about 26±0.9 mg, about 26±0.8 mg, about 26±0.7 mg. about 26±0.6 mg, about 26±0.5 mg, about 26±0.4 mg, about 26±0.3 mg, about 26±0.2 mg, or about 26±0. 1 mg of croscarmellose sodium.

23. The formulation of any one of the preceding claims, wherein the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

24. The formulation of any one of the preceding claims, comprising: about 1.0±0.5% w / w, about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w of colloidal silicon dioxide; about 2.4±1.0 mg, about 2.4±0.9 mg, about 2.4±0.8 mg, about 2.4±0.7 mg, about 2.4±0.6 mg, about 2.4±0.5 mg, about 2.4±0.4 mg, about 2.4±0.3 mg. about 2.4±0.2 mg, or about 2.4±0.1 mg of colloidal silicon dioxide; about 3.2±1.0 mg, about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg, about 3.2±0.4 mg, about 3.2±0.3 mg, about 3.2±0.2 mg, or about 3.2±0.1 mg of colloidal silicon dioxide; orabout 6.4±3.0 mg, about 6.4±2.0 mg, about 6.4±1.0 mg, about 6.4±0.9 mg, about 6.4±0.8 mg, about 6.4±0.7 mg, about 6.4±0.6 mg. about 6.4±0.5 mg, about 6.4±0.4 mg, about 6.4±0.3 mg, about 6.4±0.2 mg, or about 6.4±0.1 mg of colloidal silicon dioxide.

25. The formulation of any one of the preceding claims, wherein the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer. magnesium stearate, or any combination thereof.

26. The formulation of any one of the preceding claims, comprising: about 1.0±0.5% w / w. about 1.0±0.4% w / w, about 1.0±0.3% w / w, about 1.0±0.2% w / w, or about 1.0±0.1% w / w of magnesium stearate; about 2.4±1.0 mg, about 2.4±0.9 mg, about 2.4±0.8 mg, about 2.4±0.7 mg, about 2.4±0.6 mg, about 2.4±0.5 mg, about 2.4±0.4 mg, about 2.4±0.3 mg, about 2.4±0.2 mg, or about 2.4±0.1 mg of magnesium stearate; about 3.2±1.0 mg. about 3.2±0.9 mg, about 3.2±0.8 mg, about 3.2±0.7 mg, about 3.2±0.6 mg, about 3.2±0.5 mg. about 3.2±0.4 mg. about 3.2±0.3 mg. about 3.2±0.2 mg, or about 3.2±0.1 mg of magnesium stearate; or about 6.4±3.0 mg, about 6.4±2.0 mg, about 6.4±1.0 mg, about 6.4±0.9 mg, about 6.4±0.8 mg, about 6.4±0.7 mg, about 6.4±0.6 mg, about 6.4±0.5 mg, about 6.4±0.4 mg, about 6.4±0.3 mg, about 6.4±0.2 mg, or about 6.4±0. 1 mg of magnesium stearate.

27. The formulation of any one of the preceding claims, wherein the binder comprises polyvinylpyrrolidone, copovidone, maize starch, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, dextrin, magnesium aluminum silicate, or sodium alginate.

28. The formulation of any one of the preceding claims, comprising: about 31.6±10% w / w, about 31.6±5.0% w / w, about 31.6±4.0% w / w, about 31.6±3.0% w / w, about 31.6±2.0% w / w. about 31.6±1.5% w / w, about 31.6±1.0% w / w, about 31.6±0.9% w / w, about 31.6±0.8% w / w, about 31.6±0.7% w / w, about 31.6±0.6% w / w, about 31.6±0.5% w / w, about 31.6±0.4% w / w, about 31.6±0.3% w / w, about 31.6±0.2% w / w, or about 31.6±0.1% w / w of partially pregelatinized maize starch; about 77±15 mg. about 77±10 mg, about 77±5.0 mg. about 77±4.0 mg, about 77±3.0 mg, about 77±2.0 mg, about 77±1.5 mg, about 77±1.0 mg, about 77±0.9 mg, about 77±0.8 mg,about 77+0.7 mg, about 77+0.6 mg, about 77+0.5 mg, about 77+0.4 mg, about 77+0.3 mg, about 77+0.2 mg, or about 77+0. 1 mg of partially pregelatinized maize starch; about 103+20 mg, about 103+15 mg, about 103±10 mg, about 103+5.0 mg, about 103+4.0 mg, about 103+3.0 mg, about 103+2.0 mg, about 103+1.5 mg, about 103+1.0 mg, about 103+0.9 mg, about 103+0.8 mg, about 103+0.7 mg, about 103+0.6 mg, about 103+0.5 mg, about 103+0.4 mg. about 103+0.3 mg. about 103+0.2 mg, or about 103+0. 1 mg of partially pregelatinized maize starch; or about 206+40 mg, about 206+30 mg, about 206+20 mg, about 206+15 mg, about 206+10 mg, about 206+5.0 mg, about 206+4.0 mg, about 206+3.0 mg, about 206+2.0 mg, about 206+1.5 mg. about 206+1.0 mg, about 206+0.9 mg, about 206+0.8 mg, about 206+0.7 mg, about 206+0.6 mg. about 206+0.5 mg, about 206+0.4 mg, about 206+0.3 mg, about 206+0.2 mg, or about 206+0.1 mg of partially pregelatinized maize starch.

29. A method for preparing the formulation of any one of the preceding claims.

30. A method of treating or preventing cancer in a subject, comprising administering to the subject the formulation of any one of the preceding claims.

31. The method or formulation of any one of the preceding claims, wherein the cancer is glioblastoma (GBM).

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