Inhalable hormone receptor agonist formulations

Abstract

When a pharmaceutical composition is delivered by oral ingestion of a capsule or tablet, it may take a long time to dissolve and reach the bloodstream. If a fatty food is consumed before ingestion of the capsule or tablet, absorption from the stomach may take longer, further slowing down the process. Provided herein are pharmaceutical compositions, kits containing pharmaceutical compositions, methods for treating diseases, and methods for making the compositions and kits described herein. The pharmaceutical compositions described herein are powdered pharmaceutical compositions. The powdered pharmaceutical compositions can be administered by the inhaler device described herein. The powdered pharmaceutical compositions can be administered by the gummies described herein.

Description

[Technical Field]

[0001] cross reference This application claims the benefit of U.S. Provisional Application No. 63 / 429,305, filed December 1, 2022, the entire disclosure of which is incorporated herein by reference. Incorporation by Reference

[0002] All publications, patents, and patent applications herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. In the event of a conflict between a term in this specification and a term in an incorporated reference, the term in this specification shall control. Sequence Listing

[0003] This application contains a Sequence Listing, which has been submitted electronically in ST.26 xml format and is hereby incorporated by reference in its entirety. The xml copy has a creation date of October 3, 2023, is named 199238-711601_SL.xml, and is 16,519 bytes in size. Summary of the Invention [Means for solving the problem]

[0004] Abstract Disclosed herein is a powdered pharmaceutical composition comprising a) particles of a pharmaceutically acceptable excipient and b) a plurality of spray-dried particles. In some embodiments, each particle of the plurality of spray-dried particles may be substantially encapsulated with a coating material. In some embodiments, the plurality of spray-dried particles substantially encapsulated with a coating material may comprise an agonist selected from the group consisting of a steroid or a pharmaceutically acceptable salt thereof, a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof. In some embodiments, among the plurality of spray-dried particles substantially encapsulated with a coating material, at least some of the spray-dried particles substantially encapsulated with a coating material may individually have a particle size ranging from about 1 micrometer to about 10 micrometers as measured by a particle analyzer using laser diffraction. In some embodiments, the coating material may include trehalose, hydroxypropyl methylcellulose (HPMC), fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropyl methylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, phospholipids, or any combination thereof. In some embodiments, the powdered pharmaceutical composition may further include a cannabinoid or a pharmaceutically acceptable salt thereof, including tetrahydrocannabinol delta-8, tetrahydrocannabinol delta-9, tetrahydrocannabinol delta-10, tetrahydrocannabinol delta-11, tetrahydrocannabinol delta-13, tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), full-spectrum THC, broad-spectrum THC, or a pharmaceutically acceptable salt thereof. In some embodiments, the spray-dried particles may include a steroid or a pharmaceutically acceptable salt thereof. In some embodiments, the steroid may be testosterone or a pharmaceutically acceptable salt thereof. In some embodiments, the steroid may be estrogen or a pharmaceutically acceptable salt thereof. In some embodiments, the steroid may be progesterone or a pharmaceutically acceptable salt thereof.In some embodiments, the spray-dried particles may comprise a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof. In some embodiments, the spray-dried particles may comprise a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof, and the glucagon-like peptide 1 receptor agonist may comprise semaglutide, liraglutide, or a pharmaceutically acceptable salt thereof. In some embodiments, the powdered pharmaceutical composition may be for inhalation or nasal administration. In some embodiments, the pharmaceutical composition may be in the form of a unit dose. In some embodiments, at least some of the particles of the pharmaceutically acceptable excipient may have an individual particle size ranging from about 1 micrometer to about 200 micrometers, from about 1 micrometer to about 10 micrometers, or from about 50 micrometers to about 200 micrometers, as measured by a particle analyzer using laser diffraction. In some embodiments, the particles may be blended to form a substantially homogeneous mixture. In some embodiments, the powdered pharmaceutical composition is contained in a capsule. In some embodiments, the capsule may be filled with about one-quarter to one-half of its volume with the powdered pharmaceutical composition. In some embodiments, the weight ratio of a) particles of a pharmaceutically acceptable excipient substantially encapsulated in a coating material to b) particles comprising an agonist or a pharmaceutically acceptable salt thereof may range from about 1:1 (w / w) to about 10,000:1 (w / w). In some embodiments, the weight ratio of a) particles of a pharmaceutically acceptable excipient to b) particles of an agonist or a pharmaceutically acceptable salt thereof may range from about 1:1 (w / w) to about 10:1 (w / w). In some embodiments, the portion of the capsule not containing the powdered pharmaceutical composition may contain a gas comprising at least partially an inert gas. In some embodiments, the capsule may comprise a hydroxypropyl methylcellulose (HPMC) capsule. In some embodiments, the capsule may be size 000, 00, 0, 1, 2, 3, or 4. In some embodiments, the capsule is size 3. In some embodiments, the powdered pharmaceutical composition may be contained in an inhaler unit. In some embodiments, a capsule may be contained in an inhaler unit.In some embodiments, the pharmaceutically acceptable excipient may include a carbohydrate, alginate, povidone, carbomer, flavoring, natural gum, silicone, alcohol, butter, wax, fatty acid, preservative, fumaryl diketopiperazine (FDKP), a pharmaceutically acceptable salt of any of these, or any combination thereof. In some embodiments, the pharmaceutically acceptable excipient may include a carbohydrate or a pharmaceutically acceptable salt thereof, and the carbohydrate or a pharmaceutically acceptable salt thereof may include lactose, microcrystalline cellulose, cellulose, mannitol, sorbitol, starch, starch glycolate, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, cyclodextrin, maltodextrin, croscarmellose sodium, corn starch, carrageenan, sorbitol, maltitol, glucose, a pharmaceutically acceptable salt of any of these, or any combination thereof. In some embodiments, the pharmaceutically acceptable excipient may include lactose or a pharmaceutically acceptable salt thereof. In some embodiments, the lactose may comprise milled lactose, sieved lactose, micronized lactose, spray-dried lactose, at least substantially anhydrous lactose, monohydrate lactose, a pharmaceutically acceptable salt thereof, or any combination thereof. In some embodiments, the powdered pharmaceutical compositions described herein retain at least about 90% of the agonist after 6 months when stored in a sealed container at 25°C and room air at a relative humidity of about 50 percent, as measured by HPLC. In some embodiments, the agonist may be present in an amount ranging from about 0.001 mg to about 20 mg. In some embodiments, the agonist may be in the form of a pharmaceutically acceptable salt thereof, which may be a hydrochloride, bitartrate, or borate salt. In some embodiments, the particles comprising the agonist may have a median diameter of less than about 5 μm, less than 6 μm, less than 7 μm, less than 8 μm, less than 9 μm, or less than 10 μm.

[0005] Also disclosed herein are kits that include the powdered pharmaceutical compositions disclosed herein, at least partially contained in a container.

[0006] Also disclosed herein are methods for treating a disease or condition in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of a first therapeutic agent comprising a powdered pharmaceutical composition disclosed herein by inhalation, thereby treating the disease or condition. In some embodiments, administration can be once daily, twice daily, three times daily, or four times daily. In some embodiments, the agonist can be a steroid or a pharmaceutically acceptable salt thereof. In some embodiments, the steroid or a pharmaceutically acceptable salt thereof can be testosterone or a salt thereof. In some embodiments, the disease or condition can be selected from the group consisting of obesity, low libido, underdevelopment of muscle mass, underdevelopment of secondary sexual characteristics, depression, underdevelopment of body hair, underdevelopment of voice change, underdevelopment of tendons, underdevelopment of ligaments, and underdevelopment of spermatogenesis. In some embodiments, the steroid or a pharmaceutically acceptable salt thereof can be estrogen or a salt thereof. In some embodiments, the powdered pharmaceutical composition may further comprise a cannabinoid or a pharmaceutically acceptable salt thereof, including tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and cannabidiolic acid (CBDA), cannabielsoin (CBE), cannabiditran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone, cannabifuran, cannabiglendol, cannabilipsol, cannabiditran, or any combination thereof. In some embodiments, the disease or condition can be selected from the group consisting of absence of female secondary sexual characteristics, decreased vaginal fluid, uterine hypoplasia, unwanted bone resorption, insufficient bone formation, undesirably low levels of body fat, thinning of the vaginal wall, infertility, ovulation regulation, menstrual regulation, endometriosis, depression, obsessive-compulsive disorder, and eating disorders. In some embodiments, the steroid or a pharmaceutically acceptable salt thereof can be progesterone or a salt thereof.In some embodiments, the disease or condition can be selected from the list consisting of uterine cancer, cervical cancer, failure to prevent pregnancy, failure to maintain pregnancy, unwanted premature birth, unwanted lactation during pregnancy, inadequate breast development for breastfeeding, skin aging, and libido regulation. In some embodiments, the agonist can be a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or condition can be selected from the group consisting of inadequate calcium retention, low muscle mass, obesity, inadequate visceral growth, high hepatic glucose uptake, inadequate hepatic gluconeogenesis, pancreatic islet dysfunction, inadequate immune system stimulation, poor cognitive function, Turner syndrome, chronic renal failure, Prader-Willi syndrome, intrauterine growth restriction, severe idiopathic short stature, AIDS-related muscle mass wasting, low body density, multiple sclerosis, obesity, fibromyalgia, heart failure, Crohn's disease, and ulcerative colitis. In some embodiments, the agonist may be a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or condition may be selected from the following: type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), obesity, overweight, coronary artery disease (CAD), dementia, coronary heart disease (CHD), ischemic heart disease (IHD), and myocardial ischemia. In some embodiments, the powdered pharmaceutical composition may be administered as needed or for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, or over a long period of time. In some embodiments, a second therapeutic agent or a pharmaceutically acceptable salt thereof may be administered. In some embodiments, the second therapeutic agent or a pharmaceutically acceptable salt thereof may be administered simultaneously or sequentially. In some embodiments, the second therapeutic agent or a pharmaceutically acceptable salt thereof may be included in the powdered pharmaceutical formulation. In some embodiments, the first therapeutic agent may include a steroid or a pharmaceutically acceptable salt thereof, and the second therapeutic agent may include a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof.In some embodiments, the subject may have been diagnosed with a disease or condition. In some embodiments, the diagnosis may involve the use of an in vitro diagnostic. In some embodiments, the in vitro diagnostic may be a companion diagnostic. In some embodiments, the inhalation may be oral inhalation, nasal administration, or any combination thereof.

[0007] Also disclosed herein is a powdered pharmaceutical composition comprising particles of a pharmaceutically acceptable carrier and a plurality of spray-dried particles. In some embodiments, each particle of the plurality of spray-dried particles can be substantially unencapsulated. In some embodiments, the plurality of substantially unencapsulated spray-dried particles can comprise an agonist selected from the group consisting of a steroid or a pharmaceutically acceptable salt thereof, a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof. In some embodiments, among the plurality of spray-dried particles, the plurality of spray-dried particles can have a mass median aerodynamic diameter of less than 5 μm when aerosolized and a fine particle fraction of at least about 40%. In some embodiments, the pharmaceutically acceptable carrier may include trehalose, hydroxypropyl methylcellulose (HPMC), fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropyl methylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, phospholipids, or any combination thereof. In some embodiments, the powdered pharmaceutical composition may contain at least about 2% to about 20% of an agonist. In some embodiments, the agonist may be a steroid or a pharmaceutically acceptable salt thereof. In some embodiments, the steroid or a pharmaceutically acceptable salt thereof may be testosterone or a pharmaceutically acceptable salt thereof. In some embodiments, the steroid or a pharmaceutically acceptable salt thereof may be estrogen or a pharmaceutically acceptable salt thereof. In some embodiments, the steroid or a pharmaceutically acceptable salt thereof may be progesterone or a pharmaceutically acceptable salt thereof. In some embodiments, the agonist may be a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof. In some embodiments, the agonist may be a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof. In some embodiments, the powdered pharmaceutical composition may contain the agonist in an amount of about 3 mg to about 30 mg. In some embodiments, the powdered pharmaceutical composition may contain the agonist in an amount of at least about 0.25 mg.In some embodiments, the powdered pharmaceutical composition may be encapsulated to provide a delivered dose of at least about 0.075 mg. [Brief explanation of the drawings]

[0008] [Figure 1A] FIG. 1A shows a dry powder inhaler device for delivering a powdered pharmaceutical composition to the alveoli, and FIG. 1B shows a nasal inhalation device for nasal delivery of a powdered pharmaceutical composition to the alveoli. [Figure 1B] Same as above.

[0009] [Figure 2] FIG. 2 illustrates the use of a dry powder inhaler device to deliver a powdered pharmaceutical composition.

[0010] [Figure 3] Figure 3 shows a spray drying manufacturing system that includes a closed spray drying vessel that receives a solution containing a drug dissolved or mixed in a suitable solvent, and produces solid particles from the drug-containing solution.

[0011] [Figure 4] FIG. 4 shows a protective cap for a dry powder inhaler device.

[0012] [Figure 5] FIG. 5 shows a rotatable mouthpiece of a dry powder inhaler device.

[0013] [Figure 6] FIG. 6 shows the lower base chamber housing of a dry powder inhaler device.

[0014] [Figure 7] FIG. 7 shows a side button operatively connected to a sharp surface for use in a dry powder inhaler device to puncture a capsule containing a dry powder pharmaceutical composition.

[0015] [Figure 8] FIG. 8 shows the base plate of a dry powder inhaler device.

[0016] [Figure 9] FIG. 9 shows a dry powder inhaler device for delivering a powdered pharmaceutical composition to the alveoli.

[0017] [Figure 10] FIG. 10 shows a spray drying manufacturing system that includes a closed spray drying chamber that receives a solution containing an active ingredient, an encapsulating polymer, and a suitable solvent. DETAILED DESCRIPTION OF THE INVENTION

[0018] Detailed Description overview When pharmaceutical compositions are delivered by oral ingestion of capsules or tablets, they may take a long time to dissolve and reach the bloodstream.If fatty foods are eaten before taking capsules or tablets, absorption from the stomach may take longer, further slowing down the process.By spray-drying pharmaceutical compositions and introducing the spray-dried pharmaceutical compositions into the lungs by inhalation, the time required for the medicine to reach the bloodstream can be significantly reduced.In addition, the dosage level can be reduced compared with oral tablet or capsule equivalents.

[0019] Provided herein are methods and pharmaceutical formulations for treating conditions characterized by low androgen levels, such as obesity, low libido, underdevelopment of muscle mass, failure to develop secondary sexual characteristics, depression, underdevelopment of body hair, failure to progress through voice change, underdevelopment of tendons, underdevelopment of ligaments, and spermatogenesis.

[0020] Also provided herein are methods and pharmaceutical formulations for treating conditions characterized by low estrogen levels, such as regulation of the female reproductive system, absence of female secondary sexual characteristics, decreased vaginal fluids, uterine hypoplasia, unwanted bone resorption, insufficient bone formation, undesirably low levels of body fat, thinning of the vaginal wall, infertility, ovulation regulation, menstrual regulation, endometriosis, depression, obsessive-compulsive disorder, eating disorders, and low libido, which can be seen in both men and women.

[0021] Also provided herein are methods and pharmaceutical formulations for treating conditions characterized by low progesterone levels, such as uterine cancer, cervical cancer, inability to prevent or maintain pregnancy, unwanted premature birth, unwanted lactation during pregnancy, inadequate breast development for breastfeeding, skin aging, libido regulation, and the like.

[0022] Also provided herein are agonists that bind to steroid hormone receptors, which can be androgen receptors, estrogen receptors, and progesterone receptors.

[0023] Also provided herein is the agonist that binds to estrogen steroid receptor.Estrogen receptor can include nuclear estrogen receptors such as Erα and Erβ and membrane-type estrogen receptors such as GPR30, ER-X, Gq-mER.Also provided herein is the agonist that binds to progesterone steroid receptors such as NR3C3 and the agonist that binds to androgen steroid receptors such as NR3C4.

[0024] In particular, the preparation of pharmaceutical compositions is also disclosed herein.In some cases, pharmaceutical compositions can be used to deliver steroid receptor agonists for the treatments listed above.In some cases, steroid receptor agonists are drugs that can bind to steroid receptors.Drugs can be delivered as dry powder drugs, and use inhalation or nasal administration as administration routes.In some cases, drugs can be microencapsulated.In some cases, drugs can be non-microencapsulated.

[0025] Also provided herein is a powder composition comprising at least partially encapsulated metformin particles.In some cases, the at least partially encapsulated metformin can be incorporated into a gummy candy and administered to a subject to treat diseases or conditions such as type 2 diabetes.In some cases, the gummy candy is at least partially encapsulated in an enteric coating such as methyl methacrylate.

[0026] Also provided herein are pharmaceutical compositions, kits containing pharmaceutical compositions, methods for treating and preventing diseases, and methods for making the compositions and kits described herein.The pharmaceutical compositions described herein can be made using various methods for synthesizing, manipulating, and administering particles.In some aspects, the pharmaceutical compositions described herein are powdered pharmaceutical compositions. definition

[0027] Unless otherwise defined, all terms of art, notations, and other scientific and technical terms or terminology used herein are intended to have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms having a commonly understood meaning are defined herein for clarity and / or ready reference, and the inclusion of such definitions herein should not necessarily be construed as representing a substantial departure from the definition commonly understood in the art.

[0028] Throughout this application, various aspects may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present disclosure. Thus, the description of a range should be considered to specifically disclose all possible subranges and individual values ​​within that range. For example, a description of a range of 1 to 6 should be considered to specifically disclose subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, and 3 to 6, as well as individual numbers within that range, such as 1, 2, 3, 4, 5, and 6. This is true regardless of the breadth of the range.

[0029] As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, the term "a sample" includes multiple samples, including mixtures thereof.

[0030] The terms "determining," "measuring," "evaluating," "assessing," "assaying," and "analyzing" are often used interchangeably herein to refer to forms of measurement and include determining whether an element is present or not (e.g., detecting). These terms can include quantitative determinations, qualitative determinations, or both quantitative and qualitative determinations. Assessments can be either relative or absolute assessments. "Detecting the presence of" includes determining the amount of something present, as well as determining whether it is present or absent.

[0031] The terms "subject," "individual," "host," or "patient" are often used interchangeably herein. A "subject" can be a biological entity containing the genetic material to be expressed. The biological entity can be a plant, an animal, or a microorganism, including, for example, bacteria, viruses, fungi, and protozoa. A subject can be tissues, cells, and their progeny of a biological entity obtained in vivo or cultured in vitro. A subject can be a mammal. A mammal can be a human. A subject can be a subject who has been diagnosed with a disease or who is suspected of being at high risk for a disease. In some cases, a subject need not necessarily be a subject who has been diagnosed with a disease or who is suspected of being at high risk for a disease.

[0032] "Homology" or "identity" or "similarity" can refer to the sequence similarity between two peptides or two nucleic acid molecules. Homology can be determined by comparing positions within each sequence, which can be aligned for comparison purposes. If a position in the compared sequences is likely to be occupied by the same base or amino acid, the molecules can be homologous at that position. The degree of homology between sequences can be a function of the number of matching or homologous positions shared by the sequences. An "unrelated" or "non-homologous" sequence shares less than 40% identity, or alternatively less than 25% identity, with one of the sequences of the present disclosure. Sequence homology can refer to the % identity of a sequence to a reference sequence. In practice, whether any particular sequence may be at least 50%, 60%, 70%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98% or 99% identical to any sequence described herein (which may correspond to a particular nucleic acid sequence described herein) can be routinely determined by using a known computer program, such as the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix®, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wis. 53711), to determine whether a particular sequence is, for example, 95% identical to a reference sequence. When using Bestfit or any other sequence alignment program to determine whether a particular sequence is, for example, 95% identical to a reference sequence, parameters can be set to calculate the percentage of identity over the entire length of the reference sequence and to allow gaps in sequence homology of up to 5% across the entire reference sequence.

[0033] In some cases, the identity between a reference sequence (query sequence) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. 6:237-245 (1990)). In some embodiments, the parameters of certain embodiments in which identity can be narrowly interpreted and used for FASTDB amino acid alignment can include: scoring scheme = PAM (Percent Accepted Mutations) 0, k-tuple = 2, mismatch penalty = 1, joining penalty = 20, randomization group length = 0, cutoff score = 1, window size = sequence length, gap penalty = 5, gap size penalty = 0.05, window size = 500 or the length of the subject sequence, whichever is shorter. According to this embodiment, if the subject sequence may be shorter than the query sequence due to N- or C-terminal deletions rather than internal deletions, manual corrections can be made to the results to take into account the fact that the FASTDB program does not consider the N- and C-terminal truncations of the subject sequence when calculating the global percent identity.For subject sequences that are N- and C-terminally truncated compared to the query sequence, the percent identity can be corrected by calculating the number of query sequence residues that may exist outside the N- and C-termini of the subject sequence and may not match / align with the corresponding subject residues as a percentage of the total bases of the query sequence.Whether a residue can match / align can be determined by the results of FASTDB sequence alignment.This percentage is then subtracted from the percent identity calculated by the FASTDB program using specified parameters to arrive at a final percent identity score.This final percent identity score can be used for the purposes of this embodiment. In some cases, only residues at the N- and C-termini of the subject sequence that may not match / align with the query sequence can be considered for manually adjusting the percent identity score. That is, only query residue positions outside the most N- and C-terminal residues of the subject sequence can be considered for this manual correction. For example, a 90-residue subject sequence can be aligned with a 100-residue query sequence to determine percent identity. There is a deletion at the N-terminus of the subject sequence, and therefore, the FASTDB alignment does not show a match / alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (the number of unmatched residues at the N- and C-termini / the total number of residues in the query sequence), and therefore, 10% can be subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 residues are perfectly matched, the final percent identity can be 90%. In another example, a 90-residue subject sequence can be compared with a 100-residue query sequence. This time, the deletion may be an internal deletion, and therefore there may be no residues at the N- or C-termini of the subject sequence that may not match / align with the query. In this case, the percent identity calculated by FASTDB cannot be manually corrected. Again, only residue positions outside the N- and C-termini of the subject sequence displayed in the FASTDB alignment that may not match / align with the query sequence can be manually corrected.

[0034] The terms "substantially" or "essentially" can refer to the qualitative condition of exhibiting the entire or nearly entire extent or degree of a desired feature or characteristic. In some cases, substantially encapsulated can refer to nearly complete encapsulation of a substance or compound. For example, substantially encapsulated can include particles that are at least about 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% encapsulated. In some cases, substantially can refer to at least about 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% of the entire extent or degree of a desired feature or characteristic.

[0035] The term "at least partially" can refer to a qualitative condition indicating a partial extent or degree of a desired feature or characteristic. In some cases, at least partially encapsulated can refer to partial encapsulation of a substance or compound. For example, at least partially encapsulated can include particles that are at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% encapsulated.

[0036] The term "in vivo" may be used to describe events that take place inside a subject's body.

[0037] The term "ex vivo" may be used to describe an event that occurs outside of a subject's body. An "ex vivo" assay cannot be performed on a subject. Instead, an "ex vivo" assay may be performed on a sample that has been separated from a subject. An example of an "ex vivo" assay performed on a sample would be an "in vitro" assay.

[0038] The term "in vitro" can be used to describe events that occur contained in a container for holding experimental reagents and thus may be separated from the living biological source organism from which the material is obtained. In vitro assays can include cell-based assays that use live or dead cells. In vitro assays can also include cell-free assays that do not use intact cells.

[0039] As used herein, the term "about" a number may refer to a number plus or minus 10% of that number. The term "about" a range may refer to the minimum value of the range minus 10% and the maximum value of the range plus 10%.

[0040] As used herein, the "derivative" of a compound disclosed herein may refer to a chemical substance that is structurally related to the compound disclosed herein. A derivative may be produced from a structurally related parent compound in one or more steps. The overall physical and chemical properties of a derivative may be similar to those of the parent compound. A derivative may be, for example, an analog or a homolog.

[0041] As used herein, the terms "treatment" or "treating" are used in reference to a pharmaceutical or other intervention regimen to obtain a beneficial or desired result in a recipient. Beneficial or desired results include, but are not limited to, therapeutic benefit and / or prophylactic benefit. Therapeutic benefit can refer to the eradication or amelioration of the symptoms or underlying disorder being treated. Therapeutic benefit can also be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such that an improvement is observed in the subject, even though the subject may still be suffering from the underlying disorder. Prophylactic effects include delaying, preventing, or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof. With regard to prophylactic benefit, subjects at risk of developing a particular disease or reporting one or more physiological symptoms of a disease may receive treatment even if the disease has not been diagnosed.

[0042] As used herein, the terms "administration" and "administering" can refer to the manner in which an active agent is brought to a subject. Administration can be accomplished by various routes, such as oral, parenteral, transdermal, inhalation, implantation, etc.

[0043] As used herein, the term "pulmonary administration" can refer to any method of administration (either nasally or orally) in which an active agent can be administered via the pulmonary route by inhalation of an aerosolized liquid or powder form. Such aerosolized liquid or powder forms are traditionally intended to substantially release and / or deliver the active agent to the mucosa and epithelium of the lungs. In the context of the present disclosure, the active agent is in powder form.

[0044] As used herein, the term "nominal load" or "total load" can refer to the total amount of a formulation enclosed or divided for administration to a subject. For example, a nominal load is the total amount of a powder formulation contained in a capsule for use in an inhaler.

[0045] As used herein, the term "nominal dose" or "total dose" can refer to the total amount or mass of an active agent enclosed or divided for administration to a subject. For example, a nominal dose is the total amount of active agent contained in a capsule for use in an inhaler.

[0046] As used herein, the term "emitted dose" (ED(%)) may refer to the percentage of the mass of active agent emitted from a dry powder inhaler aerosolization device relative to the mass of the nominal dose. Powders that exhibit high flow rates often result in a higher ED(%).

[0047] As used herein, the terms "fine particle fraction" or "fine particle fraction from emitted dose" (%FPF(ED)) can refer to the percentage of the mass of active agent having an aerodynamic diameter below about 10 μm or 5 μm relative to the mass of the emitted dose. FPF is often used to assess the efficiency of aerosol deagglomeration.

[0048] As used herein, the term "respirable fraction" (RF(%)) may refer to the percentage of the mass of an active agent below a certain aerodynamic cutoff size relative to the mass of the nominal dose. It is also known as the fine particle fraction from the total dose (FPF(TD)). The fine particle fraction can also be calculated as a percentage of the emitted dose (FPF(ED)). The respirable fraction represents the proportion of the powder aerosol that can penetrate the deep airways. In some cases, the RF cutoff size may be an aerodynamic diameter of less than about 10 μm, less than about 7 μm, or less than about 5 μm. The respirable fraction can be determined using an inertial sampling device.

[0049] As used herein, the term "mass median aerodynamic diameter" (MMAD) refers to the mass median aerodynamic diameter of a particle in the atmosphere, where 50% of the particles, by mass, are larger and 50% are smaller than that diameter. In other words, the mass median aerodynamic diameter is the median of the aerodynamic particle size distribution as a function of particle mass. The percentage of mass less than a specified aerodynamic diameter is plotted logarithmically against the aerodynamic diameter. The MMAD is taken as the intersection of the line with the 50% cumulative percent. Computer methods can also be applied.

[0050] As used herein, the terms "unit dose" and "dosage form" may be used interchangeably and may refer to a pharmaceutical product in a form sold for use, having a specific mixture of active and inactive ingredients or excipients, having a specific configuration, and dispensed into specific doses to be delivered. The term "unit dose" may sometimes encompass non-reusable packaging, although the FDA distinguishes between a unit dose "package" and a "preparation." More than one unit dose may refer to separate pharmaceutical products packaged together, or to a single pharmaceutical product containing multiple drugs and / or doses. The term "unit dose" may also sometimes refer to the particles that make up a pharmaceutical composition, and any related mixtures. The type of unit dose may vary depending on the route of administration for drug delivery and the substance(s) to be delivered. A solid unit dose may be a dose of a solid form of a chemical compound used as a pharmaceutically acceptable drug or agent intended for administration or consumption.

[0051] As used herein, the term "fine particle fraction" or "fine particle fraction from an emitted dose" can refer to the mass of active agent having an aerodynamic diameter of less than about 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, or 10 μm. In some cases, the cutoff size can be an aerodynamic diameter of less than or equal to about 5 μm. In some cases, the cutoff size can be an aerodynamic diameter of less than or equal to about 6.4 μm. In some cases, the cutoff size can be an aerodynamic diameter of less than or equal to about 7 μm, or less than or equal to about 8 μm. In some cases, the fine particle fraction can often be used to evaluate the efficiency of aerosol deagglomeration. In some cases, the fine particle fraction can be the percentage of the mass of active agent having an aerodynamic diameter of less than about 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, or 10 μm relative to the mass of the emitted dose. In some cases, the fine particle fraction can be the percentage of mass of active agent relative to mass of the emitted dose that has an aerodynamic diameter of greater than about 5 μm, greater than 6 μm, greater than 7 μm, greater than 8 μm, greater than 9 μm, or greater than 10 μm. In some cases, the fine particle fraction can be the percentage of mass of active agent relative to mass of the emitted dose that has an aerodynamic diameter of about 1 μm to about 10 μm, 1 μm to about 5 μm, 3 μm to about 6 μm, 4 μm to about 7 μm, 6 μm to about 12 μm, or about 7 μm to about 10 μm. For example, the compositions described herein, when aerosolized, may have a solubility of greater than, less than, or equal to about 20%, greater than, less than, or equal to 20%, greater than, less than, or equal to 25%, greater than, less than, or equal to 25%, greater than, less than, or equal to 30%, greater than, less than, or equal to 31%, greater than, less than, or equal to 32%, greater than, less than, or equal to 32%, greater than, less than, or equal to 33%, greater than, less than, or equal to 34%, greater than, less than, or equal to 35%, greater than, less than, or equal to 36%, greater than, less than, or equal to 37%, greater than, less than, or equal to 38%, greater than, less than, or equal to 38%, greater than, less than, or equal to 39%, greater than, less than, or equal to 40%,or equal to 40%, greater than 41%, less than 41%, or equal to 41%, greater than 42%, less than 42%, or equal to 42%, greater than 43%, less than 43%, or equal to 43%, greater than 44%, less than 44%, or equal to 44%, greater than 45%, less than 45%, or equal to 45%, greater than 46%, less than 46%, or equal to 46%, greater than 47%, less than 47%, or equal to 47%, greater than 48%, less than 48%, or equal to 48%, greater than 49% or less than 49% , or equal to 49%, greater than 50%, less than 50%, or equal to 50%, greater than 51%, less than 51%, or equal to 51%, greater than 52%, less than 52%, or equal to 52%, greater than 53%, less than 53%, or equal to 53%, greater than 54%, less than 54%, or equal to 54%, greater than 55%, less than 55%, or equal to 55%, greater than 56%, less than 56%, or equal to 56%, greater than 57%, less than 57%, or equal to 57%, greater than 58% or less than 58% , or equal to 58%, greater than 59%, less than 59%, or equal to 59%, greater than 60%, less than 60%, or equal to 60%, greater than 61%, less than 61%, or equal to 61%, greater than 62%, less than 62%, or equal to 62%, greater than 63%, less than 63%, or equal to 63%, greater than 64%, less than 64%, or equal to 64%, greater than 65%, less than 65%, or equal to 65%, greater than 66%, less than 66%, or equal to 66%, greater than 67%, or less than 67% The fine particle fraction may be less than or equal to 67%, greater than 68%, less than or equal to 68%, greater than 69%, less than or equal to 69%, greater than 70%, less than or equal to 70%, greater than 75%, less than or equal to 75%, greater than 80%, less than or equal to 80%, greater than 85%, less than or equal to 85%, greater than 90%, less than or equal to 90%, or greater than 95%, less than or equal to 95%.

[0052] The terms "therapeutic agent," "active agent," "drug substance," "API," "pharmaceutically active agent," and "pharmaceutical product," and "drug" may be used interchangeably herein to refer to a substance having a pharmaceutical, pharmacological, psychosomatic, or therapeutic effect. Furthermore, when these terms are used, or when a particular active agent is specifically identified by name or category, it is understood that such listing is intended to encompass the active agent itself, as well as pharmaceutically acceptable, pharmacologically active derivatives thereof or compounds closely related thereto, including, but not limited to, salts, pharmaceutically acceptable salts, N-oxides, prodrugs, active metabolites, isomers, fragments, solvates (e.g., hydrates), polymorphs, pseudopolymorphs, and esters.

[0053] As used herein, "pharmaceutically acceptable salts" may refer to drug molecules used as pharmaceuticals that can be formed into their salt form as weak acids or weak bases, most often chemically prepared as hydrochloride, sodium salt, or sulfate salts. By synthesizing drug products as salts, the solubility of the drug can be enhanced, its absorption into the bloodstream can be promoted, and its therapeutic effect can be enhanced. Pharmaceutically acceptable salts can also facilitate the development of controlled-release dosage forms, improve the stability of the drug, extend its shelf life, enhance targeted drug delivery, and improve drug efficacy.

[0054] As used herein, "laser diffraction" may refer to a method for particle size analysis that involves irradiating a collection of particles with laser light, causing it to scatter, and collecting the scattered light with a spatially arranged detector array. The signal from the detector may be a pattern of scattered / diffracted light versus angle. This pattern may be generated by illuminating a large number of particles simultaneously with a laser light source, with all of their individual scattered / diffracted light rays being mixed at each detector element.

[0055] As used herein, "particle size analyzer" may refer to an instrument for particle size analysis, particle size measurement, or simply particle size classification.

[0056] As used herein, "particle size analysis" may refer to a technical procedure or a collection of experimental techniques for determining the size range and / or average (mean), median, or mode of the size of particles or droplets in a powder or liquid sample.

[0057] As used herein, "time to peak plasma concentration" can refer to the time it takes for a drug to reach its peak plasma concentration. Peak plasma concentration can usually be defined as the plasma concentration achieved by a drug in a particular compartment or test area of ​​the body after administration of the drug and before a second dose is administered.

[0058] As used herein, "HPLC" may refer to high performance liquid chromatography (formerly known as high pressure liquid chromatography), which is a technique in analytical chemistry used to separate, identify, and quantify individual components in a mixture. HPLC may be a common technique used in pharmaceutical development, as it may be a way to ensure product purity.

[0059] As used herein, an "effective amount" or "therapeutically effective amount" of a drug refers to a non-toxic but sufficient amount of drug to achieve a therapeutic result in the treatment of a condition for which the drug is known to be effective. It is understood that various biological factors can affect the ability of a substance to perform its intended role. Thus, an "effective amount" or "therapeutically effective amount" may depend, in part, on such biological factors. Furthermore, while the achievement of a therapeutic effect can be measured by a physician or other qualified medical practitioner using assessments known in the art, it is understood that individual differences and response to treatment can make the achievement of a therapeutic effect a somewhat subjective determination. Determining an effective amount is well within the ordinary skill in the art of pharmacy and medicine.

[0060] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. Pharmaceutical preparations

[0061] Disclosed herein are devices, systems and methods for making, encapsulating and delivering stable powdered pharmaceutical compositions.The active ingredient of these stable powdered formulations can comprise steroid receptor agonists.The active ingredient can further comprise additional ingredients as disclosed below.In certain cases, dry powdered compositions can comprise inactive ingredients such as excipients, carriers and / or diluents.

[0062] In certain cases, the dry powder pharmaceutical composition may be inhalable. For example, the dry powder pharmaceutical composition may be administered by a dry powder inhaler. In other cases, the dry powder pharmaceutical composition may be for oral administration. For example, the dry powder pharmaceutical composition may be administered as a capsule-in-capsule formulation. In another example, the dry powder pharmaceutical composition may be administered as multilayered microencapsulated particles. Active ingredients and pharmaceutically acceptable salts

[0063] A drug substance is intended to be used in the manufacture of a drug product and can be any substance or mixture of substances that, when used to make a drug, becomes the active ingredient of the drug product. Such substances can be intended to provide pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body. In some embodiments, the drug substance or its salt can be formulated as a powder. For example, the inhalable hormone receptor agonist formulations disclosed herein can be formulated as a powder using the methods described herein. In some cases, the active ingredient comprises a pharmaceutical compound. In some cases, the pharmaceutical compound comprises an active ingredient.

[0064] In certain embodiments, the active ingredient(s) may exist in different crystalline forms. Different crystalline forms of the same compound may affect one or more physical properties, such as stability, solubility, melting point, bulk density, flow properties, bioavailability, etc. steroid receptor agonists

[0065] In some embodiments, the drug substance may comprise a steroid receptor agonist or its pharmaceutically acceptable salt.In some cases, the steroid receptor agonist is referred to herein as a steroid.In some embodiments, the steroid receptor agonist may be directed to an androgen receptor, such as NR3C4.In some embodiments, the steroid receptor agonist may be directed to an estrogen receptor, such as Erα, Erβ, GPR30, ER-X, Gq-mER, or a combination thereof.In some embodiments, the steroid receptor agonist may be directed to a progesterone receptor, such as NR3C3.

[0066] In certain cases, the steroid receptor agonist is steroid, for example, pregnenolone, progesterone, deoxycorticosterone, corticosterone, aldosterone, 17α-hydroxypregnenolone, 17α-progesterone, 11-deoxycortisol, cortisol, dehydroepiandrosterone, androstenedione (A4), androstenediol (A5), testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), estrone, estradiol, any salt thereof, and any derivative thereof.In some cases, the steroid receptor agonist is testosterone or its salt.In some cases, testosterone can include testosterone enanthate, testosterone cypionate, testosterone propionate, testosterone undecanoate, methyltestosterone, or any combination thereof.

[0067] In certain cases, the steroid is an androgen. Androgens can be considered any natural or synthetic steroid hormone that regulates the development and maintenance of male sexual characteristics in vertebrates by binding to the androgen receptor. This can include the embryological development of male genitalia and the onset of male secondary sexual characteristics at puberty. Androgens can be synthesized in the testes, ovaries, and adrenal glands. Adrenal androgens are composed of 19-carbon steroids synthesized in the zona reticularis, the innermost layer of the adrenal cortex. Adrenal androgens function as weak steroids (although some are precursors), and a subset includes dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A4), and androstenediol (A5), combinations thereof, or salts or derivatives thereof.

[0068] Androstenedione (A4) is an androgenic steroid produced in the testes, adrenal cortex, and ovaries. It is metabolically converted to testosterone and other androgens and is also the parent structure of estrone. Androstenediol (A5) is a steroid metabolite of DHEA and a precursor to the sex hormones testosterone and estradiol. Androsterone is a chemical by-product created during the breakdown of androgens or derived from progesterone. Androsterone also exerts a mild masculinizing effect, but its potency is sevenfold less than that of testosterone. Androsterone is found in approximately equal amounts in plasma and urine in both males and females. Dihydrotestosterone (DHT), a metabolite of testosterone, is a more potent androgen than testosterone due to its stronger binding to the androgen receptor. DHT is produced in the skin and reproductive tissues.

[0069] In certain cases, the steroid is an estrogen. Estrogens can be considered a category of sex hormones responsible for the development and regulation of the female reproductive system and secondary sexual characteristics. These include estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4), which may be known as estranes. Estrogens of the present disclosure may include combinations of estranes, their salts, and / or estran derivatives. The estrogenic steroid hormones estradiol, estrone, and estriol are estra-1,3,5(10)-trienes. All of the various forms of estrogen are synthesized from androgens, particularly testosterone and androstenedione, by the aromatase enzyme. Secondary endogenous estrogens that do not involve aromatase in their biosynthesis include 27-hydroxycholesterol, dehydroepiandrosterone (DHEA), 7-oxo-DHEA, 7α-hydroxy-DHEA, 16α-hydroxy-DHEA, 7β-hydroxyepiandrosterone, androstenedione (A4), androstenediol (A5), 3α-androstanediol, and 3β-androstanediol. These estrogens of the present disclosure may include combinations thereof, salts thereof, or derivatives thereof. The secondary endogenous estrogens that do not involve aromatase in biosynthesis include 27-hydroxycholesterol, dehydroepiandrosterone (DHEA), 7-oxo-DHEA, 7α-hydroxy-DHEA, 16α-hydroxy-DHEA, 7β-hydroxyepiandrosterone, androstenedione (A4), androstenediol (A5), 3α-androstanediol, and 3β-androstanediol.The present disclosure can also include combinations thereof, their salts, and / or derivatives of these secondary endogenous estrogens.In some cases, the compositions herein can include estrone, estradiol, estriol, estetrol, any salt thereof, any derivative thereof, or any combination thereof.

[0070] In some cases, the steroid is progestin.Progestin steroid hormone can include progesterone (P4), 16α-hydroxyprogesterone (16α-OHP), 17α-hydroxyprogesterone (17α-OHP), 20α-dihydroprogesterone (20α-DHP), 20β-dihydroprogesterone (20β-DHP), 5α-dihydroprogesterone (5α-DHP), 5β-dihydroprogesterone (5β-DHP), 3β-dihydroprogesterone (3β-DHP), 11-deoxycorticosterone (DOC), 5α-dihydrodeoxycorticosterone (5α-DHDOC), their combination, their salt or their derivative.In some cases, the composition herein can contain progestin. In some cases, the progestin may include pregnane, estrange, gonane, any salt thereof, or any combination thereof. In some cases, the progestin may include norethindrone, norethindrone acetate, ethynodiol, ethynodiol acetate, levonorgestrel, norgestrel, desogestrel, norgestimate, drospirenone, norethynodrel, or any combination thereof. In some cases, the progestin may include medroxyprogesterone acetate, nomegestrol acetate, gestodene, or any combination thereof. In some cases, the compositions herein may include progesterone, its salt, or its derivative.

[0071] In certain cases, the hormone may not be a steroid hormone, but instead may be a peptide hormone that is an agonist of a peptide hormone receptor. GLP-1 receptor agonists

[0072] In certain cases, peptide hormone can be glucagon-like peptide 1 receptor agonist (GLP-1), GLP-1-RA, gastric inhibitory peptide receptor agonist, including incretin exenatide, lixisenatide, incretin albiglutide, liraglutide, dulaglutide, glargine, glimepiride, semaglutide, sitagliptin, tirzepatide, taspoglutide, efpeglenatide, pharmaceutically acceptable salts thereof, derivatives thereof, or combinations thereof.Agonist can bind to GLP-1 receptor.This interaction can be used to treat diabetes, for example, type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), prediabetes, gestational diabetes, obesity, or combinations thereof. In certain cases, the treatment of the object of one of these agonists can be used for the object of coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or combinations thereof.In some cases, GLP-1 agonist can be used to treat dementia.In some cases, dementia can include Alzheimer's disease, vascular dementia, Lewy body disease, frontotemporal dementia, alcohol-related dementia, early-onset dementia, mild cognitive impairment, or any combinations thereof.

[0073] In some cases, the compositions herein may comprise a polypeptide of Table 1, such as any one of SEQ ID NOS: 1-12, a salt of any of these, or any combination thereof. In certain cases, the compositions herein are greater than 60% or 60% identical, greater than 65% or 65% identical, greater than 70% or 70% identical, greater than 75% or 75% identical, greater than 76% or 76% identical, greater than 77% or 77% identical, greater than 78% or 78% identical, greater than 79% or 79% identical, greater than 80% or 80% identical, greater than 81% or 81% identical, greater than 82% or 82% identical, greater than 83% or 83% identical, greater than 84% or 84% identical, or greater than 85% or 85% identical to any one of SEQ ID NOS: 1-12. , greater than 86% or 86% identical, greater than 87% or 87% identical, greater than 88% or 88% identical, greater than 89% or 89% identical, greater than 90% or 90% identical, greater than 91% or 91% identical, greater than 92% or 92% identical, greater than 93% or 93% identical, greater than 94% or 94% identical, greater than 95% or 95% identical, greater than 96% or 96% identical, greater than 97% or 97% identical, greater than 98% or 98% identical, or greater than 99% or 99% identical, or a salt of any of these. An incretin known as a gastric inhibitory polypeptide may comprise the polypeptide sequence of SEQ ID NO: 1. In certain cases, the sequence may be about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 listed in Table 1.

[0074] The liraglutide can comprise the polypeptide sequence of SEQ ID NO: 2. In certain cases, the liraglutide can be 100 percent identical to SEQ ID NO: 2. In certain cases, the sequence can be about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2 listed in Table 1.

[0075] Exenatide can comprise the polypeptide sequence of SEQ ID NO: 3. In certain cases, the exenatide can be 100 percent identical to SEQ ID NO: 3. In certain cases, the sequence can be about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3 listed in Table 1.

[0076] Lixisenatide can comprise the polypeptide sequence of SEQ ID NO: 4. In certain cases, lixisenatide can be 100 percent identical to SEQ ID NO: 4. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4 listed in Table 1.

[0077] Albiglutide may comprise the polypeptide sequence of SEQ ID NO: 5. In certain cases, the albiglutide may be 100 percent identical to SEQ ID NO: 5. In certain cases, the sequence may be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5 listed in Table 1.

[0078] Dulaglutide is a recombinant DNA polypeptide analog of GLP-1 covalently linked to each Fc arm of a human immunoglobulin. One chain of dulaglutide can comprise the polypeptide sequence of SEQ ID NO: 6. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6 listed in Table 1.

[0079] Taspoglutide can comprise the polypeptide sequence of SEQ ID NO: 7. In certain cases, the taspoglutide can be 100 percent identical to SEQ ID NO: 7. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7 listed in Table 1.

[0080] The GLP-1 receptor agonist can comprise the polypeptide sequence of SEQ ID NO: 12. In certain cases, the GLP-1 receptor antagonist can be 100 percent identical to SEQ ID NO: 12. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12 listed in Table 1. Growth hormone receptor agonists

[0081] In certain cases, human growth hormone receptor agonists, including human growth hormone peptides, salts, derivatives, or combinations thereof, can be used alone or as pharmaceutical preparations to treat conditions.In some cases, conditions may include a deficiency of human growth hormone.In certain cases, the human growth hormone receptor agonist can be somatotropin, somatropin, human chorionic somatomammotropin, derivatives thereof, salts thereof, or combinations thereof.In certain other cases, human growth hormone is derived from a human growth hormone stimulator.These can include, but are not limited to, somatocrinin, ghrelin, clonidine, α4β2 nicotinic agonist, glucagon, niacin, salts thereof, derivatives thereof, or combinations thereof. In certain instances, a human growth hormone receptor agonist or a promoter of a human growth hormone receptor agonist can be used to increase calcium retention, promote muscle mass gain, promote lipolysis, promote visceral growth, reduce hepatic glucose uptake, promote hepatic gluconeogenesis, promote pancreatic islet maintenance and function, stimulate the immune system, improve cognitive function, treat Turner syndrome, treat chronic renal failure, treat Prader-Willi syndrome, treat intrauterine growth restriction, treat severe idiopathic short stature, maintain muscle mass against muscle wasting in subjects with AIDS, promote anti-aging, increase lean body mass, promote the maintenance or increase of body density, treat multiple sclerosis, promote weight loss, treat fibromyalgia, treat heart failure, treat Crohn's disease, treat ulcerative colitis, and treat burns.

[0082] The human growth hormone can comprise the polypeptide sequence of SEQ ID NO: 8. In certain cases, the sequence can be 100 percent identical to SEQ ID NO: 8. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8 listed in Table 1.

[0083] The somatotropin can comprise the peptide sequence of SEQ ID NO: 9. In certain cases, the sequence of the somatotropin can be 100 percent identical to SEQ ID NO: 9. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9 listed in Table 1.

[0084] The somatropin can comprise the peptide sequence of SEQ ID NO: 10. In certain cases, the sequence of the somatropin can be 100 percent identical to SEQ ID NO: 10. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10 listed in Table 1.

[0085] Human chorionic somatomammotropin can include the peptide sequence of SEQ ID NO: 11. In certain cases, the sequence of human chorionic somatomammotropin can be 100 percent identical to SEQ ID NO: 11. In certain cases, the sequence can be at least about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11 listed in Table 1. [Table 1-1] [Table 1-2] [Table 1-3]

[0086] In certain cases, steroid hormone receptor agonist or its pharmaceutically acceptable salt can be used to treat depression, obesity, low libido, underdevelopment of muscle mass, underdevelopment of secondary sexual characteristics, depression, underdevelopment of body hair, underdevelopment of voice change, underdevelopment of tendon and ligament and spermatogenesis.In certain cases, these agonist or its pharmaceutically acceptable salt can be used to treat the condition characterized by low estrogen level, such as the regulation of female reproductive system, the lack of secondary sexual characteristics of female, reduced vaginal secretion, uterine hypoplasia, unnecessary bone resorption, insufficient bone formation, undesirably low body fat, thinning of vaginal wall, infertility, ovulation regulation, menstrual regulation, endometriosis, depression, obsessive-compulsive disorder, eating disorder and the low libido that can be seen in both men and women. In certain cases, these agonists or their pharmaceutically acceptable salts thereof can be used to treat conditions characterized by low progesterone levels, such as uterine cancer, cervical cancer, inability to prevent or maintain pregnancy, unwanted premature birth, unwanted lactation during pregnancy, inadequate breast development for breastfeeding, skin aging, libido regulation, etc.

[0087] In certain cases, the pharmaceutical compositions presented herein may relate to pharmaceutical compositions comprising a steroid receptor agonist or a pharmaceutical salt thereof that increases muscle mass.

[0088] In some cases, steroid hormone agonist or its salt or metformin or its salt can be administered orally or by capsule or capsule-in-capsule.In some cases, capsule can release pharmaceutical composition for nasal administration or inhalation administration by using inhaler.In some cases, steroid hormone agonist or its salt or metformin or its salt can be administered by food or drink as multi-layered microencapsulated particles.In some cases, steroid hormone agonist or its salt or metformin or its salt can be contained in gummy candy and can be administered as gummy candy.

[0089] In some embodiments, the composition may further comprise another set of active pharmaceutical ingredients or salts thereof, such as a second, third, or fourth set of different active pharmaceutical ingredients. In some embodiments, the additional pharmaceutical ingredients or salts thereof may be administered in parallel or sequentially to enhance the effectiveness of the first set of active pharmaceutical ingredients or salts. Combination Therapy

[0090] In some embodiments, the composition can further comprise a set of additional active ingredients or their salts, which can be administered in parallel or sequentially to enhance the effectiveness of hormone receptor agonists.In some embodiments, a second different active ingredient or a set of salts can be administered in parallel or sequentially to enhance the effectiveness of steroid receptor agonists.In some embodiments, the composition can comprise two or more different active ingredients or their salts, which can be administered in parallel or sequentially to enhance the effectiveness of hormone receptor agonists.

[0091] In some cases, the first therapeutic agent is a steroid receptor agonist or a salt thereof and the second therapeutic agent is a cannabinoid. In some cases, the steroid receptor agonist is estrogen, progesterone, or a combination thereof and the second therapeutic agent is a cannabinoid.

[0092] In some cases, the first therapeutic agent is a GLP-1 receptor agonist or a salt thereof and the second therapeutic agent is a cannabinoid. In some cases, the first therapeutic agent is a growth hormone receptor agonist or a salt thereof and the second therapeutic agent is a cannabinoid.

[0093] In some embodiments, the first set of drug substances or their salts can be administered in parallel or sequentially with the second set of different drug substances. In some aspects, the second set of different drug substances or their salts can be not included in the powdered pharmaceutical composition. In some aspects, the second set of different drug substances or their salts that are not included in the powdered pharmaceutical composition can be administered simultaneously, concurrently, or sequentially with the first set of drug substances. cannabinoids

[0094] The term "cannabinoid" may refer to a chemical compound that exhibits direct or indirect activity at cannabinoid receptors. In some cases, the compositions herein may include a cannabinoid. In some cases, the cannabinoid may be included in a powdered pharmaceutical composition. In some cases, the cannabinoid may be at least partially encapsulated. In some cases, the cannabinoid may include a phytocannabinoid. In some cases, the cannabinoid may include an endocannabinoid. In some cases, the endocannabinoid may include anandamide (arachidonoylethanolamide) or 2-arachidonoylglycerol (2-AG). In some cases, the cannabinoid may be a full-spectrum cannabinoid. In some cases, the cannabinoid may be a broad-spectrum cannabinoid. Examples of cannabinoids include, but are not limited to, tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and cannabidiolic acid (CBDA). In some cases, the cannabinoid may include cannabielsoin (CBE), cannabiditran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone, cannabifuran, cannabiglendol, cannabilipsol, or cannabiditran. In some cases, the cannabinoid may include a cannabinoid in Table 2. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] Table 2-5 Table 2-6 Table 2-7 Table 2-8

[0095] Tetrahydrocannabinol is commonly referred to as "THC," isolate THC, or full spectrum THC, and can include tetrahydrocannabinol delta-7, tetrahydrocannabinol delta-8, tetrahydrocannabinol delta-9, tetrahydrocannabinol delta-11, tetrahydrocannabinol delta-10, tetrahydrocannabinol delta-13, tetrahydrocannabivarin (THCV), and tetrahydrocannabinolic acid (THCA). In some cases, THC can include trans-THC, cis-THC, or both. In some cases, THC can exist as stereoisomers, such as (+)-trans-THC; (-)-trans-THC; (+)-cis-THC, and (-)-cis-THC. In some cases, cis-THC can include (+)-cis-THC, (-)-cis-THC, or both. In some cases, the trans-THC may include (+)-trans-THC, (-)-trans-THC, or both. In some cases, the composition may include trans-THC to cis-THC in a weight to weight ratio of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000. In some cases, the composition may include cis-THC to trans-THC in a weight to weight ratio of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000. In some cases, CBD may include trans-CBD. In some cases, trans-CBD may include (+)-trans-CBD, (-)-trans-CBD, or both. In some cases, CBD may include enantiomers or diastereomers. In some cases, CBD may include a racemate. In some cases, CBD may include trans-CBD, cis-CBD, or both. In some cases, CBD may include (1R,6R)-CBD, (1R,6S)-CBD, (1S,6R)-CBD, (1S,6S)-CBD, or a combination thereof.In some cases, the composition may include trans-CBD and cis-CBD in a weight-to-weight ratio of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000. In some cases, the composition may include cis-CBD and trans-CBD in a weight-to-weight ratio of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000. In some cases, the CBD may be in the form of a powder, liquid, oil, emulsion, aerosol, solid, or a combination thereof. In some cases, the CBD may be at least partially water-soluble. In some cases, the cannabinoid may be racemic. In some cases, the cannabinoid may include isomers. In some cases, the cannabinoid may include enantiomers or diastereomers. In some cases, the composition may include THC and CBD in a ratio (weight to weight) of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000. In some cases, the composition may include CBD and THC in a ratio (weight to weight) of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000. In some cases, CBD can be mixed with Δ8-THC, Δ9-THC, Δ10-THC, or combinations thereof in the composition. In some cases, the composition may include a ratio (weight to weight) of Δ8-THC, Δ9-THC, or Δ10-THC to CBD of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000.In some cases, the composition may include CBD and Δ8-THC, Δ9-THC, or Δ10-THC in a ratio (weight to weight) of about 1:1 to about 1:5, 1:4 to about 1:15, 1:10 to about 1:30, 1:20 to about 1:60, 1:40 to about 1:80, 1:75 to about 1:150, or about 1:100 to about 1:1000. In some cases, the cannabinoid or salt thereof may be derived from cannabis. In some cases, the cannabinoid or salt thereof may be derived from cannabis. In some cases, the tetrahydrocannabinol or salt thereof may be derived from cannabis. In some cases, the tetrahydrocannabinol delta-8 or salt thereof may be derived from cannabis. In some cases, the cannabinoid may be a synthetic cannabinoid or salt thereof. In some cases, the cannabinoid may include a derivative of a cannabinoid or a salt thereof. In some cases, the cannabinoid may include an isomer of a cannabinoid.

[0096] In some embodiments, the drug substance or salt thereof may comprise THC, CBD, a pharmaceutically acceptable salt of either of these, or any combination thereof. In some embodiments, the drug substance may be THC or a pharmaceutically acceptable salt thereof. Nonsteroidal anti-inflammatory drugs (NSAIDs)

[0097] In some embodiments, the additional active ingredient can comprise an NSAID or its salt, and the NSAID can comprise aspirin, ibuprofen, naproxen, diflunisal, dexibuprofen, oxaprozin, fenoprofen, indomethacin, tolmetin, celecoxib, clonixin, ketoprofen, any pharmaceutically acceptable salt thereof, or any combination thereof.In some cases, the composition herein can comprise an NSAID.In some cases, the NSAID can be included in a powdered pharmaceutical composition.In some cases, the NSAID can be at least partially encapsulated. Phosphodiesterase inhibitors

[0098] In some embodiments, the drug substance may include a phosphodiesterase inhibitor or a pharmaceutically acceptable salt thereof. In some cases, the phosphodiesterase inhibitor may be included in a powdered pharmaceutical composition. In some cases, the phosphodiesterase inhibitor may be at least partially encapsulated. In some cases, the additional active ingredient may include a phosphodiesterase inhibitor. In some embodiments, the phosphodiesterase inhibitor may be a phosphodiesterase type 5 inhibitor (PDE5 inhibitor). In some embodiments, the phosphodiesterase type 5 inhibitor may include sildenafil citrate (Viagra), tadalafil (Cialis), avanafil (Stendra), and vardenafil hydrochloride (Levitra). In some cases, the PDE-V inhibitor may include sildenafil, tadalafil, avanafil, vardenafil, esters thereof, salts thereof, or any combination thereof. In some cases, the PDE-V inhibitor may include mirodenafil, udenafil, lodenafil, zaprinast, icariin, any ester thereof, any pharmaceutically acceptable salt thereof, or any combination thereof. In some cases, the PDE-V inhibitor may include lodenafil carbonate. In some cases, the phosphodiesterase inhibitor may include a selective phosphodiesterase inhibitor, a non-selective phosphodiesterase inhibitor, a PDE-I selective inhibitor, a PDE-II selective inhibitor (e.g., EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine)), a PDE-III selective inhibitor, a PDE-IV selective inhibitor, a PDE-V selective inhibitor, a PDE-VI selective inhibitor, a PDE-VII selective inhibitor, a PDE-IX selective inhibitor, a PDE-X selective inhibitor, a PDE-XI selective inhibitor, any pharmaceutically acceptable salt thereof, or any combination thereof.In some cases, the drug substance may include oxindole, inamrinone, anagrelide, cilostazol, mesembrenone, rolipram, ibudilast, roflumilast, apremilast, cisaborole, sildenafil, tadalafil, vardenafil, udenafil, avanafil, dipyridamole, quinazoline, paraxanthine, papaverine, a pharmaceutically acceptable salt of any of these, an ester of any of these, or any combination thereof. In some cases, a PDE5 inhibitor or a salt thereof, such as sildenafil or a salt thereof, can be administered as a composition comprising a cannabinoid as described herein.

[0099] In some cases, the drug substance or salt may include a promoter of nitric oxide synthesis, such as arginine, ascorbic acid, folic acid, tetrahydrobiopterin, a pharmaceutically acceptable salt of any of these, a derivative thereof, or a combination thereof. Other medications

[0100] In some cases, the drug substance or its salt may include an antidiabetic drug or its salt. In some cases, the antidiabetic drug may be included in a powdered pharmaceutical composition. In some cases, the antidiabetic drug may be at least partially encapsulated. In some cases, the antidiabetic drug is a sulfonylurea, such as tolbutamide, acetohexamide, glimepiride, glipizide, glyburide, glyclopyramide, gliquidone, tolazamide, chlorpropamide, or any combination thereof. In some cases, the antidiabetic drug is a glinide, such as repaglinide, nateglinide, or a combination thereof. In some cases, the antidiabetic drug is a biguanide, such as metformin, phenformin, buformin, or a combination thereof. In some cases, the antidiabetic drug is a thiazolidinedione, such as rosiglitazone, pioglitazone, troglitazone, lobeglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, balaglitazone, or any combination thereof. In some cases, the antidiabetic drug is an alpha-glucosidase inhibitor, such as miglitol, acarbose, voglibose, or any combination thereof. In some cases, the antidiabetic drug is a dipeptidyl peptidase-4 inhibitor, such as vildagliptin, sitagliptin, saxagliptin, linagliptin, alogliptin, septagliptin, teneligliptin, gemigliptin, or any combination thereof. In certain cases, the antidiabetic drug is a glycosuric, such as dapagliflozin, canagliflozin, empagliflozin, remogliflozin, or any combination thereof.

[0101] In some cases, the compositions herein may include metformin. In some embodiments, the drug substance or its salt may include metformin or its salt. In some cases, metformin may be in the form of a dry powder produced by the methods described herein (e.g., spray drying). In some cases, metformin particles may be at least partially encapsulated. For example, metformin particles may be at least partially encapsulated by one, two, three, or more layers of coating material. In some cases, the coating material may include trehalose, hydroxypropylmethylcellulose (HPMC), fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropylmethylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, phospholipids, or any combination thereof. In some cases, the coating material may include an enteric coating. In some cases, the enteric coating may include methyl methacrylate (MMA) or a salt thereof. In some cases, the enteric coating may include plant fibers, polymers, shellac, waxes, fatty acids, plastics, or combinations thereof. In some cases, the enteric coating may include methyl acrylate-methacrylic acid copolymer, cellulose acetate phthalate (CAP), cellulose acetate succinate, hydroxypropylmethylcellulose phthalate, HPMCAS, polyvinyl acetate phthalate (PVAP), methyl methacrylate-methacrylic acid copolymer, shellac, cellulose acetate trimellitate, sodium alginate, zein, enteric coating solution (ethyl cellulose, medium chain triglyceride, oleic acid, sodium alginate, stearic acid), or combinations thereof. In some cases, excipients, carriers, and / or diluents can be added to compositions comprising at least partially encapsulated metformin particles.

[0102] In some cases, at least partially encapsulated metformin particles can be added to a gummy can. In some cases, the at least partially encapsulated metformin particles can have a particle size ranging from about 1 micrometer to 200 micrometers, or a plurality of metformin particles can have a mean or median particle size of about 1 micrometer to about 200 micrometers, as measured by a particle analyzer using laser diffraction. In some cases, the at least partially encapsulated metformin particles are less than about 1 μm, greater than or equal to 1 μm, less than 5 μm, greater than or equal to 5 μm, less than 10 μm, greater than or equal to 10 μm, less than 20 μm, greater than or equal to 20 μm, less than 30 μm, greater than or equal to 30 μm, less than 40 μm, greater than or equal to 40 μm, less than 50 μm, greater than or equal to 50 μm, less than 60 μm, greater than or equal to 60 μm, less than 70 μm, greater than or equal to 70 μm, less than 80 μm, greater than or equal to 80 μm, less than 90 μm, greater than or equal to 90 μm, less than 100 μm, More than or equal to 100 μm, less than 110 μm, more than or equal to 110 μm, less than 120 μm, more than or equal to 120 μm, less than 130 μm, more than or equal to 130 μm, less than 140 μm, more than or equal to 140 μm, less than 150 μm, more than or equal to 150 μm The at least partially encapsulated metformin particles may have a particle size of less than 160 μm, less than 160 μm, more than or equal to 160 μm, less than 170 μm, more than or equal to 170 μm, less than 180 μm, more than or equal to 180 μm, less than 190 μm, more than or equal to 190 μm, or less than 200 μm, more than or equal to 200 μm. In some cases, the at least partially encapsulated metformin particles may be formulated to have any particle size disclosed herein. In some cases,A gummy containing at least partially encapsulated metformin particles can contain from about 10 mg to about 5,000 mg of metformin. In some cases, a gummy containing at least partially encapsulated metformin particles can contain from about greater than, less than, or equal to 10 mg, greater than, less than, or equal to 50 mg, greater than, less than, or equal to 100 mg, greater than, less than, or equal to 200 mg, greater than, less than, or equal to 300 mg, greater than, less than, or equal to 300 mg, greater than, less than, or equal to 400 mg, greater than, less than, or equal to 400 mg, greater than, 500 mg, or greater than 500 mg. Less than 0 mg or equal to 500 mg, More than 600 mg, Less than 600 mg or equal to 600 mg, More than 700 mg, Less than 700 mg or equal to 700 mg, More than 800 mg, Less than 800 mg or equal to 800 mg, More than 900 mg, Less than 900 mg or equal to 900 mg, More than 1000 mg, Less than 1000 mg or equal to 1000 mg, More than 1100 mg, Less than 1100 mg or equal to 1100 mg, More than 1200 mg, Less than 1200 mg Less than or equal to 1200 mg, More than 1300 mg, Less than 1300 mg or equal to 1300 mg, More than 1400 mg, Less than 1400 mg or equal to 1400 mg, More than 1500 mg, Less than 1500 mg or equal to 1500 mg, More than 1600 mg, Less than 1600 mg or equal to 1600 mg, More than 1700 mg, Less than 1700 mg or equal to 1700 mg, More than 1800 mg, Less than 1800 mg or equal to 1800 mg, More than 1900 mg less than or equal to 1900 mg; more than 2000 mg, less than 2000 mg, or equal to 2000 mg; more than 2100 mg, less than 2100 mg, or equal to 2100 mg; more than 2200 mg, less than 2200 mg, or equal to 2200 mg; more than 2300 mg, less than 2300 mg, or equal to 2300 mg; more than 2400 mg, less than 2400 mg, or equal to 2400 mg; more than 2500 mg, less than 2500 mg, or equal to 2500 mg;The metformin content may be greater than, less than, or equal to 2600 mg, greater than, less than, or equal to 2700 mg, greater than, less than, or equal to 2800 mg, greater than, less than, or equal to 2900 mg, or greater than, less than, or equal to 2900 mg, or greater than, less than, or equal to 3000 mg. In some cases, the gummy candy containing at least partially encapsulated metformin particles may contain about 100 mg to about 3000 mg; 500 mg to about 2500 mg; 100 mg to about 1000 mg, 500 mg to about 1500 mg, or about 100 mg to about 500 mg of metformin. In some cases, the gummy candy containing at least partially encapsulated metformin may be present in a kit. In some cases, the kit may include a container.

[0103] In some cases, the at least partially encapsulated metformin particles can be administered in the form of a drink or food (e.g., a gummy candy). In some embodiments, the gummy can provide at least a substantially controlled release of metformin or a salt thereof over time. In some cases, the gummy can provide a substantially immediate release of metformin or a salt thereof, for example, in the stomach or small intestine. In some cases, the at least partially encapsulated metformin particles can be used to treat a disease or condition. In some cases, the at least partially encapsulated metformin particles can be administered to a subject having a disease or condition. In some cases, the disease or condition can include type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), prediabetes, metabolic syndrome, gestational diabetes, polycystic ovary syndrome, obesity, weight gain due to antipsychotic medication, liver disease, cardiovascular disease, kidney disease, or any combination thereof. In some cases, the at least partially encapsulated metformin particles can be administered to a subject for lifespan extension, healthspan extension, or both. In some embodiments, the drug substance or salt may include an antibiotic, an antiviral, an antiparasitic, a diuretic, a beta-blocker, an ACE inhibitor, an angiotensin II receptor blocker, a calcium channel blocker, an alpha-blocker, a cancer chemotherapy drug, an anti-inflammatory steroid, an immunomodulator, a pharmaceutically acceptable salt of any of these, or any combination thereof. In some cases, the antibiotic may include a penicillin, a cephalosporin, a tetracycline, an aminoglycoside, a macrolide, a clindamycin, a sulfonamide, a trimethoprim, a metronidazole, a quinolone, or a nitrofurantoin. The antiviral drug may include acyclovir, peramivir, zanamivir, oseltamivir phosphate, remdesivir, baloxavir marboxil, a salt of any of these, or any combination thereof. In some cases, the drug substance or salt thereof may include a potassium channel blocker, such as dalfampridine or a salt thereof. In some cases, the drug substance or salt thereof may include levodopa, carbidopa, or a salt thereof.In some cases, the pharmaceutical ingredients may include beta blockers (β-blockers), calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, nebivolol, CYP3A4 inhibitors, ketoconazole (Nizoral), itraconazole (Sporanox), erythromycin, saquinavir, clarithromycin, HIV protease inhibitors, alpha-adrenergic blockers (α-blockers), salts thereof, or any combination thereof.

[0104] In some cases, the pharmaceutical ingredients may include nitrates, nitric oxide, nitric oxide-producing components, nitrites, nitrates, sodium nitrate, potassium nitrate, vitamin C, ascorbic acid, L-arginine, L-citrulline, vitamin B12, magnesium ascorbate, sodium ascorbate, potassium ascorbate, antihypertensive agents, diuretics, salts thereof, or any combination thereof.

[0105] In some aspects, pharmaceutical compositions have metabolites that may be pharmacologically active, which at least partially retain the efficacy of the parent drug or parent pharmaceutical component. salt

[0106] In some embodiments, the pharmaceutical composition comprises a salt of a pharmaceutically active ingredient, wherein the salt comprises an organic salt, an inorganic salt, or any combination thereof. In some cases, the organic salt may comprise a phosphinate (e.g., sodium hypophosphite), a hydrazinium salt, a urate, a diazonium salt, an oxalate, a tartrate, or choline chloride. Examples of inorganic salts may include sodium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, potassium chloride, sodium sulfate, calcium carbonate, calcium phosphate, or any combination thereof.

[0107] In certain embodiments, the salt comprises an HCl salt, an ascorbate salt, a mandelate salt, an aspartate salt, a carbonate salt, a citrate salt, a formate salt, a glutamate salt, a lactate salt, a laurate salt, a maleate salt, a borate salt, a bitartrate salt, a palmitate salt, a phosphate salt, or any combination thereof. In certain embodiments, pharmaceutically acceptable salts include, but are not limited to, metal salts such as sodium salts, potassium salts, cesium salts, and the like; alkaline earth metal salts such as calcium salts, magnesium salts, and the like; organic amine salts such as triethylamine salts, pyridine salts, picoline salts, ethanolamine salts, triethanolamine salts, dicyclohexylamine salts, N,N'-dibenzylethylenediamine salts, and the like; inorganic acid salts such as hydrochloride, hydrobromide, phosphate, sulfate, and the like; organic acid salts such as citrate, lactate, tartrate, maleate, fumarate, mandelate, acetate, dichloroacetate, trifluoroacetate, oxalate, formate, and the like; sulfonate salts such as methanesulfonate, benzenesulfonate, p-toluenesulfonate, and the like; and amino acid salts such as alginate, aspartate, glutamate, and the like. Excipients and other inactive ingredients

[0108] In some embodiments, pharmaceutical compositions may include pharmaceutically acceptable excipients, diluents, and / or carriers. As used herein, an excipient may refer to a substance formulated with an active ingredient of a drug for long-term stability, to add bulk to solid formulations containing small amounts of high-potency active ingredients, and / or to impart therapeutic enhancements to the active ingredient(s) in the final dosage form. In some cases, the diluent may include water or saline. In some cases, the carrier may include water, sugar solution, honey, or saline. Excipients can facilitate drug absorption, reduce viscosity, or enhance solubility. Excipients can also facilitate handling of the active ingredient, improve in vitro stability, and / or extend the shelf life of the pharmaceutical product. The choice of excipient may vary depending on the route of administration for drug delivery, the unit dose, and the active ingredients that comprise the composition.

[0109] In some embodiments, the excipient is calcium phosphate anhydrous, calcium phosphate dihydrate, hydroxypropyl methylcellulose, croscarmellose sodium, GMO-free croscarmellose sodium, carbomer, magnesium aluminum metasilicate, mannitol, povidone (PVP), crospovidone, sorbitol, dimethicone, sodium stearyl fumarate, sodium starch glycolate, hydroxypropyl cellulose, native corn starch, modified corn starch, carrageenan, alginate, silicon dioxide, microcrystalline cellulose, sodium carboxymethylcellulose, alginate, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (Na CMC), carbomer, natural gums, sorbitol, maltitol, glucose syrup, silicone, carbomer, fatty alcohol, alcohol, carbohydrate, petrolatum derivative, butter, wax, DMSO, ester, fatty acid, oil-in-water (O / W) emulsifier, water-in-oil (W / O) emulsifier, silica, fumed silica, polysorbate, isopropyl myristate, cellulosic derivatives, xanthan gum, propylene glycol, noveon AA-1 polycarbophil, dimethyl isosorbate, polysilicone elastomer 1100, polysilicone elastomer 1148P, preservatives, flavors, dyes, functional coatings, aesthetic coatings, pharmaceutically acceptable salts of any of these, or any combination thereof.

[0110] In some cases, the pharmaceutically acceptable excipient may be gum arabic, acesulfame potassium, glacial acetic acid, acetone, acetyl tributyl citrate, acetyl triethyl citrate, agar, albumin, alcohol, alginate, aliphatic polyester, alitame, almond oil, alpha tocopherol, aluminum hydroxide adjuvant, aluminum oxide, aluminum phosphate adjuvant, aluminum stearate, ammonia solution, ammonium alginate, ascorbic acid, ascorbyl palmitate, aspartame, attapulgite, Bentonite, benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, benzyl benzoate, boric acid, bronopol, butylated hydroxyanisole, butylated hydroxytoluene, butylparaben, calcium alginate, calcium carbonate, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate hydrate, basic calcium phosphate, calcium stearate, calcium sulfate, canola oil, carbomer, carbon dioxide, calcium carboxymethylcellulose, sodium carboxymethylcellulose, carrageenan, castor oil, Hydrogenated castor oil, cellulose (e.g., microcrystalline cellulose, powdered cellulose, silicified microcrystalline cellulose, cellulose acetate, cellulose acetate phthalate), ceratonia, cetostearyl alcohol, cetrimide, cetyl alcohol, cetylpyridinium chloride, chitosan, chlorhexidine, chlorobutanol, chlorocresol, chlorodifluoroethane, chlorofluorocarbons, chloroxylenol, cholesterol, citric acid monohydrate, colloidal silicon dioxide, coloring, copovidone, corn oil, cottonseed oil, cresol, croscarmellose sodium Sodium, crospovidone, cyclodextrin, cyclomethicone, denatonium benzoate, dextrates, dextrin, dextrose, dibutyl phthalate, dibutyl sebacate, diethanolamine, diethyl phthalate, difluoroethane, dimethicone, dimethyl ether, dimethyl phthalate, dimethyl sulfoxide, dimethylacetamide, edetate disodium, docusate sodium, edetic acid, erythorbic acid, erythritol, ethyl acetate, ethyl lactate, ethyl maltol, ethyl oleate, ethyl vanillin, ethyl celluloseEthylene glycol palmitostearate, ethylene vinyl acetate, ethylparaben, fructose, fumaric acid, gelatin, glucose, glycerin, glyceryl behenate, glyceryl monooleate, glyceryl monostearate, glycerin palmitate stearate, glycofurol, guar gum, hectorite, heptafluoropropane, hexetidine, hydrocarbons, hydrochloric acid, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl Pill starch, hypromellose, hypromellose acetate succinate, hypromellose phthalate, honey, imidurea, inulin, iron oxide, isomalt, isopropyl alcohol, isopropyl myristate, isopropyl palmitate, kaolin, lactic acid, lactitol, lactose anhydrous, lactose hydrate, spray-dried lactose, lanolin, lanolin alcohol, hydrolyzed lanolin, lauric acid, lecithin, leucine, linoleic acid, macrogol hydroxystearic acid, magnesium aluminum silicate, magnesium carbonate, magnesium oxide, magnesium silicate Sodium, magnesium stearate, magnesium trisilicate, malic acid, maltitol, maltitol liquid, maltodextrin, maltol, maltose, mannitol, medium chain triglycerides, meglumine, menthol, methylcellulose, methylparaben, mineral oil, mineral oil and lanolin alcohol, monoethanolamine, sodium glutamate, monothioglycerol, myristic acid, neohesperidin dihydrochalcone, nitrogen, nitrous oxide, octyldodecanol, oleic acid, oleyl alcohol, olive oil, palmitic acid, paraffin , peanut oil, pectin, petrolatum, petrolatum and lanolin alcohol, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, phosphoric acid, polacrilin potassium, poloxamer, polycarbophil, polydextrose, polyethylene glycol, polyethylene oxide, polymethacrylate, poly(methyl vinyl ether / maleic anhydride), polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters,Polyoxyethylene stearate, polyvinyl acetate phthalate, polyvinyl alcohol, potassium alginate, potassium benzoate, potassium bicarbonate, potassium chloride, potassium citrate, potassium hydroxide, potassium metabisulfite, potassium sorbate, povidone, propionic acid, propyl gallate, propylene carbonate, propylene glycol, propylene glycol alginate, propylparaben, 2-pyrrolidone, raffinose, saccharin, saccharin sodium, saponite, sesame oil, shellac, simethicone, sodium acetate, sodium alginate, sodium ascorbate, sodium benzoate, sodium bicarbonate, sodium borate, sodium chloride, sodium citrate dihydrate, sodium cyclamate, sodium hyaluronate, sodium hydroxide, sodium lactate, sodium lauryl sulfate, sodium metabisulfite, sodium hydrogen phosphate hydrate, sodium dihydrogen phosphate anhydrous, sodium propionate, starch glycol Sodium stearate, sodium stearyl fumarate, sodium sulfite, sorbic acid, sorbitan esters (sorbitan fatty acid esters), sorbitol, soybean oil, starch, starch (e.g., pregelatinized starch, sterilizable corn starch), stearic acid, stearyl alcohol, sucralose, sucrose, compressible sugar, powdered sugar, granulated sugar, sulfobutyl ether b-cyclodextrin, sulfuric acid, sunflower oil, suppository base, hard fat, talc, tartaric acid, tetrafluoroethylene The composition may include thaumatin, thimerosal, thymol, titanium dioxide, tragacanth, trehalose, triacetin, tributyl citrate, triethanolamine, triethyl citrate, vanillin, hydrogenated vegetable oil, water, anionic emulsifying wax, wax (e.g., carnauba wax, cetyl esters, microcrystalline wax, nonionic emulsifying wax, white wax, yellow wax), xanthan gum, xylitol, zein, zinc acetate, zinc stearate, or any combination thereof.

[0111] In some aspects, the pharmaceutically acceptable excipient may include carbohydrates, alginates, povidone, carbomers, flavorings, natural gums, silicones, alcohols, butters, waxes, fatty acids, preservatives, pharmaceutically acceptable salts of any of these, or any combination thereof. In some aspects, the pharmaceutically acceptable excipient may include carbohydrates. In some cases, the carbohydrate may include lactose, microcrystalline cellulose, cellulose, mannitol, sorbitol, starch, starch glycolate, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, cyclodextrin, maltodextrin, trehalose, croscarmellose sodium, corn starch, carrageenan, sorbitol, maltitol, glucose, pharmaceutically acceptable salts of any of these, or any combination thereof. In some aspects, the pharmaceutically acceptable excipient may include lactose. In some cases, the lactose may include milled lactose, sieved lactose, micronized lactose, spray-dried lactose, at least substantially anhydrous lactose, lactose monohydrate, or a combination thereof. In some cases, the excipient may include fumaryl diketopiperazine (FDKP). In some cases, the excipient may include 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).

[0112] In some embodiments, the dosage, such as an inhalable dosage, is in a lipid formulation. In certain cases, the liposome may be a positively charged liposome. In certain cases, the liposome may be a negatively charged liposome. In certain cases, the lipid may be a saturated phospholipid, such as dipalmitoylphosphatidylcholine (DPPC). In certain cases, the lipid may be a glycerophospholipid. The glycerophospholipid may be phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylglycerol (PG), cardiolipin (CL), or any combination thereof. In certain instances, the lipid is a phospholipid, such as soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), egg sphingomyelin (ESM), egg phosphatidylcholine (EPC), dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidylcholine (DPPC), dipalmito ...palmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylcholine (DOPC), distearoylphosphatidylcholine (DSPC), dipalmitoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylcholine The phosphatidylglycerol may be dimyristoylphosphatidylglycerol (DPPG), dioleoylphosphatidylglycerol (DOPG), distearoylphosphatidylglycerol (DSPG), dimyristoylphosphatidylethanolamine (DMPE), dipalmitoylphosphatidylethanolamine (DPPE), dioleoylphosphatidylethanolamine (DOPE), dimyristoylphosphatidylserine (DMPS), dipalmitoylphosphatidylserine (DPPS), or any combination thereof.

[0113] In some embodiments, the active ingredient or its pharmaceutically acceptable salt may be at least partially contained within the excipient. In some embodiments, the active ingredient or its pharmaceutically acceptable salt may be at least partially contained in the excipient. In some embodiments, the active ingredient may be contained within the pores of the excipient. The "pores" of the excipient may refer to excipient particles engineered to have an open or closed pore structure. Porous excipient particles may be carriers for pharmaceutical active ingredients. Porous excipient particles may have a large surface area, a stable structure, adjustable pore size, adjustable dissolution, diffusion, or distribution, and well-defined surface properties. Porous excipient particles may facilitate sustained-release unit doses.

[0114] In some embodiments, the composition may further comprise, in addition to the drug substance or its salt, an inactive ingredient selected from the group consisting of microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, lactose, triacetin, mannitol, xylitol, sorbitol, sugar alcohol, cellulose, cellulose ester, cellulose ether, modified cellulose, starch, modified starch, polysaccharides, oligosaccharides, disaccharides, sugars, gelatin, polyvinylpyrrolidone, polyethylene glycol, binders, flavors, colorants, FD&C Blue #2 aluminum lake, magnesium stearate, anti-adherents, stearates, sweeteners, silica, lubricants, or any combination thereof. Inhalable formulations

[0115] Advances in engineering and process automation enable enhanced manufacturing methods to achieve consistent active ingredient particle sizes between 1.0 and 10.0 micrometers, which contribute to adequate pulmonary absorption. Drugs can be processed using spray drying techniques to control particle size and particle size distribution. Spray drying can result in active ingredient particle sizes in the 1.0 to 10.0 micrometer range. This particle size may be necessary when administering drugs via inhalation or intranasal routes for absorption into the alveoli. In some cases, particles can be microencapsulated to enhance bioavailability. This route of administration can result in rapid entry of the drug into the bloodstream, reducing the required dose compared to oral ingestion of capsules or tablets. In some cases, introducing an encapsulated hormone receptor agonist into the lungs via inhalation can allow the hormone receptor agonist to reach the bloodstream within five minutes.

[0116] In some embodiments, the composition may include one or more of an active ingredient or its salt, an excipient, and an inactive ingredient. In some cases, the pharmaceutical composition may include particles. In some cases, the particles may include an excipient (e.g., a pharmaceutically acceptable excipient), an active ingredient, an encapsulated active ingredient, or any combination thereof. In some cases, the composition may include a pharmaceutical composition. In some cases, the composition may include particles of a pharmaceutically acceptable excipient. In some cases, the composition may include particles of an active ingredient.

[0117] As used herein, "coating material" may refer to a material added by a pharmaceutical coating process, which can apply an essentially dry outer layer of coating material to the surface of a dosage form. Dosage form coatings can be used to improve stability (protection from light, moisture and gas barrier), facilitate administration, or modify the drug release behavior from the dosage form. Coating materials can be used to enable immediate drug release, delayed drug release (e.g., as with enteric coatings), or prolonged drug release from the dosage form. Coating materials can include film coating formulations, which typically contain polymers, plasticizers, colorants, opacifiers, solvents, and vehicles. In some cases, coating materials can refer to coating materials used to coat particles of active ingredients to create encapsulated particles.

[0118] In some embodiments, the composition may comprise a mixture of particles as described herein. In some embodiments, the particles may be mixed to form a substantially uniform mixture. In some cases, at least a portion of the pharmaceutically acceptable excipient particles may have a particle size ranging from about 50 micrometers to about 200 micrometers, as measured by a particle size analyzer using laser diffraction. In some cases, at least a portion of the active ingredient particles may have a particle size ranging from about 500 nanometers to about 15 micrometers, or from about 1 micrometer to about 20 micrometers, as measured by a particle size analyzer using laser diffraction. In some cases, in human clinical trials, the time to peak plasma concentration (Tmax) of the active ingredient or its salt when the powdered pharmaceutical composition is inhaled into the lungs may range from about 1 minute to about 1 hour, or from about 1 minute to about 10 minutes, in at least some of the humans in the clinical trials. In some embodiments, the Tmax of the active ingredient or salt thereof is from about 1 minute to about 5 minutes, from about 1 minute to about 10 minutes, from about 1 minute to about 20 minutes, from about 1 minute to about 25 minutes, from about 1 minute to about 30 minutes, from about 1 minute to about 40 minutes, from about 1 minute to about 50 minutes, from about 1 minute to about 60 minutes, from about 5 minutes to about 10 minutes, from about 5 minutes to about 20 minutes, from about 5 minutes to about 25 minutes, from about 5 minutes to about 30 minutes, from about 5 minutes to about 40 minutes, from about 5 minutes to about 50 minutes, from about 5 minutes to about 60 minutes, from about 10 minutes to about 20 minutes, from about 10 minutes to about 25 minutes, from about 10 minutes to about 30 minutes. , from about 10 minutes to about 40 minutes, from about 10 minutes to about 50 minutes, from about 10 minutes to about 60 minutes, from about 20 minutes to about 25 minutes, from about 20 minutes to about 30 minutes, from about 20 minutes to about 40 minutes, from about 20 minutes to about 50 minutes, from about 20 minutes to about 60 minutes, from about 25 minutes to about 30 minutes, from about 25 minutes to about 40 minutes, from about 25 minutes to about 50 minutes, from about 25 minutes to about 60 minutes, from about 30 minutes to about 40 minutes, from about 30 minutes to about 50 minutes, from about 30 minutes to about 60 minutes, from about 40 minutes to about 50 minutes, from about 40 minutes to about 60 minutes, or from about 50 minutes to about 60 minutes.

[0119] In some aspects, in human clinical trials, the powdered pharmaceutical composition functions mechanistically such that, when inhaled into the lungs, the majority of particles of the pharmaceutically acceptable excipient are deposited on the oropharynx in at least a portion of the humans in the clinical trials.

[0120] In some embodiments, the weight ratio of a) particles of pharmaceutically acceptable excipient to b) particles of active ingredient ranges from about 1:1 to about 10,000:1. In some embodiments, the weight ratio of a) particles of pharmaceutically acceptable excipient to b) particles of active ingredient ranges from about 1:1 to about 20:1, from about 1:1 to about 15:1, from about 1:1 to about 10:1, from about 1:1 to about 5:1, from about 1:1 to about 2:1, from about 2:1 to about 20:1, from about 2:1 to about 15:1, from about 2:1 to about 10:1, from about 2:1 to about 5:1, from about 5:1 to about 20:1, from about 5:1 to about 15:1, from about 5:1 to about 10:1, from about 10:1 to about 15:1, from about 10:1 to about 20:1, from about 15:1 to about 20:1, from about 18:1 to about 25:1, or from about 25:1 to about 30:1. In some embodiments, the weight ratio of a) particles of pharmaceutically acceptable excipient to b) particles of active ingredient can be about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, or 30:1. In some embodiments, the weight ratio of a) particles of pharmaceutically acceptable excipient to b) particles of active ingredient ranges from about 1:1 to about 1:10, from about 1:1 to about 1:8, from about 1:1 to about 1:5, from about 1:1 to about 1:2, from about 1:2 to about 1:10, from about 1:2 to about 1:8, from about 1:2 to about 1:5, from about 1:5 to about 1:10, from about 1:5 to about 1:8, from about 1:8 to about 1:10.

[0121] In some embodiments, at least a portion of the particles of pharmaceutical excipient and the particles of active ingredient may not be covalently bonded to one another.

[0122] In some embodiments, the solid active ingredient is spherical or substantially spherical and not encapsulated. In other cases, the solid active ingredient is spherical or substantially spherical and encapsulated. In certain cases, the spherical or substantially spherical active ingredient is mixed with an excipient. In certain cases, the excipient may also be spherical or substantially spherical. In certain cases, the excipient may include lactose, microcrystalline cellulose, cellulose, mannitol, sorbitol, starch, starch glycolate, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, cyclodextrin, maltodextrin, croscarmellose sodium, corn starch, carrageenan, sorbitol, maltitol, glucose, fumaryl diketopiperazine (FDKP), a pharmaceutically acceptable salt of any of these, or any combination thereof. Oral administration formulation

[0123] Disclosed herein are devices, systems, and methods for preparing, encapsulating, and orally delivering stable powder compositions. In some cases, the microencapsulated particles may contain multiple coatings and can be administered by inhalation. In some cases, the microencapsulated particles may contain multiple coatings and can be orally administered. For example, microencapsulated particles with one or more coatings (e.g., shells) can be added to a liquid and administered orally. In some embodiments, the microencapsulated particles can be configured (e.g., using one or more layers of enteric coating) to at least partially release the active ingredient in the mouth, esophagus, small intestine, duodenum, jejunum, ileum, cecum, colon, ascending colon, transverse colon, descending colon, sigmoid colon, rectum, anus, or any combination thereof. In some cases, the microencapsulated particles can be added to a capsule, such as a capsule-in-capsule composition, and administered orally.

[0124] In some embodiments, the composition can be spray-dried. In some embodiments, the spray-dried powder can be processed through a fluidized bed to apply a polymer barrier or enteric coating. In some embodiments, the composition can include one or more coatings. For example, microencapsulated particles can have one, two, three, four, five, or more than five coatings made of the same or different coating materials. Overall, the spray-dried particles can individually have a particle size ranging from about 20 micrometers to about 200 micrometers, or have an average or median particle size of about 20 micrometers to about 200 micrometers, as measured by a particle analyzer using laser diffraction.

[0125] The first coating may include trehalose. In certain cases, the first coating may include trehalose and hydroxypropyl methylcellulose acetate succinate (HPMCAS). In other cases, the first coating material may include cyclodextrin, maltodextrin, povidone, copovidone, or any combination thereof. In certain cases, the first coating may further include a cannabinoid or a pharmaceutically acceptable salt thereof. In some cases, the first coating may include hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cyclodextrin, maltodextrin, povidone, copovidone, or any combination thereof. In some cases, the first coating may include any wall or shell material.

[0126] In some cases, the first coating can be substantially encapsulated by one or more enteric coatings. An enteric coating comprises a barrier, such as a polymer barrier, that can be applied to a composition (e.g., a microencapsulated particle) to prevent dissolution or disintegration in the stomach. In some cases, this allows the active ingredient to bypass the stomach and enter the small intestine before the active ingredient is released. In some cases, the wall material, for example, an additional coating on an already microencapsulated particle, can comprise an enteric coating. In some cases, the first coating of a microencapsulated particle can comprise an enteric coating. In some cases, the enteric coating can comprise methyl methacrylate (MMA). In some cases, the enteric coating can comprise plant fiber, shellac, wax, fatty acid, plastic, or a combination thereof. In some cases, the enteric coating may include methyl acrylate-methacrylic acid copolymer, cellulose acetate phthalate (CAP), cellulose acetate succinate, hydroxypropyl methylcellulose phthalate, HPMCAS, polyvinyl acetate phthalate (PVAP), methyl methacrylate-methacrylic acid copolymer, shellac, cellulose acetate trimellitate, sodium alginate, zein, enteric coating solution (ethyl cellulose, medium chain triglycerides, oleic acid, sodium alginate, stearic acid), or combinations thereof.

[0127] In some cases, the wall material coating may include an enteric coating, a time-release coating, a pH-dependent coating, a delayed-release coating, an extended-release coating, or a combination thereof. The wall material may be biodegradable and biocompatible with the pharmaceutical ingredient. In some cases, the wall material may be biodegradable and biocompatible with the already applied wall material.

[0128] In some cases, microcapsules can be made by dissolving, dispersing, or mixing a pharmaceutical ingredient in a solvent containing a shell material to form a liquid suspension. In some cases, multiply coated microcapsules can be made by dissolving, dispersing, or mixing an already microencapsulated pharmaceutical ingredient in a solvent containing a second shell material to form a liquid suspension. For example, HPMCAS can be dissolved in ethanol and water, and a pharmaceutical compound (e.g., a core) can be added to the liquid suspension. In another example, an active ingredient encapsulated by HPMCAS can be dispersed in water, and an enteric shell can be added to the liquid suspension. In some cases, the pharmaceutical compound may not dissolve in the liquid suspension. In some cases, the pharmaceutical compound may dissolve in the liquid suspension. In some cases, the encapsulated particles may not dissolve in the liquid suspension. In some cases, the encapsulated particles may dissolve in the liquid suspension. The liquid suspension can be dried using the spray drying techniques described herein or by another method.

[0129] To prevent dissolution of the active ingredients described herein until they have passed through the stomach, one or more layers of enteric coating can be applied to the active ingredients described herein via the microencapsulation process and / or flow system described herein. In some cases, two or more enteric coatings can be applied to the active ingredient. In some cases, the microencapsulated particle coating can release the active ingredient depending on the pH value in the gastrointestinal (GI) tract. The GI tract can have different pH values, thereby enabling pH-dependent dosing in specific regions. For example, the pH of the stomach (an acidic pH of approximately 1.5 to 4.0) differs from the pH of the small intestine (pH 4.0 to 7.0), and pH-microencapsulated particle coatings can be used to deliver medication to regions of the GI tract with specific pH levels. In some embodiments, the enteric coating of the microencapsulated particles can be a polymer barrier that can be applied to the microencapsulated particles described herein to enable controlled release. Bypassing the stomach can allow for more precise dosing and can also enable greater bioavailability of the drug in the gastrointestinal tract. In some cases, these coatings or multiple layers of these coatings can be modified to allow drugs to be delivered from the mouth all the way to the colon.In some cases, this technology can be applied to different microencapsulated layers of active ingredient particles, and can achieve intended drug delivery by utilizing timed release, pH-controlled release, or a combination of both technologies.In some cases, one or more layers of the microcapsule shell can increase or decrease the active ingredient release kinetics.In some cases, one or more layers of the microcapsule shell can increase or decrease bioavailability.In some cases, microencapsulation of an active ingredient disclosed herein, e.g., testosterone or a pharmaceutically acceptable salt thereof, when ingested by a subject can result in about 5% to about 70%, 5% to about 10%, 5% to about 20%, 10% to about 30%, 15% to about 40%, 25% to about 40%, 10% to about 60%, or 20% to about 50% greater bioavailability of the active ingredient or a salt thereof compared to the unencapsulated active ingredient or a salt thereof.

[0130] With respect to the thickness of an individual coating of a microencapsulated particle, the thickness may be greater than, less than, or equal to about 500 nm, greater than, less than, or equal to 550 nm, greater than, less than, or equal to 550 nm, greater than, less than, or equal to 600 nm, greater than, less than, or equal to 650 nm, greater than, less than, or equal to 700 nm, greater than, less than, or equal to 700 nm, greater than, less than, or equal to 750 nm, greater than, less than, or equal to 750 nm, greater than, less than, or equal to 800 nm, or or equal to 800 nm, greater than 850 nm, less than 850 nm, or equal to 850 nm, greater than 900 nm, less than 900 nm, or equal to 900 nm, greater than 950 nm, less than 950 nm, or equal to 950 nm, greater than 1 μm, less than 1 μm, or equal to 1 μm, greater than 2 μm, less than 2 μm, or equal to 2 μm, greater than 3 μm, less than 3 μm, or equal to 3 μm, greater than 4 μm, less than 4 μm, or equal to 4 μm, greater than 5 μm, less than 5 μm, or equal to 5 μm, greater than 6 μm, 6 μm Less than or equal to 6 μm, Greater than 7 μm, Less than 7 μm or equal to 7 μm, Greater than 8 μm, Less than 8 μm or equal to 8 μm, Greater than 9 μm, Less than 9 μm or equal to 9 μm, Greater than 10 μm, Less than 10 μm or equal to 10 μm, Greater than 11 μm, Less than 11 μm or equal to 11 μm, Greater than 12 μm, Less than 12 μm or equal to 12 μm, Greater than 13 μm, Less than 13 μm or equal to 13 μm, Greater than 14 μm, Less than 14 μm or equal to 14 μm, Greater than 15 μm, 15 less than μm or equal to 15 μm, greater than 16 μm, less than 16 μm or equal to 16 μm, greater than 17 μm, less than 17 μm or equal to 17 μm, greater than 18 μm, less than 18 μm or equal to 18 μm, greater than 19 μm, less than 19 μm or equal to 19 μm, greater than 20 μm, less than 20 μm or equal to 20 μm, greater than 21 μm, less than 21 μm or equal to 21 μm, greater than 22 μm, less than 22 μm or equal to 22 μm, greater than 23 μm, less than 23 μm or equal to 23 μm,It may be greater than, less than, or equal to 24 μm, greater than, less than, or equal to 24 μm, greater than, less than, or equal to 25 μm, greater than, less than, or equal to 25 μm, greater than, less than, or equal to 26 μm, greater than, less than, or equal to 26 μm, greater than, less than, or equal to 27 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 29 μm, or greater than, less than, or equal to 30 μm. In some cases, the wall thickness of the individual coatings of the microencapsulated particles can range from about 500 nm to about 1 μm, 1 μm to about 10 μm, 1 μm to about 5 μm, 2 μm to about 7 μm, 3 μm to about 8 μm, 5 μm to about 10 μm, 5 μm to about 15 μm, or 1 μm to about 30 μm.

[0131] In some cases, the wall thickness of the microencapsulated particles can be increased by increasing the ratio of wall material to core material prior to spray drying. In some cases, the wall material to core material ratio (weight / weight) is about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79 1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1.

[0132] In some cases, the ratio of wall material to core material (weight / weight) can be about 10:1. In some cases, the wall thickness of the microencapsulated particles can be increased by increasing the ratio of wall material to already microencapsulated particles prior to spray drying. In some cases, the ratio of wall material to already microencapsulated particles (weight / weight) can be about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1 It can be 6:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1.

[0133] In some embodiments, among a plurality of microencapsulated particles, about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, 99% or 100% of the microencapsulated particles may comprise a core substantially encapsulated by wall material. In some cases, within a plurality of microencapsulated particles, about 1% to about 50%, 1% to about 20%, 1% to about 10%, 5% to about 25%, 10% to about 40%, 10% to about 60%, 20% to about 70%, 20% to about 50%, 30% to about 80%, 40% to about 90%, 50% to about 75%, 60% to about 80%, 70% to about 90%, 75% to about 95%, 80% to about 90%, 80% to about 99%, 85% to about 100%, or 90% to about 100% of the microencapsulated particles may comprise a core substantially encapsulated by wall material. In some cases, within a plurality of microencapsulated particles, not all of the core material may be encapsulated by wall material.

[0134] In certain cases, formulations may be prepared such that not all microencapsulated particles have the same number of coatings. This may be advantageous when delivery of an active ingredient may occur at multiple locations along the gastrointestinal tract. In some cases, among multiple microencapsulated particles, about 1% to about 50%, 1% to about 20%, 1% to about 10%, 5% to about 25%, 10% to about 40%, 10% to about 60%, 20% to about 70%, 20% to about 50%, 30% to about 80%, 40% to about 90%, 50% to about 75%, 60% to about 80%, 70% to about 90%, 75% to about 95%, 80% to about 90%, 80% to about 99%, 85% to about 100%, or 90% to about 100% of the microencapsulated particles may contain two or more coatings.

[0135] In some cases, varying the size or number of coatings can alter the drug release time. For example, small (e.g., about 20 μm to about 40 μm) encapsulated particles containing an additional enteric coating are readily absorbed from the intestine and into the bloodstream, whereas large enteric-coated encapsulated particles greater than about 60 μm may take longer to be absorbed into the bloodstream. In some cases, particles with a diameter of about 20 μm to about 40 μm may be absorbed more quickly than particles with a diameter of about 50 μm to about 200 μm. In some embodiments, particles with a size of about 50 μm to about 200 μm can be mixed with particles with a size of about 20 μm to about 40 μm. In some embodiments, the weight ratio of particles having a diameter of about 70 μm to about 100 μm to particles having a size of about 30 μm to about 60 μm is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 to about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:8, from about 1:1 to about 1:10, from about 1:2 to about 1:3, from about 1:2 to about 1:4, from about 1:2 to about 1:5 , about 1:2 to about 1:8, about 1:2 to about 1:10, about 1:3 to about 1:4, about 1:3 to about 1:5, about 1:3 to about 1:8, about 1:3 to about 1:10, about 1:4 to about 1:5, about 1:4 to about 1:8, about 1:4 to about 1:10, about 1:5 to about 1:8, about 1:5 to about 1:10, or 1:8 to about 1:10. In some embodiments, the weight ratio of particles having a diameter of about 70 μm to about 100 μm to particles having a size of about 30 μm to about 60 μm is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 to about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:8, from about 1:1 to about 1:10, from about 1:2 to about 1:3, from about 1:2 to about 1:4, from about 1:2 to about 1:5 , about 1:2 to about 1:8, about 1:2 to about 1:10, about 1:3 to about 1:4, about 1:3 to about 1:5, about 1:3 to about 1:8, about 1:3 to about 1:10, about 1:4 to about 1:5, about 1:4 to about 1:8, about 1:4 to about 1:10, about 1:5 to about 1:8, about 1:5 to about 1:10, or 1:8 to about 1:10.In some embodiments, larger sized particles (about 70 μm to about 200 μm) can be mixed with smaller sized particles (about 20 μm to about 40 μm). In some embodiments, the weight ratio of larger sized particles (about 70 μm to about 200 μm) to smaller sized particles (about 20 μm to about 40 μm) is about 1:1 to about 1:2, about 1:1 to about 1:3, about 1:1 to about 1:4, about 1:1 to about 1:5, about 1:1 to about 1:8, about 1:1 to about 1:10, about 1:2 to about 1:3, about 1:2 to about 1:4, about 1:2 ...5, about 1:2 to about 1:5, about 1:2 to about 1:5, about 1:2 to about 1:6, about 1:2 to about 1:7, about 1:2 to about 1:8, about 1:2 to about 1:9, about 1:3 to about 1:4, about 1:2 to about 1:5, about 1:1 to about 1:8, about 1:1 to about 1:10, about 1:2 to about 1:3, about 1:2 to about 1:4, about 1:2 to about 1:5, about 1:1 to about 1:5, about 1:1 to about 1:8, about 1:1 to about 1:10, about 1:2 to about 1:5, about from about 1:5, from about 1:2 to about 1:8, from about 1:2 to about 1:10, from about 1:3 to about 1:4, from about 1:3 to about 1:5, from about 1:3 to about 1:8, from about 1:3 to about 1:10, from about 1:4 to about 1:5, from about 1:4 to about 1:8, from about 1:4 to about 1:10, from about 1:5 to about 1:8, from about 1:5 to about 1:10, or 1:8 to about 1:10.

[0136] In some cases, the core diameter of the microencapsulated particles is greater than, less than, or equal to about 100 nm (nanometers), greater than, less than, or equal to 150 nm, greater than, less than, or equal to 200 nm, greater than, less than, or equal to 250 nm, greater than, less than, or equal to 300 nm, greater than, less than, or equal to 350 nm, greater than, less than, or equal to 400 nm, or equal to 400nm, greater than 450nm, less than 450nm or equal to 450nm, greater than 500nm, less than 500nm or equal to 500nm, greater than 550nm, less than 550nm or equal to 550nm, greater than 600nm, less than 600nm or equal to 600nm, greater than 650nm, less than 650nm or equal to 650nm, greater than 700nm, less than 700nm or equal to 700nm, greater than 750nm, less than 750nm or equal to 750nm, greater than 800nm, Less than or equal to 800nm, greater than 850nm, less than 850nm, or equal to 850nm, greater than 900nm, less than 900nm, or equal to 900nm, greater than 950nm, less than 950nm, or equal to 950nm, greater than 1µm, less than 1µm, or equal to 1µm, greater than 2µm, less than 2µm, or equal to 2µm, greater than 3µm, less than 3µm, or equal to 3µm, greater than 4µm, less than 4µm, or equal to 4µm, greater than 5µm, less than 5µm, or equal to 5µm, greater than 6 μm, less than 6 μm, or equal to 6 μm; greater than 7 μm, less than 7 μm, or equal to 7 μm; greater than 8 μm, less than 8 μm, or equal to 8 μm; greater than 9 μm, less than 9 μm, or equal to 9 μm; greater than 10 μm, less than 10 μm, or equal to 10 μm; greater than 11 μm, less than 11 μm, or equal to 11 μm; greater than 12 μm, less than 12 μm, or equal to 12 μm; greater than 13 μm, less than 13 μm, or equal to 13 μm; greater than 14 μm, less than 14 μm, or equal to 14 μm;More than 15 μm, less than 15 μm, or equal to 15 μm; more than 16 μm, less than 16 μm, or equal to 16 μm; more than 17 μm, less than 17 μm, or equal to 17 μm; more than 18 μm, less than 18 μm, or equal to 18 μm; more than 19 μm, less than 19 μm, or equal to 19 μm; more than 20 μm, less than 20 μm, or equal to 20 μm; more than 21 μm, less than 21 μm, or equal to 21 μm; more than 22 μm, less than 22 μm, or equal to 22 μm; 23 μm The diameter may be greater than, less than, or equal to 23 μm, greater than, less than, or equal to 24 μm, greater than, less than, or equal to 24 μm, greater than, less than, or equal to 25 μm, greater than, less than, or equal to 25 μm, greater than, less than, or equal to 26 μm, greater than, less than, or equal to 26 μm, greater than, less than, or equal to 27 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 29 μm, or greater than, less than, or equal to 30 μm. In some cases, the diameter of the core of the microencapsulated particles may range from about 100 nm to about 250 nm, 100 nm to about 500 nm, 100 nm to about 1 μm, 500 nm to about 1 μm, 1 μm to about 10 μm, 1 μm to about 5 μm, 2 μm to about 7 μm, 3 μm to about 8 μm, 5 μm to about 10 μm, 5 μm to about 15 μm, or 1 μm to about 30 μm. In some cases, the core may constitute about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, or 99% of the total microcapsule content (e.g., the total weight of the core and wall material). In some cases, the core may comprise about 1% to about 50%, 1% to about 20%, 1% to about 10%, 5% to about 25%, 10% to about 40%, 10% to about 60%, 20% to about 70%, 20% to about 50%, 30% to about 80%, 40% to about 90%, 50% to about 75%, or 1% to about 99% of the total microcapsule content. Method for producing a powdered pharmaceutical composition

[0137] In some cases, a method for producing a pharmaceutical composition may include creating particles by the methods described herein. In some cases, the particles may include an excipient (e.g., a pharmaceutically acceptable excipient), an active ingredient, or both. In some embodiments, a method for producing a powdered pharmaceutical composition may include mixing particles of a pharmaceutically acceptable excipient with particles containing an active ingredient or a pharmaceutically acceptable salt thereof in a mixer. In some cases, particles containing an active ingredient may be microencapsulated. For example, particles of a hormone receptor agonist may be microencapsulated with trehalose and / or, optionally, an HPMC or HPMCAS coating. In some cases, at least some of the particles of the pharmaceutically acceptable excipient may have a particle size ranging from about 50 micrometers to about 200 micrometers, as measured by a particle size analyzer using laser diffraction. In some cases, particles containing an active ingredient may have a particle size ranging from about 500 nanometers to about 15 micrometers, or from 1 micrometer to about 20 micrometers, as measured by a particle size analyzer using laser diffraction.

[0138] In some aspects, the method of creating a powdered pharmaceutical composition can include particles, at least a portion of which particles of the active ingredient or a pharmaceutically acceptable salt thereof can be created by a spray drying process.

[0139] In some aspects, the spray drying process may involve atomizing droplets comprising the active ingredient or a pharmaceutically acceptable salt thereof, drying the droplets from particles, recovering the particles, or any combination thereof.

[0140] In some embodiments, the spray-drying manufacturing system may include a closed spray-drying vessel that receives a solution containing a drug dissolved or mixed in a suitable solvent (aqueous or solvent-based). In some cases, the solvent may include alcohol, ethanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), a polar organic solvent, an organic solvent, or any combination thereof. In some embodiments, the solution then enters a particle-forming chamber, which may be connected to an atomizer located at the top of the chamber. In some embodiments, the atomizer may be a two-component or rotary nozzle type that disperses the solution into fine droplets controlled by atomizer pressure. In some embodiments, the atomizing gas may be an inert gas. As used herein, "inert gas" may refer to a non-reactive gas or a gas that does not undergo chemical reactions under a set of given conditions. Inert gases can generally be used to avoid unwanted chemical reactions that degrade samples or to prevent bacterial growth. These undesirable chemical reactions are often oxidation and hydrolysis reactions with oxygen and moisture in the air. The term "inert gas" can be context-dependent, as some noble gases historically referred to as inert gases may become reactive under certain conditions. In some embodiments, the inert gas can be air, nitrogen, carbon dioxide, or any combination thereof. In some embodiments, the atomized droplets are passed through a hot gas drying chamber to produce uniform fine particles that maintain a small, coherent particle size distribution after evaporation of the liquid. In some cases, solid particles are formed and fall to the bottom of the drying chamber. In some cases, the drying process can be controlled by a balance between temperature, flow rate, and droplet size. In some embodiments, the powder can be collected from the exhaust gas using a cyclone or bag filter. In some embodiments, the particle size can be verified by a Malvern particle analyzer before blending with the excipient carrier. In some embodiments, the active powder (e.g., powdered pharmaceutical composition) can be blended with the excipient carrier (lactose) product in a Patterson Kelly (PK Blender), and the blended powder can be fed into a hopper.In some embodiments, from the hopper, the dry powder can be placed into size 3 hypromellose capsules by a Bosch Encapsulator machine. In some cases, the dry powder can be placed into any capsule of any size. For example, the dry powder can be placed into a size 000, 00, 0, 1, 2, 3, or 4 capsule.

[0141] The moisture level of the powder after spray drying can be less than about 10%. In some embodiments, the moisture level can be less than about 15%, less than about 14%, less than about 13%, less than about 12%, less than about 11%, less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1%.

[0142] In some embodiments, the method of making a composition may include formulating the particles described herein into a capsule-in-capsule composition (e.g., a pharmaceutical composition). In some cases, the particles may include an excipient, an active ingredient, or both. In some cases, the particles may include a carrier, an active ingredient, or both. In some cases, the particles may include a diluent, an active ingredient, or both. In some embodiments, the capsule-in-capsule formulation may be in the form of a unit dose. In some cases, the particles may be at least partially encapsulated by a coating material. In some cases, the particles at least partially encapsulated by a coating material may be spray-dried. In some cases, the particles may be at least partially surrounded by a first capsule, a second capsule, or both. In some cases, the first capsule may be surrounded by a second capsule to create a capsule that is a capsule-in-capsule. In some cases, the capsule may include a capsule coating. In some cases, the capsule coating may at least partially control the release of the capsule ingredients.

[0143] In some embodiments, the final product may be a capsule-in-capsule. In some cases, the final product may be a capsule (e.g., a second capsule) that surrounds an active ingredient (e.g., a hormone receptor agonist), and an inner capsule (e.g., a first capsule) that may contain its own active ingredient separately. In some cases, a capsule may contain more than one active ingredient. In some cases, a capsule may contain more than one inner capsule. For example, a capsule may contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more inner capsules. In some cases, an inner capsule may contain a capsule. For example, an outer capsule may surround a first inner capsule, and the first inner capsule may surround a second inner capsule. In some cases, the active ingredient may include a steroid, a human growth hormone receptor agonist, or a glucagon-like peptide 1 receptor agonist. In some cases, the active ingredient may be microencapsulated and spray-dried. In some cases, the active ingredient may be spray dried but not microencapsulated.

[0144] The process described herein may include the following manufacturing steps: The active ingredients of the first capsule and the second capsule can be microencapsulated and spray-dried using the methods described herein. In some embodiments, the active ingredients can be independently blended with excipients. In some cases, the active ingredients do not need to be blended with excipients. In some cases, the active ingredients of the first capsule can then be added to the first capsule, and the first capsule can be banded using the methods described herein. In some cases, after banding the first capsule, a capsule coating (e.g., enteric, pH-dependent, time-release, or combination release) can be applied to the first capsule. In some cases, the active ingredients of the second capsule can then be added to the second capsule, and the first capsule can be placed into the second capsule. The second capsule can then be banded, and a capsule coating can be applied to the second capsule.

[0145] In some embodiments, the capsule may further comprise a capsule coating. In some cases, a capsule coating may be added to the capsule to further improve stability (protection from light, moisture and gas barrier), facilitate administration, or modify the release behavior of the composition from the dosage form. A capsule coating may be used to enable immediate release of the composition, delayed release of the composition (e.g., as with an enteric coating), or sustained release of the composition. In some cases, the capsule coating may comprise a film coating, a gelatin coating, or both. In some cases, the capsule coating may comprise an enteric coating, a time-release coating, a pH-dependent coating, a delayed-release coating, an extended-release coating, or a combination thereof. For example, an enteric coating may be added to the capsule to prevent dissolution until it has passed through the stomach. In some cases, the composition may be released according to the pH value in the gastrointestinal (GI) tract. The GI tract may have different pH values, allowing for pH-dependent dosing in specific areas. For example, the pH of the stomach (an acidic pH of approximately 1.5 to 4.0) differs from the pH of the small intestine (pH 4.0 to 7.0), and pH coatings can be used to deliver medication to regions of the GI tract with specific pH levels. In some embodiments, the enteric coating of the capsule can be a polymer barrier that can be applied to the capsules described herein to enable controlled release. Bypassing the stomach can enable more precise dosing and can also enable greater bioavailability of the drug in the gastrointestinal tract. In some cases, these coatings can modify the delivery of drugs from the mouth all the way to the colon. In some cases, this technology can be applied to an outer capsule (e.g., a second capsule) and an inner capsule (e.g., a first capsule) in a capsule-in-capsule technique, and the intended drug delivery can be achieved using timed release, pH-controlled release, or a combination of both technologies.In some cases, enteric coatings can be applied to multiple capsules, for example, to the inner and outer capsules, to provide delayed release of both capsules. In some cases, capsule coatings can provide color, mask bitterness, or both. In some cases, capsule coatings can include polymers, plasticizers, pigments, opacifiers, lubricants, binders, anti-tacking agents, anti-foaming mechanisms, surfactants, fillers, and extenders.

[0146] In certain cases, the pharmaceutical formulation does not contain a surfactant. In other cases, the pharmaceutical formulation contains a surfactant. The surfactant can be a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, and a triglyceride. Examples of nonionic surfactants include, but are not limited to, cocamide monoethanolamine (Cocamide MEA), cocamide diethanolamine (Cocamide DEA), fatty alcohol ethoxylates, Tween® 20, Tween® 40, Tween® 60, and Tween® 80. Examples of anionic surfactants include, but are not limited to, sodium lauryl sulfate (SLS), sodium laureth sulfate (SLES), ammonium lauryl sulfate (ALS), ammonium laureth sulfate (ALES), sodium stearate, and potassium cocoate. Examples of cationic surfactants include, but are not limited to, tetramethylammonium chloride, tetrapropylammonium hydroxide, tetrabutylammonium bromide, tetrabutylammonium hydroxide, trimethylphenylammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, and benzyltributylammonium chloride. Examples of amphoteric surfactants include, but are not limited to, alkylamidopropylamine N-oxide (APAO), alkyldimethylamine N-oxide (AO), alkylbetaine (Bt), and alkylamidopropylbetaine (APB).

[0147] In some embodiments, the enteric coating may include a polymer, such as methyl acrylate-methacrylic acid copolymer, cellulose acetate phthalate, methyl methacrylate (MMA), cellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate (hypromellose acetate succinate), polyvinyl acetate phthalate, methyl methacrylate-methacrylic acid copolymer, shellac, cellulose acetate trimellitate, sodium alginate, zein, ethyl cellulose, medium chain triglycerides, oleic acid, stearic acid, or any combination thereof.

[0148] In some embodiments, the capsule can be configured (e.g., with a capsule coating) to at least partially release the active ingredient in the mouth, esophagus, small intestine, duodenum, jejunum, ileum, cecum, colon, ascending colon, transverse colon, descending colon, sigmoid colon, rectum, anus, or any combination thereof.

[0149] In some cases, the composition may comprise a mixture of particles described herein. In some cases, at least a portion of the excipients and at least a portion of the particles comprising the active ingredient may comprise a mixture or formulation. Microencapsulation

[0150] In some embodiments, encapsulation can include microencapsulation. Microencapsulation can be a process that can create microcapsules as small spheres or multiple spheres with a core surrounded by a matrix wall. The pharmaceutical ingredient inside the microcapsule can be referred to as the content. In some cases, the content can be a liquid, oil, solid, or any combination thereof. The wall around the content (or "core") can be referred to as a shell, coating, or membrane. Microcapsules can have diameters as small as 1.0 micron to about 10.0 microns, or from about 1.0 micron to about 5.0 microns. In some cases, small size can provide the pharmaceutical ingredient with a large surface area available for absorption, release, migration, or any combination thereof. In some cases, microencapsulation can at least partially prevent inhalation of active ingredients, including unencapsulated crystalline forms. For example, microencapsulation can at least partially prevent inhalation of unencapsulated crystals, including hormone receptor agonists. In some cases, unencapsulated crystals, such as hormone receptor agonist crystals, may cause irritation of the subject's airway during inhalation.Irritation can be caused by the geometry and structure of the crystal.For example, crystals may have sharp corners and edges that can cause irritation, damage, or both to the airway during inhalation.In some cases, the geometry and structure of crystals can be controlled by the spray-drying process.By microencapsulation, crystals with amorphous structure can be produced.In some cases, amorphous crystals may lack sharp edges and corners.In some cases, amorphous crystals may have rounded edges.In some cases, amorphous crystals may have increased bioavailability.

[0151] In some cases, the agonist described herein contained in oil can be microencapsulated with a compatible diluent to protect the oil from oxidation and provide a longer shelf life than unprotected pharmaceutical compositions.Similarly, hormone receptor agonist can be encapsulated to provide a longer shelf life.Diluent can be aqueous or solvent-based, and use animal or plant materials. In some cases, the diluent may include alcohols such as ethanol, butanol, 2-ethylhexanol, isobutanol, isopropanol, methanol, propanol, and propylene glycol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl isopropyl ketone, mesityl oxide, and trichloroethylene; halogenated solvents such as ethylene bromide, chloroform, ethylene chloride, dichloromethane, tetrachloroethylene, and carbon tetrachloride; amides such as dimethylformamide; ethers such as 1,4-dioxane, butyl ether, ethyl ether, diisopropyl ether, tetrahydrofuran, and tert-butyl methyl ether; sulfur-containing solvents such as dimethyl sulfoxide; amines such as pyridine; nitriles such as acetonitrile; esters such as ethyl acetate; aliphatic hydrocarbons such as cyclohexane and hexane; aromatic hydrocarbons such as toluene and xylene; water, or any combination thereof. In some cases, the diluent may include benzene, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, 1,1,1-trichloroethane, acetonitrile, chlorobenzene, chloroform, cyclohexane, 1,2-dichloroethane, dichloromethane, 1,2-dimethoxyethane, N,N-dimethylacetamide, N,N-dimethylformamide, 1,4-dioxane, 2-ethoxyethanol, ethylene glycol, formamide, hexane, methanol, 2-methoxyethanol, methyl butyl ketone, methylcyclohexane, n-methylpyrrolidone, nitromethane, pyridine, sulfolane, tetralin, toluene, 1,1,2-trichloroethylene, xylene, or any combination thereof.

[0152] The active ingredient core can be microencapsulated using amphiphilic molecules that have both a polar end ("hydrophilic") and a non-polar end ("hydrophobic"). In some cases, the hydrophilic end of the amphiphilic molecule can interact with the core material. In some cases, the hydrophobic end of the amphiphilic molecule can interact with the core material. This hydrophilic and hydrophobic structure can allow the molecule to microencapsulate the active ingredient and form a microsphere. In some cases, the microencapsulated particles can have a hydrophilic exterior and a hydrophobic interior. In some cases, the microencapsulated particles can have a hydrophobic exterior and a hydrophilic interior. The microencapsulation process can coat the active ingredient core with the amphiphilic encapsulant wall material, thereby at least partially surrounding the active ingredient within the amphiphilic wall. For example, hydroxypropyl methylcellulose acetate succinate (HPMCAS) can be an amphiphilic molecule used to coat hormone receptor agonists. The microencapsulated blend may be a spray-dried dispersion and fed into a spray-drying system to create a hard outer coating on the microcapsules.

[0153] The wall material can form an adhesive film to the active ingredient core. A wide variety of coating materials are available for encapsulation, including traditional coating materials such as inert polymers and pH-sensitive polymers, such as carboxylic acid and amino derivatives, which swell or dissolve depending on the degree of crosslinking. Additionally, several innovative coating polymers have been developed, particularly for bioadhesive and mucoadhesive applications. In some cases, the coating material can be a hydrophilic polymer, a hydrophobic polymer, or a combination of both. In some cases, the microcapsule shell can contain amphiphilic molecules. In some cases, the coating material can be gelatin, polyvinyl alcohol, ethyl cellulose, cellulose acetate phthalate, or styrene maleic anhydride. In some cases, the coating material can be non-reactive with the pharmaceutical ingredient. In some cases, the microcapsule shell can contain trehalose, hydroxypropyl methylcellulose ("HPMC"), hydroxypropyl methylcellulose acetate succinate ("HPMCAS"), cyclodextrin, maltodextrin, povidone, copovidone, and others. In some cases, the microcapsule shell may contain HPMCAS-LG, HPMCAS-MG, HPMCAS-HG, or HPMC-P, or a combination thereof. In some cases, the microcapsule shell may contain different grades of HPMC or HPMCAS. For example, the microcapsule shell may contain E5, E50, or K4M grade HPMC. In another example, the microcapsule shell may contain L, M, or H grade HPMCAS. In some cases, the microcapsule shell may contain trehalose and / or HPMCAS. In some cases, the microcapsule shell may contain gelatin, corn starch, polyvinylpyrrolidone (PVP), oligosaccharides, starch, cellulose, glycogen, long-chain sugars, or any combination thereof. In some cases, the microcapsule shell may contain FDKP (fumaryl diketopiperazine). In some cases, the microcapsule shell may contain 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).

[0154] In some cases, the microcapsule shell comprises a ratio of DSPC to FDKP of about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79:1, 80:1, 81:1, 82:1, 83: 1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, or 100:1 weight ratio (DSPC to FDKP). In some cases, the microcapsule shell comprises a mixture of FDKP and DSPC in a ratio of about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79:1, 80:1, 81:1, 82:1, 1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, or 100:1 weight ratio (FDKP to DSPC).

[0155] In some cases, the microcapsule shell may comprise fatty acids, liposomes, amino acids, natural oils and sugars, trehalose, dextran, natural oils, synthetic oils, or combinations thereof. In some cases, the sugar may comprise dextrose, fructose, galactose, glucose, lactose, maltose, sucrose, a salt of any of these, or any combination thereof. In some cases, the amino acid may comprise glutamic acid, aspartic acid, lysine, tryptophan, tyrosine, methionine, or a combination thereof. In some cases, the fatty acid may comprise polyunsaturated fatty acids, essential fatty acids, conjugated fatty acids, short-chain fatty acids, medium-chain fatty acids, long-chain fatty acids, very long-chain fatty acids, saturated fatty acids, unsaturated fatty acids, monounsaturated fats, or any combination thereof. In some cases, the fatty acid may comprise omega-3 fatty acids, omega-5 fatty acids, omega-6 fatty acids, omega-7 fatty acids, omega-9 fatty acids, omega-10 fatty acids, omega-11 fatty acids, omega-12 fatty acids, or a combination thereof. In some cases, the natural oil can include soybean oil, vegetable oil, edible oil, evening primrose oil, borage oil, black currant seed oil, flax or linseed oil, rapeseed or canola oil, corn oil, almond oil, avocado oil, Brazil nut oil, canola oil, cashew oil, chia seed oil, cocoa butter oil, coconut oil, corn oil, cottonseed oil, flaxseed / linseed oil, grapeseed oil, hemp seed oil, black gram oil, mustard oil, olive oil, palm oil, peanut oil, pecan oil, perilla oil, rice bran oil, safflower oil, sesame oil, soybean oil, walnut oil, sunflower oil, cottonseed oil, palm oil, or combinations thereof.In some cases, the microcapsule shell can increase or decrease the release kinetics of the active ingredient. In some cases, the microcapsule shell can increase or decrease bioavailability.In some cases, microencapsulation of a hormone receptor agonist can result in a bioavailability of the hormone receptor agonist that is about 5% to about 70%, 5% to about 10%, 5% to about 20%, 10% to about 30%, 15% to about 40%, 25% to about 40%, 10% to about 60%, or about 20% to about 50% higher when inhaled into a subject compared to the unencapsulated hormone receptor agonist. The wall material can be biodegradable and biocompatible with the pharmaceutical ingredient. In some cases, microcapsules can be made by dissolving or mixing the pharmaceutical ingredient in a solvent containing the shell material to form a liquid suspension. For example, HPMCAS can be dissolved in ethanol and water, and the pharmaceutical compound can be added to the liquid suspension. In some cases, the pharmaceutical compound may not dissolve in the liquid suspension. In some cases, the pharmaceutical compound may dissolve in the liquid suspension. The liquid suspension can be dried using the spray drying techniques described herein or by another method.

[0156] In some cases, the average wall thickness of the microencapsulated particles is greater than, less than, or equal to about 500 nm, greater than, less than, or equal to 550 nm, greater than, less than, or equal to 550 nm, greater than, less than, or equal to 600 nm, greater than, less than, or equal to 650 nm, greater than, less than, or equal to 700 nm, greater than, less than, or equal to 700 nm, greater than, less than, or equal to 750 nm, greater than, less than, or equal to 750 nm, greater than, less than, or equal to 800 nm, or greater than, less than, or equal to 800 nm. 00nm or equal to 00nm, greater than 850nm, less than 850nm or equal to 850nm, greater than 900nm, less than 900nm or equal to 900nm, greater than 950nm, less than 950nm or equal to 950nm, greater than 1μm, less than 1μm or equal to 1μm, greater than 2μm, less than 2μm or equal to 2μm, greater than 3μm, less than 3μm or equal to 3μm, greater than 4μm, less than 4μm or equal to 4μm, greater than 5μm, less than 5μm or equal to 5μm, greater than 6μm, less than 6μm , or equal to 6 μm, greater than 7 μm, less than 7 μm, or equal to 7 μm, greater than 8 μm, less than 8 μm, or equal to 8 μm, greater than 9 μm, less than 9 μm, or equal to 9 μm, greater than 10 μm, less than 10 μm, or equal to 10 μm, greater than 11 μm, less than 11 μm, or equal to 11 μm, greater than 12 μm, less than 12 μm, or equal to 12 μm, greater than 13 μm, less than 13 μm, or equal to 13 μm, greater than 14 μm, less than 14 μm, or equal to 14 μm, greater than 15 μm, 15 μm less than or equal to 15 μm, greater than 16 μm, less than 16 μm, or equal to 16 μm, greater than 17 μm, less than 17 μm, or equal to 17 μm, greater than 18 μm, less than 18 μm, or equal to 18 μm, greater than 19 μm, less than 19 μm, or equal to 19 μm, greater than 20 μm, less than 20 μm, or equal to 20 μm, greater than 21 μm, less than 21 μm, or equal to 21 μm, greater than 22 μm, less than 22 μm, or equal to 22 μm, greater than 23 μm, less than 23 μm, or equal to 23 μm,The thickness may be greater than, less than, or equal to 24 μm, greater than, less than, or equal to 25 μm, greater than, less than, or equal to 26 μm, greater than, less than, or equal to 27 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 29 μm, or greater than, less than, or equal to 30 μm. In some cases, the wall thickness of the microencapsulated particles may range from about 1 μm to about 10 μm, 1 μm to about 5 μm, 2 μm to about 7 μm, 3 μm to about 8 μm, 5 μm to about 10 μm, 5 μm to about 15 μm, or 1 μm to about 30 μm. In some cases, the wall thickness of the microencapsulated particles can be increased by increasing the ratio of wall material to core material before spray drying. In some cases, the wall material to core material ratio (weight / weight) is about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79: The wall thickness may be 1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1. In some cases, the ratio (weight / weight) of the wall material to the core material may be about 10:1. In some cases, the pharmaceutical composition herein may include particles of the pharmaceutical composition having different wall thicknesses. For example, the metformin particles herein may be microencapsulated, and the microencapsulated particles have one, two, three, four, or more different wall thicknesses. In some cases, different wall thicknesses can alter the drug release of particles. For example, thicker walled microencapsulated particles have delayed drug release compared to thinner walled microencapsulated particles.

[0157] In some embodiments, among a plurality of microencapsulated particles, about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, 99%, or 100% of the microencapsulated particles may comprise a core substantially encapsulated by wall material. In some cases, within a plurality of microencapsulated particles, about 1% to about 50%, 1% to about 20%, 1% to about 10%, 5% to about 25%, 10% to about 40%, 10% to about 60%, 20% to about 70%, 20% to about 50%, 30% to about 80%, 40% to about 90%, 50% to about 75%, 60% to about 80%, 70% to about 90%, 75% to about 95%, 80% to about 90%, 80% to about 99%, 85% to about 100%, or 90% to about 100% of the microencapsulated particles may comprise a core substantially encapsulated by wall material. In some cases, within a plurality of microencapsulated particles, not all of the core material may be encapsulated by wall material.

[0158] In some embodiments, the mean, median, or mode particle size of the microencapsulated particles is less than about 500 nm, less than 1 μm, less than 2 μm, less than 3 μm, less than 4 μm, less than 5 μm, less than 6 μm, less than 7 μm, less than 8 μm, less than 9 μm, less than 10 μm, less than 11 μm, less than 12 μm, less than 13 μm, less than 14 μm, or less than 15 μm. In some embodiments, the mean, median, or mode particle size of the microencapsulated particles is greater than or equal to about 500 nm, greater than or equal to 1 μm, greater than or equal to 2 μm, greater than or equal to 3 μm, greater than or equal to 4 μm, greater than or equal to 5 μm, greater than or equal to 6 μm, greater than or equal to 7 μm, greater than or equal to 8 μm, greater than or equal to 9 μm, greater than or equal to 10 μm, greater than or equal to 11 μm, greater than or equal to 12 μm, greater than or equal to 13 μm, greater than or equal to 14 μm, or greater than or equal to 15 μm. In some embodiments, the mean, median, or mode particle size of the microencapsulated particles ranges from about 500 nm to about 5 μm, 1 μm to about 10 μm, 1 μm to about 5 μm, 2 μm to about 7 μm, 3 μm to about 8 μm, 5 μm to about 10 μm, or 5 μm to about 15 μm.

[0159] In some embodiments, the mean, median, or mode particle size of the microencapsulated particles is less than about 500 nm, less than 1 μm, less than 2 μm, less than 3 μm, less than 4 μm, less than 5 μm, less than 6 μm, less than 7 μm, less than 8 μm, less than 9 μm, less than 10 μm, less than 11 μm, less than 12 μm, less than 13 μm, less than 14 μm, less than 15 μm, less than 16 μm, less than 17 μm, less than 18 μm, less than 19 μm, less than 20 μm, less than 21 μm, less than 22 μm, less than 23 μm, less than 24 μm, less than 25 μm, less than 26 μm, less than 27 μm, less than 28 μm, less than 29 μm, less than 30 μm Less than 31 μm, Less than 32 μm, Less than 33 μm, Less than 34 μm, Less than 35 μm, Less than 36 μm, Less than 37 μm, Less than 38 μm, Less than 39 μm, Less than 40 μm, Less than 41 μm, Less than 42 μm, Less than 43 μm, Less than 44 μm, Less than 45 μm, Less than 46 μm, Less than 47 μm, Less than 48 μm, Less than 49 μm, Less than 50 μm, Less than 51 μm, Less than 52 μm, Less than 53 μm, Less than 54 μm, Less than 55 μm, Less than 56 μm, Less than 57 μm, Less than 58 μm, Less than 59 μm, Less than 60 μm, Less than 61 μm, Less than 62 μm, Less than 63 μm, Less than 64 μm, Less than 65 μm, 6 Less than 6 μm, Less than 67 μm, Less than 68 μm, Less than 69 μm, Less than 70 μm, Less than 71 μm, Less than 72 μm, Less than 73 μm, Less than 74 μm, Less than 75 μm, Less than 76 μm, Less than 77 μm, Less than 78 μm, Less than 79 μm, Less than 80 μm, Less than 81 μm, Less than 82 μm, Less than 83 μm, Less than 84 μm, Less than 85 μm, Less than 86 μm, Less than 87 μm, Less than 88 μm, Less than 89 μm, Less than 90 μm, Less than 91 μm, Less than 92 μm, Less than 93 μm, Less than 94 μm, Less than 95 μm, Less than 96 μm, Less than 97 μm, Less than 98 μm, Less than 99 μm, Less than 100 μm, 101 μm less than, less than 102 μm, less than 103 μm, less than 104 μm, less than 105 μm, less than 106 μm, less than 107 μm, less than 108 μm, less than 109 μm, less than 110 μm, less than 111 μm, less than 112 μm, less than 113 μm, less than 114 μm, less than 115 μm, less than 116 μm, less than 117 μm, less than 118 μm, less than 119 μm, less than 120 μm, less than 121 μm, less than 122 μm, less than 123 μm, less than 124 μm, less than 125 μm, less than 126 μm, less than 127 μm, less than 128 μm, less than 129 μm, less than 130 μm, less than 131 μm, less than 132 μm,Less than 133 μm, Less than 134 μm, Less than 135 μm, Less than 136 μm, Less than 137 μm, Less than 138 μm, Less than 139 μm, Less than 140 μm, Less than 141 μm, Less than 142 μm, Less than 143 μm, Less than 144 μm, Less than 145 μm, Less than 146 μm, Less than 147 μm, Less than 148 μm, Less than 149 μm, Less than 150 μm, Less than 151 μm, Less than 152 μm, Less than 153 μm, Less than 154 μm, Less than 155 μm, Less than 156 μm, Less than 157 μm, Less than 158 μm, Less than 159 μm, Less than 160 μm, Less than 161 μm, Less than 162 μm, Less than 163 μm, Less than 164 μm, Less than 165 μm, Less than 166 μm, Less than 167 μm

[0033] The thickness may be less than 168 μm, less than 169 μm, less than 170 μm, less than 171 μm, less than 172 μm, less than 173 μm, less than 174 μm, less than 175 μm, less than 176 μm, less than 177 μm, less than 178 μm, less than 179 μm, less than 180 μm, less than 181 μm, less than 182 μm, less than 183 μm, less than 184 μm, less than 185 μm, less than 186 μm, less than 187 μm, less than 188 μm, less than 189 μm, less than 190 μm, less than 191 μm, less than 192 μm, less than 193 μm, less than 194 μm, less than 195 μm, less than 196 μm, less than 197 μm, less than 198 μm, less than 199 μm, or less than 200 μm. In some embodiments, the mean, median, or mode particle size of the microencapsulated particles is greater than or equal to about 500 nm, greater than or equal to 1 μm, greater than or equal to 2 μm, greater than or equal to 3 μm, greater than or equal to 4 μm, greater than or equal to 5 μm, greater than or equal to 6 μm, greater than or equal to 7 μm, greater than or equal to 8 μm, 9 μm, or less. greater than or equal to 9 μm, greater than or equal to 10 μm, greater than or equal to 11 μm, greater than or equal to 12 μm, greater than or equal to 13 μm, greater than or equal to 14 μm, greater than or equal to 15 μm, greater than or equal to 16 μm, greater than or equal to 17 μm, greater than or equal to 18 μm, greater than or equal to 18 μm, greater than or equal to 19 μm,Greater than or equal to 20 μm, greater than or equal to 21 μm, greater than or equal to 22 μm, greater than or equal to 23 μm, greater than or equal to 24 μm, greater than or equal to 25 μm, greater than or equal to 26 μm, greater than or equal to 27 μm, greater than or equal to 28 μm, greater than or equal to 29 μm, greater than or equal to 30 μm, greater than or equal to 31 μm m, greater than or equal to 32 μm, greater than or equal to 32 μm, greater than or equal to 33 μm, greater than or equal to 34 μm, greater than or equal to 34 μm, greater than or equal to 35 μm, greater than or equal to 36 μm, greater than or equal to 36 μm, greater than or equal to 37 μm, greater than or equal to 38 μm, greater than or equal to 38 μm, greater than or equal to 39 μm, greater than or equal to 40 μm, greater than or equal to 41 μm, greater than or equal to 41 μm, greater than or equal to 42 μm, greater than or equal to 42 μm, greater than or equal to 43 μm greater than or equal to 43 μm, greater than or equal to 44 μm, greater than or equal to 45 μm, greater than or equal to 46 μm, greater than or equal to 47 μm, greater than or equal to 48 μm, greater than or equal to 48 μm, greater than or equal to 49 μm, greater than or equal to 50 μm, greater than or equal to 51 μm, greater than or equal to 51 μm, greater than or equal to 52 μm, greater than or equal to 53 μm, greater than or equal to 54 μm, 55 μm greater than or equal to 55 μm, greater than or equal to 56 μm, greater than or equal to 56 μm, greater than or equal to 57 μm, greater than or equal to 58 μm, greater than or equal to 58 μm, greater than or equal to 59 μm, greater than or equal to 60 μm, greater than or equal to 61 μm, greater than or equal to 62 μm, greater than or equal to 63 μm, greater than or equal to 64 μm, greater than or equal to 65 μm, greater than or equal to 66 μm,Greater than or equal to 67 μm, greater than or equal to 68 μm, greater than or equal to 68 μm, greater than or equal to 69 μm, greater than or equal to 70 μm, greater than or equal to 71 μm, greater than or equal to 72 μm, greater than or equal to 73 μm, greater than or equal to 74 μm, greater than or equal to 75 μm, greater than or equal to 76 μm, greater than or equal to 77 μm, greater than or equal to 77 μm, greater than or equal to 78 μm greater than or equal to 79 μm, greater than or equal to 80 μm, greater than or equal to 80 μm, greater than or equal to 81 μm, greater than or equal to 82 μm, greater than or equal to 82 μm, greater than or equal to 83 μm, greater than or equal to 83 μm, greater than or equal to 84 μm, greater than or equal to 85 μm, greater than or equal to 86 μm, greater than or equal to 86 μm, greater than or equal to 87 μm, greater than or equal to 88 μm, greater than or equal to 88 μm, greater than or equal to 89 μm, greater than or equal to 90 μm 0 μm, greater than or equal to 91 μm, greater than or equal to 92 μm, greater than or equal to 92 μm, greater than or equal to 93 μm, greater than or equal to 94 μm, greater than or equal to 95 μm, greater than or equal to 96 μm, greater than or equal to 96 μm, greater than or equal to 97 μm, greater than or equal to 98 μm, greater than or equal to 98 μm, greater than or equal to 99 μm, greater than or equal to 100 μm, greater than or equal to 101 μm, 102 μm greater than or equal to 102 μm, greater than or equal to 103 μm, greater than or equal to 103 μm, greater than or equal to 104 μm, greater than or equal to 104 μm, greater than or equal to 105 μm, greater than or equal to 106 μm, greater than or equal to 106 μm, greater than or equal to 107 μm, greater than or equal to 107 μm, greater than or equal to 108 μm, greater than or equal to 108 μm, greater than or equal to 109 μm, greater than or equal to 110 μm, greater than or equal to 110 μm, greater than or equal to 111 μm, greater than or equal to 112 μm,Greater than or equal to 113 μm, greater than or equal to 114 μm, greater than or equal to 114 μm, greater than or equal to 115 μm, greater than or equal to 115 μm, greater than or equal to 116 μm, greater than or equal to 117 μm, greater than or equal to 118 μm, greater than or equal to 118 μm, greater than or equal to 119 μm, greater than or equal to 120 μm, greater than or equal to 121 μm, greater than or equal to 122 μm, greater than or equal to 122 μm, greater than or equal to 123 μm m, greater than or equal to 124 μm, greater than or equal to 124 μm, greater than or equal to 125 μm, greater than or equal to 125 μm, greater than or equal to 126 μm, greater than or equal to 127 μm, greater than or equal to 127 μm, greater than or equal to 128 μm, greater than or equal to 128 μm, greater than or equal to 129 μm, greater than or equal to 130 μm, greater than or equal to 131 μm, greater than or equal to 131 μm, greater than or equal to 132 μm, greater than or equal to 133 μm, greater than or equal to 134 μm or equal to 134 μm, greater than 135 μm or equal to 135 μm, greater than 136 μm or equal to 136 μm, greater than 137 μm or equal to 137 μm, greater than 138 μm or equal to 138 μm, greater than 139 μm or equal to 139 μm, greater than 140 μm or equal to 140 μm, greater than 141 μm or equal to 141 μm, greater than 142 μm or equal to 142 μm, greater than 143 μm or equal to 143 μm, greater than 144 μm or equal to 144 μm, 145 μm greater than or equal to 145 μm, greater than or equal to 146 μm, greater than or equal to 146 μm, greater than or equal to 147 μm, greater than or equal to 147 μm, greater than or equal to 148 μm, greater than or equal to 148 μm, greater than or equal to 149 μm, greater than or equal to 150 μm, greater than or equal to 151 μm, greater than or equal to 151 μm, greater than or equal to 152 μm, greater than or equal to 153 μm, greater than or equal to 153 μm, greater than or equal to 154 μm, greater than or equal to 155 μm,greater than or equal to 156 μm, greater than or equal to 157 μm, greater than or equal to 157 μm, greater than or equal to 158 μm, greater than or equal to 158 μm, greater than or equal to 159 μm, greater than or equal to 160 μm, greater than or equal to 161 μm, greater than or equal to 161 μm, greater than or equal to 162 μm, Equal to 62 μm, greater than or equal to 163 μm, greater than or equal to 164 μm, greater than or equal to 164 μm, greater than or equal to 165 μm, greater than or equal to 165 μm, greater than or equal to 166 μm, greater than or equal to 167 μm, greater than or equal to 168 μm, greater than or equal to 168 μm, greater than or equal to 169 μm, greater than or equal to 170 μm, greater than or equal to 171 μm, 172 μm greater than or equal to 172 μm, greater than or equal to 173 μm, greater than or equal to 173 μm, greater than or equal to 174 μm, greater than or equal to 174 μm, greater than or equal to 175 μm, greater than or equal to 176 μm, greater than or equal to 176 μm, greater than or equal to 177 μm, greater than or equal to 178 μm, greater than or equal to 178 μm, greater than or equal to 179 μm, greater than or equal to 180 μm, greater than or equal to 181 μm greater than or equal to 182 μm, greater than or equal to 182 μm, greater than or equal to 183 μm, greater than or equal to 183 μm, greater than or equal to 184 μm, greater than or equal to 184 μm, greater than or equal to 185 μm, greater than or equal to 186 μm, greater than or equal to 186 μm, greater than or equal to 187 μm, greater than or equal to 188 μm, greater than or equal to 188 μm, greater than or equal to 189 μm, greater than or equal to 190 μm, greater than or equal to 191 μm or equal to 191 μm, greater than or equal to 192 μm, greater than or equal to 192 μm, greater than or equal to 193 μm, greater than or equal to 194 μm, greater than or equal to 195 μm, greater than or equal to 196 μm, greater than or equal to 196 μm, greater than or equal to 197 μm, greater than or equal to 198 μm, greater than or equal to 198 μm, greater than or equal to 199 μm, or greater than or equal to 200 μm.In some embodiments, the mean, median, or mode particle size of the microencapsulated particles ranges from about 500 nm to about 5 μm, 1 μm to about 10 μm, 1 μm to about 5 μm, 2 μm to about 7 μm, 3 μm to about 8 μm, 5 μm to about 10 μm, 5 μm to about 15 μm, 10 μm to about 50 μm, 20 μm to about 100 μm, 30 μm to about 70 μm, 50 μm to about 150 μm, 70 μm to about 100 μm, 70 μm to about 140 μm, 100 μm to about 180 μm, or 120 μm to about 200 μm. In some cases, the microencapsulated particles in a capsule-in-capsule formulation may be larger than the microencapsulated particles used in a dry powder inhalable formulation.

[0160] The core material may be a material onto which a coating is applied to achieve a specific purpose. The core material may be in the form of a solid or liquid and dispersion droplets. In some cases, the core material may contain a hormone receptor agonist. In some cases, the core material may contain another hormone receptor agonist or its salt. The composition of the core material can be varied, thus providing significant flexibility and enabling the effective design and development of desired microcapsule properties. Microencapsulation of substances can be carried out for several reasons. Examples include protecting reactive materials from their environment, safely and conveniently handling otherwise toxic or harmful materials, taste masking, a means for controlled or modified release properties, a means for handling liquids as solids, the preparation of free-flowing powders, and modifying the physical properties of drugs. For example, encapsulation can improve solubility and dissolution, thereby increasing the bioavailability of active ingredients such as hormone receptor agonists. Microencapsulation can be used to increase stability, improve the handling characteristics of the compound, facilitate higher bioavailability when reconstituted or administered, or any combination thereof.For example, the microencapsulated hormone receptor agonist can be made to not require refrigeration and not lose efficacy when exposed to high temperatures for a certain period of time.In some cases, the shelf life of the encapsulated hormone receptor agonist can be extended by about 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months or more compared with the liquid form containing the hormone receptor agonist.In some cases, the inhalable hormone receptor agonist can be made to not require a needle for administration.

[0161] In some cases, the core diameter of the microencapsulated particles is greater than, less than, or equal to about 100 nm (nanometers), greater than, less than, or equal to 150 nm, greater than, less than, or equal to 200 nm, greater than, less than, or equal to 250 nm, greater than, less than, or equal to 300 nm, greater than, less than, or equal to 350 nm, greater than, less than, or equal to 400 nm, or equal to 400nm, greater than 450nm, less than 450nm or equal to 450nm, greater than 500nm, less than 500nm or equal to 500nm, greater than 550nm, less than 550nm or equal to 550nm, greater than 600nm, less than 600nm or equal to 600nm, greater than 650nm, less than 650nm or equal to 650nm, greater than 700nm, less than 700nm or equal to 700nm, greater than 750nm, less than 750nm or equal to 750nm, greater than 800nm, Less than or equal to 800nm, greater than 850nm, less than 850nm, or equal to 850nm, greater than 900nm, less than 900nm, or equal to 900nm, greater than 950nm, less than 950nm, or equal to 950nm, greater than 1µm, less than 1µm, or equal to 1µm, greater than 2µm, less than 2µm, or equal to 2µm, greater than 3µm, less than 3µm, or equal to 3µm, greater than 4µm, less than 4µm, or equal to 4µm, greater than 5µm, less than 5µm, or equal to 5µm, greater than 6 μm, less than 6 μm, or equal to 6 μm; greater than 7 μm, less than 7 μm, or equal to 7 μm; greater than 8 μm, less than 8 μm, or equal to 8 μm; greater than 9 μm, less than 9 μm, or equal to 9 μm; greater than 10 μm, less than 10 μm, or equal to 10 μm; greater than 11 μm, less than 11 μm, or equal to 11 μm; greater than 12 μm, less than 12 μm, or equal to 12 μm; greater than 13 μm, less than 13 μm, or equal to 13 μm; greater than 14 μm, less than 14 μm, or equal to 14 μm;More than 15 μm, less than 15 μm, or equal to 15 μm; more than 16 μm, less than 16 μm, or equal to 16 μm; more than 17 μm, less than 17 μm, or equal to 17 μm; more than 18 μm, less than 18 μm, or equal to 18 μm; more than 19 μm, less than 19 μm, or equal to 19 μm; more than 20 μm, less than 20 μm, or equal to 20 μm; more than 21 μm, less than 21 μm, or equal to 21 μm; more than 22 μm, less than 22 μm, or equal to 22 μm; 23 μm The diameter may be greater than, less than, or equal to 23 μm, greater than, less than, or equal to 24 μm, greater than, less than, or equal to 24 μm, greater than, less than, or equal to 25 μm, greater than, less than, or equal to 25 μm, greater than, less than, or equal to 26 μm, greater than, less than, or equal to 26 μm, greater than, less than, or equal to 27 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 28 μm, greater than, less than, or equal to 29 μm, or greater than, less than, or equal to 30 μm. In some cases, the diameter of the core of the microencapsulated particles may range from about 100 nm to about 250 nm, 100 nm to about 500 nm, 100 nm to about 1 μm, 500 nm to about 1 μm, 1 μm to about 10 μm, 1 μm to about 5 μm, 2 μm to about 7 μm, 3 μm to about 8 μm, 5 μm to about 10 μm, 5 μm to about 15 μm, or 1 μm to about 30 μm. In some cases, the core may constitute about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, or 99% of the total microcapsule content (e.g., the total weight of the core and wall material). In some cases, the core may comprise about 1% to about 50%, 1% to about 20%, 1% to about 10%, 5% to about 25%, 10% to about 40%, 10% to about 60%, 20% to about 70%, 20% to about 50%, 30% to about 80%, 40% to about 90%, 50% to about 75%, or 1% to about 99% of the total microcapsule content.

[0162] In some embodiments, the microencapsulation method can include at least partially dissolving a coating material (e.g., HPMC or HPMCAS or trehalose) in a solvent, such as a mixture of ethanol and water. In some cases, particles of a hormone receptor agonist can be added to a solution of the coating material and solvent to create a suspension of particles of the hormone receptor agonist and the coating material dissolved in the solvent. In some cases, the hormone receptor agonist may not dissolve in the suspension but may remain suspended. In some cases, the hormone receptor agonist may be dissolved in the suspension. The suspension can be mixed to an at least partially uniform mixture and spray-dried. The coating can at least partially encapsulate psylocibin or a salt thereof. In some cases, the hormone receptor agonist can be amorphous. In some cases, the encapsulation of the hormone receptor agonist can be in the form of a spherical, round, oval, or any shape structure. Creation method

[0163] Also disclosed herein are methods for creating and selecting sizes of powdered pharmaceutical compositions. In some cases, formulating a composition can include mixing particles of an excipient with particles of an active agent. In some cases, formulating a composition can include creating particles of a specific size.

[0164] In some embodiments, the method for producing a powdered pharmaceutical composition can include mixing the particles described herein with an excipient.In some cases, at least a portion of the particles of the pharmaceutically acceptable excipient can have a particle size ranging from about 50 micrometers to about 200 micrometers, as measured by a particle size analyzer using laser diffraction.In some cases, at least a portion of the particles comprising the encapsulated hormone receptor agonist can have a particle size ranging from about 500 nanometers to about 15 micrometers, or from about 1 micrometer to about 20 micrometers, as measured by a particle size analyzer using laser diffraction.

[0165] In some embodiments, at least some of the particles of the pharmaceutically acceptable excipient may have a particle size ranging from about 30 μm (micrometers) to about 60 μm, 50 μm to about 200 μm, 60 μm to about 80 μm, 70 μm to about 100 μm, 90 μm to about 130 μm, 110 μm to about 150 μm, 130 μm to about 180 μm, 150 μm to about 200 μm, 190 μm to about 250 μm, or 200 μm to about 400 μm. In some cases, at least a portion of the particles of the pharmaceutically acceptable excipient are greater than or equal to about 30 μm, greater than or equal to 40 μm, greater than or equal to 45 μm, greater than or equal to 50 μm, greater than or equal to 55 μm, greater than or equal to 60 μm, greater than or equal to 65 μm, or greater than 70 μm. , or equal to 70 μm, greater than or equal to 75 μm, greater than or equal to 80 μm, greater than or equal to 80 μm, greater than or equal to 85 μm, greater than or equal to 90 μm, greater than or equal to 95 μm, greater than or equal to 100 μm, greater than or equal to 105 μm, greater than or equal to 110 μm, 1 Greater than 20 μm or equal to 120 μm, greater than 130 μm or equal to 130 μm, greater than 140 μm or equal to 140 μm, greater than 150 μm or equal to 150 μm, greater than 160 μm or equal to 160 μm, greater than 170 μm or equal to 170 μm, greater than 180 μm or equal to 180 μm, greater than 190 μm or equal to 190 μm, 200 μm greater than or equal to 200 μm, greater than or equal to 210 μm, greater than or equal to 220 μm, greater than or equal to 220 μm, greater than or equal to 230 μm, greater than or equal to 230 μm, greater than or equal to 240 μm, greater than or equal to 250 μm, greater than or equal to 250 μm, greater than or equal to 260 μm, greater than or equal to 260 μm, greater than or equal to 270 μm, greater than 280 μm,or equal to 280 μm, greater than or equal to 290 μm, greater than or equal to 300 μm, greater than or equal to 310 μm, greater than or equal to 320 μm, greater than or equal to 330 μm, greater than or equal to 340 μm, greater than or equal to 350 μm, greater than or equal to 360 μm, greater than or equal to 370 μm, greater than or equal to 380 μm, greater than or equal to 390 μm, or greater than or equal to 400 μm. In some cases, at least a portion of the particles of the pharmaceutically acceptable excipient are less than about 30 μm, less than 40 μm, less than 45 μm, less than 50 μm, less than 55 μm, less than 60 μm, less than 65 μm, less than 70 μm, less than 75 μm, less than 80 μm, less than 85 μm, less than 90 μm, less than 95 μm, less than 100 μm, less than 105 μm, less than 110 μm, less than 120 μm, less than 130 μm, less than 140 μm, less than 150 μm, less than 160 μm, or less than 170 μm. The particle size may be less than 180 μm, less than 190 μm, less than 200 μm, less than 210 μm, less than 220 μm, less than 230 μm, less than 240 μm, less than 250 μm, less than 260 μm, less than 270 μm, less than 280 μm, less than 290 μm, less than 300 μm, less than 310 μm, less than 320 μm, less than 330 μm, less than 340 μm, less than 350 μm, less than 360 μm, less than 370 μm, less than 380 μm, less than 390 μm, or less than 400 μm. In some cases, the particles of the pharmaceutically acceptable excipient may range from about 50 μm to about 100 μm, which may be preferable for inhalation or nasal administration for deposition in the oropharynx. In some cases, particle size may include the diameter, radius, or length of the particle. In some cases, particle size may be a measure of the mean, median, or mode of a plurality of particles.

[0166] With respect to particle size, in certain cases, particles can be measured by their aerodynamic diameter. ae) is the equivalent spherical diameter, derived based on the equivalence of an inhaled particle to a sphere of unit density (ρo) settling at the same velocity according to the following formula: D ae =D v √(ρ / χρo), where Dv is the volume-equivalent diameter, ρ is the particle density, and χ is the shape factor. Thus, the aerodynamic behavior depends on the particle geometry, density, and volume diameter: small spherical particles with high density behave aerodynamically as larger particles and are less likely to be transported to the lower respiratory tract. By reducing the volume diameter and density of the particles by different processes or by increasing the shape factor, D ae can be improved.

[0167] For pharmaceutical formulations administered as an aerosol. An "aerosol" can be a suspension of liquid and solid particles produced by an aerosol generating device, such as a small volume nebulizer (SVN), pressurized metered dose inhaler (pMDI), or dry powder inhaler (DPI). "Aerosol deposition" can be the process by which aerosol particles deposit on an absorbent surface. An "aerosol generating device" can be the device used to generate the aerosol particles. "Aerosol output" can be the mass of medication that leaves the aerosol generating device. "Aerosol therapy" can be the delivery of a solid or liquid aerosol.

[0168] In some embodiments, i) particles of an active ingredient (e.g., a hormone receptor agonist) or a pharmaceutically acceptable salt thereof, or ii) particles comprising at least a partially encapsulated active ingredient or a pharmaceutically acceptable salt thereof, may have a particle size ranging from about 100 nm (nanometers) to about 500 nm, 300 nm to about 800 nm, 700 nm to about 1.2 μm, 1 μm to about 3 μm, 2 μm to about 4 μm, 3 μm to about 6 μm, 5 μm to about 8 μm, 6 μm to about 9 μm, 7 μm to about 10 μm, 8 μm to about 11 μm, 9 μm to about 13 μm, 10 μm to about 15 μm, 12 μm to about 20 μm, 14 μm to about 25 μm, or 18 μm to about 30 μm. In some cases, i) particles of the active ingredient or a pharmaceutically acceptable salt thereof or ii) particles comprising at least a partially encapsulated active ingredient or a pharmaceutically acceptable salt thereof are less than about 30 nm, less than 50 nm, less than 60 nm, less than 70 nm, less than 80 nm, less than 90 nm, less than 100 nm, less than 150 nm, less than 200 nm, less than 250 nm, less than 300 nm, less than 350 nm, less than 400 nm, less than 450 nm, less than 500 nm, less than 550 nm, less than 600 nm, less than 650 nm, less than 700 nm, less than 750 nm, less than 800 nm In some embodiments, the particle size may be less than 850 nm, less than 900 nm, less than 950 nm, less than 1 μm, less than 2 μm, less than 3 μm, less than 4 μm, less than 5 μm, less than 6 μm, less than 7 μm, less than 8 μm, less than 9 μm, less than 10 μm, less than 11 μm, less than 12 μm, less than 13 μm, less than 14 μm, less than 15 μm, less than 16 μm, less than 17 μm, less than 18 μm, less than 19 μm, less than 20 μm, less than 21 μm, less than 22 μm, less than 23 μm, less than 24 μm, less than 25 μm, less than 26 μm, less than 27 μm, less than 28 μm, less than 29 μm, or less than 30 μm. In some cases, the particles of i) the active ingredient or a pharmaceutically acceptable salt thereof or ii) the particles comprising at least a partially encapsulated active ingredient or a pharmaceutically acceptable salt thereof are greater than or equal to about 30 nm, greater than or equal to 50 nm, greater than or equal to 60 nm, greater than or equal to 70 nm, greater than or equal to 80 nm,Greater than or equal to 90nm, greater than or equal to 100nm, greater than or equal to 150nm, greater than or equal to 200nm, greater than or equal to 250nm, greater than or equal to 300nm, greater than or equal to 350nm, greater than or equal to 400nm, greater than or equal to 450nm, greater than or equal to 500nm, greater than or equal to 550nm greater than or equal to 600nm, greater than or equal to 600nm, greater than or equal to 650nm, greater than or equal to 700nm, greater than or equal to 750nm, greater than or equal to 800nm, greater than or equal to 850nm, greater than or equal to 850nm, greater than or equal to 900nm, greater than or equal to 950nm, greater than or equal to 1µm, greater than or equal to 2µm, greater than or equal to 3µm, Greater than or equal to 4 μm, greater than or equal to 5 μm, greater than or equal to 6 μm, greater than or equal to 7 μm, greater than or equal to 8 μm, greater than or equal to 9 μm, greater than or equal to 10 μm, greater than or equal to 11 μm, greater than or equal to 12 μm, greater than or equal to 13 μm, greater than or equal to 14 μm, greater than or equal to 15 μm, greater than 16 μm greater than or equal to 16 μm, greater than or equal to 17 μm, greater than or equal to 18 μm, greater than or equal to 19 μm, greater than or equal to 20 μm, greater than or equal to 21 μm, greater than or equal to 22 μm, greater than or equal to 23 μm, greater than or equal to 24 μm, greater than or equal to 25 μm, greater than or equal to 26 μm, greater than or equal to 27 μm,The particle size may be greater than or equal to 28 μm, greater than or equal to 29 μm, or greater than or equal to 30 μm. In some cases, particles of i) the active ingredient or a pharmaceutically acceptable salt thereof or ii) particles comprising at least a partially encapsulated active ingredient or a pharmaceutically acceptable salt thereof may be about 1 μm to about 5 μm, which may be preferable when administered by inhalation or intranasally for absorption into the alveoli.

[0169] In some embodiments, the particles or compositions described herein have a density of about 0.1 grams per centimeter (g / cm 3 ) exceeding 0.2g / cm 3 Exceeds 0.3g / cm 3 Exceeds 0.4g / cm 3 More than 0.5g / cm 3 Exceeds 0.6g / cm 3 Exceeds 0.7g / cm 3 Exceeds 0.8g / cm 3 Exceeds 0.9g / cm 3 Exceeds 1.0g / cm 3 Exceeds 1.1g / cm 3 or more than 1.2 g / cm 3 In some embodiments, the particles described herein may have a tap density of greater than about 0.1 g / cm 3 Less than 0.2g / cm 3 Less than 0.3g / cm 3 Less than 0.4g / cm 3 Less than 0.5g / cm 3 Less than 0.6g / cm 3 Less than 0.7g / cm 3 Less than 0.8g / cm 3 Less than 0.9g / cm 3 Less than 1.0 g / cm 3 Less than 1.1g / cm 3 Less than or equal to 1.2 g / cm 3 In some cases, the particles or compositions described herein may have a tap density of less than about 0.6 g / cm 3 or more than 0.7 g / cm 3In some cases, the particles or compositions described herein may have a tap density of greater than about 0.6 g / cm 3 or 0.7 g / cm 3 The tap density of a powder may be a ratio of the powder's mass to the volume it occupies after tapping for a specified time. In some cases, the tap density may be a measure of the envelope mass density that characterizes the particle. The envelope mass density of a statistically isotropically shaped particle may be defined as the particle's mass divided by the smallest spherical envelope volume that can contain the particle. Features that may contribute to low tap density include irregular surface texture, porous structure, or a combination thereof. Tap density can be measured using equipment known to those skilled in the art, such as a Dual Platform Microprocessor Controlled Tap Density Tester (Vankel, NC) or a GeoPyc™ instrument (Micrometrics Instrument Corp., Norcross, Ga.).

[0170] In some embodiments, the sizes of particles of the active ingredient or a pharmaceutically acceptable salt thereof can be mixed. In some cases, mixing sizes can change the release time of the drug. For example, small particles (e.g., about 1 μm to about 5 μm) can be easily absorbed into the bloodstream, while particles larger than about 10 μm can take longer to be absorbed into the bloodstream. In some cases, particles with a diameter of about 1 μm to about 10 μm can be inhaled into the lungs, while larger particles can be deposited in the oropharynx. In some cases, particles with a diameter of about 1 μm to about 5 μm can be absorbed more quickly than particles with a diameter of about 7 μm to about 10 μm. In some embodiments, particles with a size of about 7 μm to about 10 μm can be mixed with particles with a size of about 1 μm to about 5 μm. In some embodiments, the weight ratio of particles having a diameter of about 7 μm to about 10 μm to particles having a size of about 1 μm to about 5 μm is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 to about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:8, from about 1:1 to about 1:10, from about 1:2 to about 1:3, from about 1:2 to about 1:4, from about 1:2 to about 1:5, from about 1:1 to about 1:8 1:2 to about 1:8, about 1:2 to about 1:10, about 1:3 to about 1:4, about 1:3 to about 1:5, about 1:3 to about 1:8, about 1:3 to about 1:10, about 1:4 to about 1:5, about 1:4 to about 1:8, about 1:4 to about 1:10, about 1:5 to about 1:8, about 1:5 to about 1:10, or 1:8 to about 1:10.In some embodiments, the weight ratio of particles having a diameter of about 1 μm to about 5 μm to particles having a size of about 7 μm to about 10 μm is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 to about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:8, from about 1:1 to about 1:10, from about 1:2 to about 1:3, from about 1:2 to about 1:4, from about 1:2 to about 1:5, from about 1:1 to about 1:8, from about 1:1 to about 1:10, from about 1:2 to about 1:3, from about 1:2 to about 1:4, from about 1:2 to about 1:5, from about 1:1 to about 1:10 ... The ratio may range from about 1:2 to about 1:8, about 1:2 to about 1:10, about 1:3 to about 1:4, about 1:3 to about 1:5, about 1:3 to about 1:8, about 1:3 to about 1:10, about 1:4 to about 1:5, about 1:4 to about 1:8, about 1:4 to about 1:10, about 1:5 to about 1:8, about 1:5 to about 1:10, or 1:8 to about 1:10. In some embodiments, larger sized particles (about 10 μm to about 20 μm) can be mixed with smaller sized particles (about 1 μm to about 10 μm). In some embodiments, the weight ratio of larger sized particles (about 10 μm to about 20 μm) to smaller sized particles (about 1 μm to about 10 μm) is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 to about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:8, from about 1:1 to about 1:10, from about 1:2 to about 1:3, from about 1:2 to about 1:4, from about 1:2 to about The ratio may range from about 1:5, from about 1:2 to about 1:8, from about 1:2 to about 1:10, from about 1:3 to about 1:4, from about 1:3 to about 1:5, from about 1:3 to about 1:8, from about 1:3 to about 1:10, from about 1:4 to about 1:5, from about 1:4 to about 1:8, from about 1:4 to about 1:10, from about 1:5 to about 1:8, from about 1:5 to about 1:10, or from 1:8 to about 1:10.In some embodiments, the weight ratio of smaller sized particles (about 1 μm to about 10 μm) to larger sized particles (about 10 μm to about 20 μm) is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 to about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:8, from about 1:1 to about 1:10, from about 1:2 to about 1:3, from about 1:2 to about 1:4, from about 1:2 to about The ratio may range from about 1:5, from about 1:2 to about 1:8, from about 1:2 to about 1:10, from about 1:3 to about 1:4, from about 1:3 to about 1:5, from about 1:3 to about 1:8, from about 1:3 to about 1:10, from about 1:4 to about 1:5, from about 1:4 to about 1:8, from about 1:4 to about 1:10, from about 1:5 to about 1:8, from about 1:5 to about 1:10, or from 1:8 to about 1:10.

[0171] In some embodiments, active ingredient particles can be prepared by spray drying.In some cases, encapsulated active ingredient particles can be prepared by spray drying.In some cases, active ingredient particles can be prepared by other methods.In some cases, active ingredient particles can be prepared by air jet atomization, spiral crushing, controlled precipitation, high-pressure homogenization or freeze-grinding.

[0172] In some cases, the microencapsulated particles herein may have one or more coatings (e.g., shells). For example, the active ingredient may include one, two, three, four, five, six, seven, eight, nine, or more than nine coating layers. In some embodiments, the encapsulated active ingredient particles may be processed in a fluidized bed to apply one or more additional coatings. For example, the encapsulated active ingredient particles may be processed in a fluidized bed to apply an outer enteric coating.

[0173] In some embodiments, particles that are not pharmaceutically acceptable excipients can have a particle size ranging from about 1 μm to about 20 μm. In some embodiments, particle size can be measured by a particle analyzer using laser diffraction (LD), static light scattering, dynamic light scattering (DLS), or nanoparticle tracking analysis (NTA).

[0174] In some embodiments, the active ingredient particles may contain a hormone receptor agonist drug, such as a hormone receptor agonist. In some cases, the hormone receptor agonist may be mixed with an excipient such as lactose or its salt. In some cases, the excipient may include lactose, microcrystalline cellulose, cellulose, mannitol, sorbitol, starch, starch glycolate, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, cyclodextrin, maltodextrin, croscarmellose sodium, corn starch, carrageenan, sorbitol, maltitol, glucose, any pharmaceutically acceptable salt thereof, or any combination thereof.

[0175] In some cases, the encapsulated or unencapsulated hormone receptor agonist or salt thereof may be greater than, less than, or equal to about 30 nm, greater than, less than, or equal to 50 nm, greater than, less than, or equal to 60 nm, greater than, less than, or equal to 70 nm, greater than, less than, or equal to 80 nm, greater than, less than, or equal to 90 nm, greater than, less than, or equal to 100 nm. greater than, less than, or equal to 150nm; greater than, less than, or equal to 150nm; greater than, less than, or equal to 200nm; greater than, less than, or equal to 200nm; greater than, less than, or equal to 250nm; greater than, less than, or equal to 300nm; greater than, less than, or equal to 300nm; greater than, less than, or equal to 350nm; greater than, less than, or equal to 400nm; greater than, less than, or equal to 400nm; greater than, less than, or equal to 450nm; greater than, less than, or equal to 500nm; or equal to 500nm, greater than 550nm, less than 550nm or equal to 550nm, greater than 600nm, less than 600nm or equal to 600nm, greater than 650nm, less than 650nm or equal to 650nm, greater than 700nm, less than 700nm or equal to 700nm, greater than 750nm, less than 750nm or equal to 750nm, greater than 800nm, less than 800nm ​​or equal to 800nm, greater than 850nm, less than 850nm or equal to 850nm, greater than 900nm, 90 less than 0 nm or equal to 900 nm, greater than 950 nm or less than 950 nm or equal to 950 nm, greater than 1 μm or less than 1 μm or equal to 1 μm, greater than 2 μm or less than 2 μm or equal to 2 μm, greater than 3 μm or less than 3 μm or equal to 3 μm, greater than 4 μm or less than 4 μm or equal to 4 μm, greater than 5 μm or less than 5 μm or equal to 5 μm, greater than 6 μm or less than 6 μm or equal to 6 μm, greater than 7 μm or less than 7 μm or equal to 7 μm, greater than 8 μm or less than 8 μm,or equal to 8 μm, greater than 9 μm, less than 9 μm, or equal to 9 μm, greater than 10 μm, less than 10 μm, or equal to 10 μm, greater than 11 μm, less than 11 μm, or equal to 11 μm, greater than 12 μm, less than 12 μm, or equal to 12 μm, greater than 13 μm, less than 13 μm, or equal to 13 μm, greater than 14 μm, less than 14 μm, or equal to 14 μm, 1 It may have an average particle size of greater than 5 μm, less than or equal to 15 μm, greater than 16 μm, less than or equal to 16 μm, greater than 17 μm, less than or equal to 17 μm, greater than 18 μm, less than or equal to 18 μm, greater than 19 μm, less than or equal to 19 μm, or greater than 20 μm, less than or equal to 20 μm. In some cases, the excipient or salt thereof has a diameter of greater than, less than, or equal to about 30 μm, greater than, less than, or equal to 40 μm, greater than, less than, or equal to 40 μm, greater than, less than, or equal to 45 μm, greater than, less than, or equal to 50 μm, greater than, less than, or equal to 50 μm, greater than, less than, or equal to 55 μm, greater than, less than, or equal to 60 μm, greater than, less than, or equal to 60 μm, greater than, less than, or equal to 65 μm, greater than, less than, or equal to 70 μm, greater than, less than, or equal to 70 μm, greater than, less than, or equal to 75 μm, greater than, less than, or equal to 80 μm, less than, or equal to 80 μm, or 85 μm. greater than, less than or equal to 85 μm, greater than 90 μm, less than 90 μm, or equal to 90 μm, greater than 95 μm, less than 95 μm, or equal to 95 μm, greater than 100 μm, less than 100 μm, or equal to 100 μm, greater than 105 μm, less than 105 μm, or equal to 105 μm, greater than 110 μm, less than 110 μm, or equal to 110 μm, greater than 115 μm, less than 115 μm, or equal to 115 μm, greater than 120 μm, less than 120 μm, greater than 125 μm, less than 125 μm, or equal to 125 μm, greater than 130 μm, less than 130 μm, or equal to 130 μm, greater than 135 μm,Less than or equal to 135 μm, greater than 140 μm, less than 140 μm or equal to 140 μm, greater than 145 μm, less than 145 μm or equal to 145 μm, greater than 150 μm, less than 150 μm or equal to 150 μm, greater than 155 μm, less than 155 μm or equal to 155 μm, greater than 160 μm, less than 160 μm or equal to 160 μm, greater than 165 μm, Less than or equal to 165 μm, greater than 170 μm, less than 170 μm or equal to 170 μm, greater than 175 μm, less than 175 μm or equal to 175 μm, greater than 180 μm, less than 180 μm or equal to 180 μm, greater than 185 μm, less than 185 μm or equal to 185 μm, greater than 190 μm, less than 190 μm or equal to 190 μm, greater than 195 μm, Less than 95 μm or equal to 195 μm, greater than 200 μm, less than 200 μm or equal to 200 μm, greater than 205 μm, less than 205 μm or equal to 205 μm, greater than 210 μm, less than 210 μm or equal to 210 μm, greater than 215 μm, less than 215 μm or equal to 215 μm, greater than 220 μm, less than 220 μm or equal to 220 μm, greater than 225 μm, 2 The average particle size may be less than 25 μm or equal to 225 μm, greater than 230 μm, less than 230 μm or equal to 230 μm, greater than 235 μm, less than 235 μm or equal to 235 μm, greater than 240 μm, less than 240 μm or equal to 240 μm, greater than 245 μm, less than 245 μm or equal to 245 μm, or greater than 250 μm, less than 250 μm or equal to 250 μm. In some cases, the shell of the microencapsulated particles comprises HPMCAS or HPMC. In some cases, the shell of the microencapsulated particles may comprise trehalose. In some cases, microencapsulation of hormone receptor agonists with HPMCAS can result in faster absorption into the lungs. For example, hormone receptor agonists may not be water-soluble, and by microencapsulating them with HPMCAS,This can result in increased absorption from the lungs into the bloodstream. In some cases, microencapsulation can increase the solubility of the active ingredient. In some cases, the microencapsulated hormone receptor agonist can be absorbed about 10% to about 70%, 5% to about 10%, 5% to about 20%, 10% to about 30%, 15% to about 40%, 25% to about 40%, 35% to about 50%, 10% to about 60%, 40% to about 90%, or 20% to about 50% faster than the non-microencapsulated hormone receptor agonist. In some cases, the microencapsulated hormone receptor agonist may be absorbed into the bloodstream about 5 seconds to about 30 seconds, 5 seconds to about 20 seconds, 10 seconds to about 20 seconds, 10 seconds to about 30 seconds, 10 seconds to about 60 seconds, 20 seconds to about 40 seconds, 30 seconds to about 60 seconds, 30 seconds to about 2 minutes, 1 minute to about 2 minutes, or 1 minute to 5 minutes after inhalation.

[0176] In some cases, hormone receptor agonist or its salt can be mixed with excipients before being added to capsules.In some cases, mixing can include blending in a blender such as a V-type blender.In some cases, hormone receptor agonist can be mixed with excipients in a V-type blender.V-type blenders can include Patterson Kelly / PK Blender, Gemco or Ross blender.In some cases, blending can be high-shear blending or low-shear blending.In some cases, blending can be high-speed blending or low-speed blending.In some cases, blending can make hormone agonist or its salt and excipients evenly distributed. In some cases, the weight ratio of the hormone agonist or salt thereof to the excipient is about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1 , 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, or 100:1 (hormone agonist to vehicle). In some cases, the weight ratio of the hormone agonist or salt thereof to the excipient is about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, 1:80, 1:85, 1:90, 1:95,Or 1:100 (hormone agonist to excipient). In some embodiments, the active ingredient or a pharmaceutically acceptable salt thereof (e.g., testosterone or a pharmaceutically acceptable salt thereof) may comprise at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% by weight of the pharmaceutical composition. The admixture may not cause the excipient particles to be coated with the hormone agonist particles or a salt thereof. In some cases, the hormone receptor agonist, e.g., testosterone or a pharmaceutically acceptable salt thereof, and the excipient can be administered by inhalation using a dry powder inhaler. In some cases, the dry powder inhaler does not contain a propellant. In some cases, the dry powder inhaler does not contain a chlorofluorocarbon, a hydrofluorocarbon, a fluorocarbon, or any combination thereof as a propellant. In some cases, the dry powder inhaler is not pressurized. In some cases, the inhaler may contain a propellant. In some cases, the bioavailability of the hormone receptor agonist resulting from inhaled administration of the hormone agonist or a salt thereof and excipients may be about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%. In some cases, the Tmax (e.g., the time it takes to reach the peak concentration of drug in the plasma) of the hormone receptor agonist can be about 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes, 65 minutes, 70 minutes, 75 minutes, 80 minutes, 85 minutes, 90 minutes, 95 minutes, 100 minutes, 105 minutes, 110 minutes, 115 minutes, 120 minutes, 130 minutes, 140 minutes, 150 minutes, 160 minutes, 170 minutes, 180 minutes, 190 minutes, 200 minutes, 210 minutes, 220 minutes, 230 minutes, 240 minutes, 250 minutes, 260 minutes, 270 minutes, 280 minutes, 290 minutes, or 300 minutes. In some cases, the composition may comprise a hormone receptor agonist at greater than, less than, or equal to about 10 μg, greater than, less than, or equal to 25 μg, greater than, less than, or equal to 50 μg, greater than, less than, or equal to 75 μg, greater than, less than, or equal to 75 μg, greater than, less than, or equal to 100 μg,or equal to 100 μg, greater than 150 μg, less than 150 μg or equal to 150 μg, greater than 200 μg, less than 200 μg or equal to 200 μg, greater than 220 μg, less than 220 μg or equal to 220 μg, greater than 250 μg, less than 250 μg or equal to 250 μg, greater than 300 μg, less than 300 μg or equal to 300 μg, greater than 350 μg, less than 350 μg or equal to 350 μg, greater than 400 μg, less than 400 μg or equal to 400 μg, greater than 450 μg, Less than or equal to 450 μg, more than 500 μg, less than or equal to 500 μg, more than 550 μg, less than 550 μg, more than 600 μg, less than or equal to 600 μg, more than 650 μg, less than or equal to 650 μg, more than 700 μg, less than or equal to 700 μg, more than 750 μg, less than or equal to 750 μg, more than 800 μg, less than or equal to 800 μg, 850 greater than μg, less than or equal to 850 μg, greater than 900 μg, less than 900 μg, or equal to 900 μg, greater than 950 μg, less than 950 μg, or equal to 950 μg, greater than 1000 μg, less than 1000 μg, or equal to 1000 μg, greater than 2 mg, less than 2 mg, or equal to 2 mg, greater than 3 mg, less than 3 mg, or equal to 3 mg, greater than 4 mg, less than 4 mg, or equal to 4 mg, greater than 5 mg, less than 5 mg, or equal to 5 mg, greater than 6 mg, less than 6 mg, if or equal to 6 mg, more than 7 mg, less than 7 mg, or equal to 7 mg, more than 8 mg, less than 8 mg, or equal to 8 mg, more than 9 mg, less than 9 mg, or equal to 9 mg, more than 10 mg, less than 10 mg, or equal to 10 mg, more than 11 mg, less than 11 mg, or equal to 11 mg, more than 12 mg, less than 12 mg, or equal to 12 mg, more than 13 mg, less than 13 mg, or equal to 13 mg, more than 14 mg, less than 14 mg, or equal to 14 mg, more than 15 mg, less than 15 mg,or equal to 15 mg, greater than 16 mg, less than 16 mg, or equal to 16 mg, greater than 17 mg, less than 17 mg, or equal to 17 mg, greater than 18 mg, less than 18 mg, or equal to 18 mg, greater than 19 mg, less than 19 mg, or equal to 19 mg, greater than 20 mg, less than 20 mg, or equal to 20 mg, greater than 21 mg, less than 21 mg, or equal to 21 mg, greater than 22 mg, less than 22 mg, or equal to 22 mg, greater than 23 mg, less than 23 mg, or equal to 23 mg, greater than 24 mg, less than 24 mg, or equal to 24 mg, or greater than 25 mg, less than 25 mg, or equal to 25 mg.

[0177] In some embodiments, a method for producing a powdered pharmaceutical composition can include blending i) particles of a pharmaceutically acceptable excipient and ii) a plurality of spray-dried particles. In some cases, each particle of the plurality of spray-dried particles can include a hormone receptor agonist, such as testosterone or a pharmaceutically acceptable salt thereof. In some cases, the hormone receptor agonist can be substantially encapsulated with a coating material. In some cases, some of the plurality of spray-dried particles including a hormone receptor agonist or a pharmaceutically acceptable salt thereof substantially encapsulated with a coating material can have a particle size ranging from about 1 micrometer to about 10 micrometers, or from about 1 micrometer to about 5 micrometers, as measured by a particle analyzer using laser diffraction. In some cases, the coating material can include trehalose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cyclodextrin, maltodextrin, povidone, copovidone, or any combination thereof.

[0178] In some embodiments, the powdered pharmaceutical composition can be made by a process comprising: a) contacting particles comprising a hormone receptor agonist (e.g., testosterone or a pharmaceutically acceptable salt thereof), a coating material, and a solvent; and b) spray-drying the mixed particles comprising the hormone receptor agonist, the coating material, and the solvent. In some cases, the spray-dried particles can be mixed or blended with a pharmaceutically acceptable excipient to create the powdered pharmaceutical composition. Encapsulation of powdered pharmaceutical compositions

[0179] In some embodiments, the pharmaceutical composition can be contained in a capsule, a capsule-in-capsule, a tablet, a gel, a gummy, a spray, an ointment, a paste, a jelly, an oil, a tincture, a lotion, a cream, a balm, a food, a drink, a liquid, a syrup, or any combination thereof. In some cases, the gummy can include corn syrup, sucrose, glucose syrup, sugar, gelatin, starch, water, sucralose, fructose, glucose, allulose, maltose, a sugar alcohol, aspartame, xylitol, stevia, galactose, saccharin, pectin, carrageenan, a flavoring (e.g., berry flavor, natural flavor, apple flavor, cherry flavor, watermelon flavor, strawberry flavor), or any combination thereof. In some cases, gummies may include ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, maltotetritoitol, polyglycitol, or any combination thereof. In some cases, gummies may include pectin. In some cases, gummies may include gelatin. In some cases, gummies may include carrageenan. In some cases, the at least partially encapsulated particles may be substantially uniform throughout the gummies.

[0180] In some embodiments, the capsule may comprise a one-piece capsule, a two-piece capsule, a transparent capsule, an opaque capsule, an opaque capsule, a slow-release capsule, an extended-release capsule, a standard-release capsule, a rapid-release capsule, an immediate-release capsule, a hard-shell capsule, a soft gel capsule, a gel capsule, a hard gelatin capsule, a soft gelatin capsule, an animal-derived capsule, a vegetable capsule, a polysaccharide capsule, a cellulose capsule, a mucopolysaccharide capsule, a tapioca capsule, a hydroxypropyl methylcellulose (HPMC) capsule, a pullulan capsule, an enteric-coated capsule, an uncoated capsule, a coated capsule, a titanium dioxide-containing capsule, a fatty acid-containing capsule, a wax-containing capsule, a shellac-containing capsule, a plastic-containing capsule, a plasticizer-containing capsule, a glycerin-containing capsule, a sorbitol-containing capsule, a plant fiber-containing capsule, an additive-containing capsule, a preservative-containing capsule, a colorant-containing capsule, or any combination thereof.

[0181] In some embodiments, the capsule size can be adjusted according to the requirements of the pharmaceutical composition. In some embodiments, the capsule size is 000, 00, 0, 1, 2, 3, or 4. In some embodiments, the capsule size can be 000. In some embodiments, the capsule size can be 00. In some embodiments, the capsule size can be 0. In some embodiments, the capsule size can be 1. In some embodiments, the capsule size can be 2. In some embodiments, the capsule size can be 3. In some embodiments, the capsule size can be 4. In some embodiments, the capsule volume ranges from about 0.21 ml to about 1.37 ml.

[0182] In some embodiments, a capsule band can be added to the capsule. In some cases, capsule banding can be a process of sealing a capsule so that it can be filled with liquid, powder, or other types of ingredients. In some cases, a sealed joint may exist between the capsule cap and body, and therefore, an additional band may need to be applied to prevent the drug from leaking out of the capsule. In some cases, the additional band may provide a tamper-evident band that can reduce oxidation and minimize any odors. In some cases, banding can be applied using a banding machine, in which a thin layer of HPMC (hydroxypropyl methylcellulose) is applied as the capsule passes through two rollers that apply the banding material to the capsule. In this process, the banding material can be heated and the temperature can be controlled to create a smooth, liquid-tight band that joins the top and body of the capsule. This can provide a visual tamper-evident barrier to the capsule.

[0183] In some embodiments, the powdered pharmaceutical compositions described herein, when stored in a sealed container at about 20° C., 25° C., or 30° C. and room air at a relative humidity of about 40 percent, 45 percent, 50 percent, 55 percent, or 60 percent, retain at least about 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the active ingredient or a salt thereof as measured by HPLC after 4 months, 6 months, 12 months, or 24 months.

[0184] In some embodiments, the pharmaceutical composition can be contained in a capsule. The capsule can be filled with the powdered pharmaceutical composition to about 25% to about 75% of its volume. In some cases, the capsule can be filled with the pharmaceutical composition described herein to a volume of more than, less than, or equal to about 30%, more than, less than, or equal to 31%, more than, less than, or equal to 32%, more than, less than, or equal to 33%, more than, less than, or equal to 34%, more than, less than, or equal to 35%, more than, less than, or equal to 36%, more than, less than, or equal to 37%, more than, less than, or equal to 38%, more than, less than, or equal to 39%, or more than, less than, or equal to 40% of its volume. In some embodiments, the volume of the capsule is about 25% to about 30%, about 25% to about 40%, about 25% to about 50%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 25% to about 75%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 30% to about 75%, about 40% to about 50 ... The powdered pharmaceutical composition can be filled to about 60%, about 40% to about 65%, about 40% to about 70%, about 40% to about 75%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 50% to about 75%, about 60% to about 65%, about 60% to about 70%, about 60% to about 75%, about 65% to about 70%, about 65% to about 75%, or 70% to about 75%.

[0185] In some embodiments, the total capsule contents contain less than about 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% by weight of water, or less than about 50%, 40%, 30%, 25%, 20%, 10%, 5%, or 1% by weight of water.

[0186] In some embodiments, the total content of all gases in the capsule can be less than about 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% water by weight. In some embodiments, the total content of all gases in the capsule can be less than about 50%, 40%, 30%, 25%, 20%, 10%, 5%, or 1% water by weight.

[0187] In some embodiments, the capsule further comprises an inert gas in the volume not occupied by the powdered pharmaceutical composition. In some embodiments, the inert gas comprises an elemental gas, a compound gas, a noble gas, helium, neon, argon, krypton, xenon, a noble gas compound, purified argon, purified nitrogen, nitrogen, sulfur hexafluoride, or any combination thereof. In some embodiments, the inert gas comprises nitrogen. In some cases, the inert gas in the capsule may comprise at least about 75%, 80%, 85%, 90%, or 95% gas by volume.

[0188] In some embodiments, the pharmaceutical composition can be contained in a capsule, wherein the capsule can be at least partially contained within a device that can be a drug delivery device, an inhalation drug delivery device, a diffuser, an inhaler, a metered dose inhaler, a dry powder inhaler, a soft mist inhaler, or any combination thereof. In some embodiments, the device can be an inhaler. In some cases, the dry powder inhaler does not contain a propellant. In some cases, the dry powder inhaler may not be pressurized. In some cases, a method of using a dry powder inhaler includes inhaling or inhaling the active ingredient or composition into the lungs. In some cases, the dry powder inhaler can be breath-actuated, and when a subject inhales through the inhaler, the inhaler releases particles (e.g., active ingredient, excipients, or both), which travel throughout the respiratory system. In some cases, a capsule can contain the active ingredient, and the capsule is punctured to release the particles prior to inhalation by the dry powder inhaler. In some cases, particle size and aerodynamic properties can affect travel throughout the respiratory system.

[0189] In some aspects, the pharmaceutical composition can be contained in a capsule, where the capsule can be at least partially contained within a device. In some aspects, the pharmaceutical composition can be contained in a capsule, where the capsule can be at least partially contained within a device, where the device contains a sharp surface configured to puncture or slice the capsule. In some aspects, the pharmaceutical composition can be contained in a capsule, where the capsule can be at least partially contained within a device, where the device contains a sharp surface configured to puncture or slice the capsule, where the device can be manipulated prior to administration such that the capsule is punctured or sliced ​​by the sharp surface.

[0190] In some aspects, the pharmaceutical composition can be contained in a capsule, where the capsule can be at least partially contained within an inhaler, where the inhaler contains a sharp surface configured to puncture or slice the capsule. In some aspects, the pharmaceutical composition can be contained in a capsule, where the capsule can be at least partially contained within an inhaler, where the inhaler contains a sharp surface configured to puncture or slice the capsule, and the inhaler can be operated so that the sharp surface punctures or slices the capsule prior to administration. In some aspects, the inhaler unit can be reused by a process that includes replacing a consumed capsule with a new capsule containing the powdered pharmaceutical composition. In some aspects, a component of the inhaler unit configured to at least partially retain the capsule can be temporarily at least partially separable from the inhaler unit. In some aspects, the capsule can be at least partially visible through an at least partially transparent material present in the inhaler unit.

[0191] Also disclosed herein is a kit comprising a pharmaceutical composition at least partially contained in an enclosure or container. Also disclosed herein is a method for producing a kit comprising a pharmaceutical composition at least partially contained in an enclosure or container. In some cases, the container may comprise a plastic container, a metal container, a wooden container, a glass container, or a combination thereof.

[0192] In some cases, the compositions can be packaged to provide a nominal fill weight of about 3 mg to 30 mg. Based on the aerosol performance characteristics and the concentration of the active agent in the dry powder composition, the compositions can be packaged to provide a delivered dose of at least about 0.1 mg to about 20 mg, at least about 0.25 mg to about 20 mg, at least about 0.5 mg to about 10 mg, at least about 0.25 mg to about 5 mg, or at least about 0.25 mg to about 3 mg. In some cases, the compositions can be packaged to provide a delivered dose of at least about 0.1 mg, about 0.25 mg, about 0.5 mg, about 1 mg, about 5 mg, about 10 mg, about 15 mg, or about 20 mg. In some cases, the composition can be encapsulated to provide a delivered dose of about 0.25 mg to about 20 mg, including delivered doses in the ranges of about 0.25 mg to about 5 mg, about 0.25 mg to about 2 mg, about 0.25 mg to about 3 mg, about 0.25 mg to about 4 mg, about 1 mg to about 5 mg, about 2 mg to about 8 mg, about 2 mg to about 12 mg, and about 5 mg to about 15 mg. In some cases, the composition can be encapsulated to provide a delivered dose in the range of about 0.25 mg to about 5 mg, about 0.25 mg to about 2 mg, about 0.25 mg to about 3 mg, about 0.25 mg to about 4 mg, about 1 mg to about 5 mg, about 2 mg to about 8 mg, about 2 mg to about 12 mg, or about 5 mg to about 15 mg. Delivery of pharmaceutical compositions

[0193] In some embodiments, administration of the pharmaceutical composition or second therapeutic agent may be orally, nasally, intraocularly, anally, by injection, intravenously, intramuscularly, subcutaneously, intraperitoneally, transdermally, by inhalation, or any combination thereof.

[0194] In some embodiments, administration of the pharmaceutical composition may be by inhalation. In some embodiments, inhalation may be oral inhalation, nasal administration, or any combination thereof. In some embodiments, the powdered pharmaceutical composition may be inhaled into a human lung. In some cases, inhalation may be through the mouth, for example, using a dry powder inhaler. In some cases, at least a portion of the excipient may be deposited in the oropharynx. In some embodiments, the powdered pharmaceutical composition, when inhaled into the lung, provides a time to reach peak plasma concentration (Tmax) of the active ingredient or its salt. The time to reach peak plasma concentration (Tmax) of the active ingredient or its salt may range from about 1 minute to about 1 hour. In some embodiments, the time to reach peak plasma concentration (Tmax) of the active ingredient or its salt may range from about 1 minute to about 10 minutes.

[0195] In some aspects, administration may be by oral ingestion, topical application, or inhalation. In some aspects, administration may include oral ingestion, which may include oral ingestion of food, liquid, gel, capsule, or any combination thereof. In some aspects, administration may include topical application, which may include topical application of lotion, tincture, balm, cream, oil, gel, butter, liquid, spray, ointment, paste, jelly, or any combination thereof. In some aspects, administration may include inhalation, which may include inhalation through a diffuser, inhaler, inhalation through a nebulizer, or any combination thereof. In some aspects, administration may include inhalation, which may include inhalation through a diffuser or inhaler. In some aspects, administration may include inhalation, which may include inhalation through a nebulizer. In some embodiments, administration can be performed at least about once a day, twice a day, three times a day, four times a day, five times a day, six times a day, or more than six times a day. In some cases, administration can be performed daily, once a week, once a month, or as needed. In some embodiments, administration can be performed once a day, twice a day, three times a day, or four times a day. In some cases, administration can be provided by the subject (e.g., patient), a health care provider, or both.

[0196] In some embodiments, administration can be carried out for about 1 day to about 8 days, 1 week to about 5 weeks, 1 month to about 12 months, 1 year to about 3 years, 3 years to about 10 years, 10 years to about 50 years, 25 years to about 100 years, or 50 years to about 130 years. In some embodiments, the composition can be administered as needed or for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, or chronically. Compositions for treating diseases

[0197] Also disclosed herein are methods for treating or preventing diseases, comprising administering a therapeutically effective amount of a powdered pharmaceutical composition to treat or prevent the disease or condition. For example, disclosed herein are methods for treating or preventing diseases, comprising administering a therapeutically effective amount of a powdered pharmaceutical composition by inhalation to treat or prevent the disease or condition. In certain cases, the powdered pharmaceutical formulation may include a glucagon-like peptide 1 receptor agonist (GLP-1), GLP-1-RA, a gastric inhibitory peptide receptor agonist, an incretin, liraglutide, glargine, glimepiride, semaglutide, sitagliptin, insulin, a pharmaceutically acceptable salt thereof, a derivative thereof, or a combination thereof. In certain cases, the powdered pharmaceutical formulation may have a human growth hormone receptor agonist, including a human growth hormone peptide, a salt, a derivative, or a combination thereof. The agonist can be used alone or as a pharmaceutical formulation to treat a condition. In some cases, the treatment or prevention may be for a deficiency of human growth hormone. In certain cases, the pharmaceutical formulation may include a steroid hormone receptor agonist or a pharmaceutically acceptable salt thereof and may be used to treat a disease or condition. In certain cases, the steroid hormone receptor agonist or a pharmaceutically acceptable salt thereof may be estrogen, testosterone, progesterone, or any combination thereof.

[0198] The pharmaceutical preparation can be used for the treatment or prevention of diabetes, such as type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), prediabetes, gestational diabetes, obesity, or a combination thereof.In some cases, the composition herein can be used to treat overweight, coronary artery disease (CAD), coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or any combination thereof.In some cases, the preparation herein can be used for alcohol use disorder, opioid use disorder, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cardiovascular disease, or any combination thereof.

[0199] In some embodiments, the powdered pharmaceutical formulation herein can be used to treat dementia.In some cases, dementia can include Alzheimer's disease, vascular dementia, Lewy body disease, frontotemporal dementia, alcohol-related dementia, early-onset dementia, mild cognitive impairment, or any combination thereof.In some embodiments, the powdered pharmaceutical formulation herein can be used to treat Parkinson's disease.In some embodiments, the powdered pharmaceutical formulation herein can be used for emotional well-being and / or mood.

[0200] In certain instances, the compositions herein, such as human growth hormone receptor agonists, can be used to increase calcium retention, promote muscle mass growth, promote lipolysis, promote visceral growth, reduce hepatic glucose uptake, promote hepatic gluconeogenesis, promote the maintenance and function of pancreatic islets, stimulate the immune system, improve cognitive function, treat Turner syndrome, treat chronic renal failure, treat Prader-Willi syndrome, treat intrauterine growth retardation, treat severe idiopathic short stature, maintain muscle mass against muscle wasting in subjects with AIDS, promote anti-aging, increase lean body mass, promote the maintenance or increase of body density, treat multiple sclerosis, promote weight loss, treat fibromyalgia, treat heart failure, treat Crohn's disease, treat ulcerative colitis, treat burns, or any combination thereof. In some instances, with regard to obesity, an individual may be defined as overweight if their body mass index (BMI) is between 25.0 and less than 30. In some cases, an individual may have stage 1 obesity if their BMI is less than 30-35. In some cases, an individual may have stage 2 obesity if their BMI is less than 30-40. In some cases, an individual may have stage 3 obesity, which is considered severe obesity when their BMI is 40 or above.

[0201] In certain cases, pharmaceutical preparations such as steroid hormone receptor agonist or its pharmaceutically acceptable salt can be used to treat conditions characterized by low testosterone level, such as depression, mood swings, irritability, obesity, fatigue, osteoporosis, osteopenia, muscle atrophy, sarcopenia, sleep apnea, hypogonadism, erectile dysfunction, low libido, underdevelopment of muscle mass, underdevelopment of secondary sexual characteristics, underdevelopment of body hair, underdevelopment of voice change, underdevelopment of tendons, underdevelopment of ligaments, underdevelopment of spermatogenesis, or any combination thereof.In some cases, depression can include major depression, melancholia, psychotic depression, prenatal depression, postpartum depression, dysthymic disorder, bipolar disorder, cyclothymic disorder, seasonal affective disorder, or any combination thereof.In some cases, the treatment herein can be used to treat low testosterone level, low estrogen level, and / or low progesterone level. In certain cases, the pharmaceutical preparations herein can be used to treat conditions characterized by low estrogen levels, such as menopause (for example, menopausal symptoms), regulation of female reproductive system, lack of female secondary sexual characteristics, decreased vaginal secretions, uterine hypoplasia, unwanted bone resorption, insufficient bone formation, undesirably low levels of body fat, thinning of vaginal wall, infertility, ovulation regulation, menstrual regulation, endometriosis, depression, obsessive-compulsive disorder, eating disorders, low libido that can be seen in both men and women, or any combination thereof.In some cases, menopausal symptoms can include hot flashes, flushing, night sweats, memory loss, breast tenderness, vasomotor symptoms, irritability, mood disorders, sleep disorders, fatigue, decreased libido, dyspareunia, atrophic vaginitis, or any combination thereof.

[0202] In certain cases, the pharmaceutical preparations herein can be used to treat conditions characterized by low progesterone levels, such as uterine cancer, cervical cancer, inability to prevent pregnancy, inability to maintain pregnancy, undesired premature birth, unwanted lactation during pregnancy, insufficient breast development for breastfeeding, skin aging, libido regulation, menopausal symptoms, or any combination thereof.In some cases, the pharmaceutical compositions herein can be used to treat thyroid disorders, osteoporosis, weight gain, or any combination thereof.In some cases, thyroid disorders can include hyperthyroidism, hypothyroidism, Hashimoto's thyroiditis, thyroid cancer, female thyroid disorders, postpartum thyroiditis, or any combination thereof.

[0203] In some embodiments, the subject may be a human, male, female, an individual over 18 years of age, an individual under 18 years of age, or any combination thereof. In some embodiments, the subject may be from about 1 day old to about 10 months old, from about 9 months old to about 24 months old, from about 1 year old to about 8 years old, from about 5 years old to about 25 years old, from about 20 years old to about 50 years old, from about 40 years old to about 80 years old, or from about 50 years old to about 130 years old.

[0204] In some embodiments, the powdered pharmaceutical formulations herein, such as metformin, can be used to treat type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), prediabetes, gestational diabetes, polycystic ovary syndrome, obesity, antipsychotic-induced weight gain, metabolic syndrome, liver disease, cardiovascular disease, kidney disease, and any combination thereof. In some embodiments, the powdered pharmaceutical formulations herein can be used to treat metabolic syndrome. In some cases, the powdered pharmaceutical composition can be used for life extension, healthspan extension, or both. In some cases, the powdered pharmaceutical composition can include at least partially encapsulated particles of metformin. In some cases, the at least partially encapsulated particles of metformin are added to a gummy candy.

[0205] In some aspects, the subject may have been diagnosed with the disease prior to treatment. In some aspects, the method may further include diagnosing the subject as having the disease. In some aspects, the diagnosing step may include using an in vitro diagnostic. In some aspects, the in vitro diagnostic may be a companion diagnostic.

[0206] In some embodiments, the diagnosis may include a physical examination, radiological imaging, blood tests, antibody tests, or any combination thereof. In some embodiments, the diagnosis may include radiological imaging, which may include computed tomography (CT) imaging, X-ray imaging, magnetic resonance imaging (MRI), ultrasound imaging, or any combination thereof.

[0207] In some embodiments, the method may further include administering a second treatment to the subject. In some cases, the composition may include the above-mentioned additional treatment. For example, the additional treatment may include a nonsteroidal anti-inflammatory drug, and the nonsteroidal anti-inflammatory drug may include aspirin, naproxen, ibuprofen, diclofenac, celecoxib, mefenamic acid, etoricoxib, indomethacin, any salt thereof, or any combination thereof. In some embodiments, the composition may include an excipient, a diluent, a carrier, or any combination thereof. In some embodiments, other non-opioid analgesics, such as acetaminophen, may be used. In other embodiments, opioid analgesics, such as hydrocodone, oxycodone, morphine, codeine, hydromorphone, oxymorphone, any salt thereof, or any combination thereof, may be used. In still other embodiments, the composition may include caffeine, theobromine, any salt thereof, or any combination thereof.

[0208] In some embodiments, administration of the composition is controlled by administering from about 500 μg (micrograms) to about 1000 mg, 10 μg to about 50 μg, 40 μg to about 90 μg, 80 μg to about 120 μg, 100 μg to about 150 μg, 140 μg to about 190 μg, 150 μg to about 220 μg, 200 μg to about 250 μg, 240 μg to about 300 μg, 290 μg to about 350 μg, 340 μg to about 410 μg, 400 μg to about 450 μg, 440 μg to about 500 μg, It can be made to range from 500 μg to about 700 μg, 600 μg to about 900 μg, 800 μg to about 1 mg, 1 mg to about 5 mg, 1 mg to about 10 mg, 5 mg to about 15 mg, 12 mg to about 25 mg, 20 mg to about 50 mg, 40 mg to about 80 mg, 70 mg to about 100 mg, 90 mg to about 150 mg, 125 mg to about 250 mg, 200 mg to about 500 mg, 400 mg to about 750 mg, 700 mg to about 900 mg, or about 850 mg to about 1000 mg. In some cases, the unit dose is greater than or equal to about 10 μg, greater than or equal to 25 μg, greater than or equal to 50 μg, greater than or equal to 75 μg, greater than or equal to 100 μg, greater than or equal to 150 μg, greater than or equal to 200 μg, greater than or equal to 220 μg, greater than or equal to 250 μg, or greater than or equal to 300 μg. greater than or equal to 350 μg, greater than or equal to 400 μg, greater than or equal to 400 μg, greater than or equal to 450 μg, greater than or equal to 500 μg, greater than or equal to 550 μg, greater than or equal to 600 μg, greater than or equal to 650 μg, greater than or equal to 700 μg, greater than or equal to 750 μg, greater than or equal to 800 μg,Greater than or equal to 850 μg, greater than or equal to 900 μg, greater than or equal to 900 μg, greater than or equal to 950 μg, greater than or equal to 1000 μg, greater than or equal to 2 mg, greater than or equal to 3 mg, greater than or equal to 4 mg, greater than or equal to 5 mg, greater than or equal to 6 mg, greater than or equal to 7 mg, greater than or equal to 8 mg, greater than or equal to 9 mg, greater than or equal to 10 mg, greater than or equal to 11 mg, greater than 12 mg or equal to 12 mg, greater than or equal to 13 mg, greater than or equal to 14 mg, greater than or equal to 15 mg, greater than or equal to 16 mg, greater than or equal to 17 mg, greater than or equal to 18 mg, greater than or equal to 19 mg, greater than or equal to 20 mg, greater than or equal to 21 mg, greater than or equal to 22 mg, greater than or equal to 23 mg, greater than or equal to 24 mg, or greater than or equal to 25 mg. In some cases, the unit dose is less than about 10 μg, less than 25 μg, less than 50 μg, less than 75 μg, less than 100 μg, less than 150 μg, less than 200 μg, less than 220 μg, less than 250 μg, less than 300 μg, less than 350 μg, less than 400 μg, less than 450 μg, less than 500 μg, less than 550 μg, less than 600 μg, less than 650 μg, less than 700 μg, less than 750 μg, less than 800 μg, or less than 850 μg. , less than 900μg, less than 950μg, less than 1000μg, less than 2mg, less than 3mg, less than 4mg, less than 5mg, less than 6mg, less than 7mg, less than 8mg, less than 9mg, less than 10mg, less than 11mg, less than 12mg, less than 13mg, less than 14mg, less than 15mg, less than 16mg, less than 17mg, less than 18mg, less than 19mg, less than 20mg, less than 21mg, less than 22mg, less than 23mg, less than 24mg,or less than 25 mg. In some cases, the hormone agonist or its salt may be administered in a unit dose of about 0.22 mg. In some cases, the hormone agonist or its salt may be administered in a unit dose of about 0.10 mg, 0.20 mg, 0.30 mg, 0.40 mg, or 0.50 mg.

[0209] Referring to Figure 1, Figure 1A shows a dry powder inhaler device for delivering a powdered pharmaceutical composition to the alveoli. The inhaler device may include a protective cap as shown in Figure 4, a rotatable upper portion with a mouthpiece as shown in Figure 5, a lower base chamber housing for receiving a pharmaceutical capsule as shown in Figure 6, a side button for mechanically puncturing the capsule with a sharp surface while inside the chamber as shown in Figure 7, and a chamber aerially connected to the mouthpiece to allow inhalation of the capsule contents. The dry powder inhaler device may include a base plate as shown in Figure 8. Figure 9 shows a dry powder inhaler device having a protective cap, a rotatable portion with a mouthpiece, a lower base chamber for puncturing the pill, and a base plate.

[0210] Referring to Figure 3, it shows a spray drying manufacturing system (either aqueous or solvent-based) that includes a closed spray drying vessel that receives a solution containing the drug dissolved or mixed in a suitable solvent. The solution then enters a particle formation chamber connected to an atomizer located at the top of the chamber. The atomizer is a two-component or rotary nozzle type that disperses the solution into fine droplets, controlled by atomizer pressure. The atomizing gas is an inert gas, either air or nitrogen. The atomized droplets pass through a hot gas drying chamber to produce uniform fine particles that maintain a small, coherent particle size distribution after evaporation of the liquid. Solid particles form and fall to the bottom of the drying chamber. The drying process is controlled by a balance between temperature, flow rate, and droplet size. The powder is collected from the exhaust gas using a cyclone or bag filter. Particle size is verified using a Malvern particle analyzer before blending with the excipient carrier. The active powder is blended with the excipient carrier (lactose) product in a Patterson Kelly (PK Blender), and the blended powder is fed into a hopper. From the hopper, the dry powder is placed into size 3 hypromellose capsules by a Bosch Encapsulator machine.

[0211] In some embodiments, the present disclosure provides a method for spray-drying liquid.In some cases, the liquid can comprise: i) hormone agonist or its pharmaceutically acceptable salt; ii) coating material, and the coating material can comprise trehalose, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS), cyclodextrin, maltodextrin, povidone, copovidone or any combination thereof; and iii) solvent, wherein the particles of hormone agonist or its pharmaceutically acceptable salt can be dispersed in liquid.In some cases, the particles of hormone agonist or its pharmaceutically acceptable salt dispersed in liquid can have a particle size ranging from about 1 micrometer to about 5 micrometers. In some cases, spray drying may include the steps of: i) atomizing droplets comprising the hormone agonist or a pharmaceutically acceptable salt thereof, a coating material, and a solvent; ii) drying the droplets to form substantially encapsulated particles, which may comprise the hormone agonist or a pharmaceutically acceptable salt thereof substantially encapsulated by the coating material; and iii) recovering the substantially encapsulated particles. Numbered Embodiments

[0212] Several compositions, kits, and methods are disclosed herein. Specific exemplary embodiments of these compositions, kits, and methods are disclosed below. The following embodiments describe non-limiting permutations of the combinations of features disclosed herein. Other permutations of the combinations of features are also contemplated. In particular, each of these numbered embodiments is intended to be dependent on or related to all preceding or following numbered embodiments, regardless of the order in which they are described.

[0213] Embodiment 1. A powdered pharmaceutical composition comprising: a) particles of a pharmaceutically acceptable excipient; and b) a plurality of spray-dried particles, each particle of the plurality of spray-dried particles being substantially encapsulated with a coating material, wherein the plurality of spray-dried particles substantially encapsulated with the coating material comprises an agonist selected from the group consisting of a steroid or a pharmaceutically acceptable salt thereof, a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof, and wherein among the plurality of spray-dried particles substantially encapsulated with the coating material, the coating 1. A powdered pharmaceutical composition, wherein at least a portion of the spray-dried particles substantially encapsulated with a coating material individually have a particle size ranging from about 1 micrometer to about 10 micrometers as measured by a particle analyzer using laser diffraction, and the coating material comprises trehalose, hydroxypropyl methylcellulose (HPMC), fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropyl methylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, phospholipids, or any combination thereof.

[0214] Embodiment 2. The powdered composition of embodiment 1, further comprising a cannabinoid, or a pharmaceutically acceptable salt thereof, comprising tetrahydrocannabinol delta-8, tetrahydrocannabinol delta-9, tetrahydrocannabinol delta-10, tetrahydrocannabinol delta-11, tetrahydrocannabinol delta-13, tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), full-spectrum THC, broad-spectrum THC, or a pharmaceutically acceptable salt thereof.

[0215] Embodiment 3. The powdered pharmaceutical composition of embodiment 1 or 2, wherein the spray-dried particles comprise a steroid agonist or a pharmaceutically acceptable salt thereof.

[0216] Embodiment 4. The powdered pharmaceutical composition of embodiment 3, wherein the steroid agonist is testosterone or a pharmaceutically acceptable salt thereof.

[0217] Embodiment 5. The powdered pharmaceutical composition of embodiment 3, wherein the steroid agonist is estrogen or a pharmaceutically acceptable salt thereof.

[0218] Embodiment 6 The powdered pharmaceutical composition of embodiment 3, wherein the steroid agonist is progesterone or a pharmaceutically acceptable salt thereof.

[0219] Embodiment 7. The powdered pharmaceutical composition of embodiment 1, wherein the spray-dried particles comprise a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof.

[0220] Embodiment 8. The powdered pharmaceutical composition of embodiment 1, wherein the spray-dried particles comprise a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof, and optionally the glucagon-like peptide 1 receptor agonist comprises semaglutide, liraglutide, or a pharmaceutically acceptable salt thereof.

[0221] Embodiment 9. The powdered pharmaceutical composition of any one of Embodiments 1 to 8, for use by inhalation or for nasal use.

[0222] Embodiment 10. The powdered pharmaceutical composition of any one of Embodiments 1 to 9, in unit dose form.

[0223] Embodiment 11. The powdered pharmaceutical composition of any one of embodiments 1-10, wherein at least a portion of the particles of the pharmaceutically acceptable excipient individually have a particle size ranging from about 1 micrometer to about 200 micrometers, or from about 1 micrometer to about 10 micrometers, as measured by a particle analyzer using laser diffraction.

[0224] Embodiment 12. The powdered pharmaceutical composition of any one of embodiments 1 to 11, wherein the particles are blended to form a substantially homogeneous mixture.

[0225] Embodiment 13. The powdered pharmaceutical composition of any one of Embodiments 1 to 12, contained in a capsule.

[0226] Embodiment 14. The powdered pharmaceutical composition of embodiment 13, wherein the capsule is filled with the powdered pharmaceutical composition to a volume that is about one-quarter to about one-half of the capsule's volume.

[0227] Embodiment 15. The powdered pharmaceutical composition of any one of embodiments 1 to 14, wherein the weight ratio of a) particles of a pharmaceutically acceptable excipient substantially encapsulated in the coating material to b) particles comprising the agonist or a pharmaceutically acceptable salt thereof ranges from about 1:1 (w / w) to about 10,000:1 (w / w).

[0228] Embodiment 16. The powdered pharmaceutical composition of embodiment 15, wherein the weight ratio of a) particles of pharmaceutically acceptable excipient to b) particles of agonist or a pharmaceutically acceptable salt thereof ranges from about 1:1 (w / w) to about 10:1 (w / w).

[0229] Embodiment 17. The powdered pharmaceutical composition of any one of embodiments 13 to 16, wherein the portion of the capsule not containing the powdered pharmaceutical composition contains a gas that at least partially comprises an inert gas.

[0230] Embodiment 18. The powdered pharmaceutical composition of embodiment 17, wherein the inert gas comprises nitrogen, carbon dioxide, helium, or any combination thereof.

[0231] Embodiment 19. The powdered pharmaceutical composition of embodiment 17 or 18, wherein the inert gas constitutes at least about 80%, 85%, 90%, or 95% of the gas by volume.

[0232] Embodiment 20. The powdered pharmaceutical composition of any one of embodiments 17-19, wherein the powdered pharmaceutical composition in the capsule, the gas in the capsule, or any combination thereof, contains less than about 10% water by weight, based on the weight of the powdered pharmaceutical composition or the total content of all gases in the capsule.

[0233] Embodiment 21. The powdered pharmaceutical composition of any one of embodiments 13 to 20, wherein the capsule comprises a hydroxypropyl methylcellulose (HPMC) capsule.

[0234] Embodiment 22. The powdered pharmaceutical composition of any one of embodiments 13 to 21, wherein the capsule is size 000, 00, 0, 1, 2, 3, or 4.

[0235] Embodiment 23. The powdered pharmaceutical composition of embodiment 22, comprising a capsule, wherein the capsule is size 3.

[0236] Embodiment 24. The powdered pharmaceutical composition of any one of Embodiments 1 to 23, contained in an inhaler unit.

[0237] Embodiment 25. The powdered pharmaceutical composition of any one of embodiments 13 to 24, wherein the capsule is contained in an inhaler unit.

[0238] Embodiment 26. The powdered pharmaceutical composition of any one of embodiments 1-25, wherein the pharmaceutically acceptable excipient comprises a carbohydrate, alginate, povidone, carbomer, flavoring, natural gum, silicone, alcohol, butter, wax, fatty acid, preservative, fumaryl diketopiperazine (FDKP), a pharmaceutically acceptable salt of any of these, or any combination thereof.

[0239] Embodiment 27. The powdered pharmaceutical composition of embodiment 26, wherein the pharmaceutically acceptable excipient or a pharmaceutically acceptable salt thereof comprises a carbohydrate or a pharmaceutically acceptable salt thereof, and the carbohydrate or a pharmaceutically acceptable salt thereof comprises lactose, microcrystalline cellulose, cellulose, mannitol, sorbitol, starch, starch glycolate, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, cyclodextrin, maltodextrin, croscarmellose sodium, corn starch, carrageenan, sorbitol, maltitol, glucose, a pharmaceutically acceptable salt of any of these, or any combination thereof.

[0240] Embodiment 28. The powdered pharmaceutical composition of embodiment 27, wherein the pharmaceutically acceptable excipient or a pharmaceutically acceptable salt thereof comprises lactose or a pharmaceutically acceptable salt thereof.

[0241] Embodiment 29. The powdered pharmaceutical composition of embodiment 28, comprising lactose or a pharmaceutically acceptable salt thereof, wherein the lactose or a pharmaceutically acceptable salt thereof comprises milled lactose, sieved lactose, micronized lactose, spray-dried lactose, at least substantially anhydrous lactose, lactose monohydrate, a pharmaceutically acceptable salt thereof, or any combination thereof.

[0242] Embodiment 30. The powdered pharmaceutical composition of any one of embodiments 1-29, wherein the powdered pharmaceutical composition described herein retains at least about 90% of its agonist after 6 months when stored in a sealed container at 25° C. and room air at a relative humidity of about 50 percent, as measured by HPLC.

[0243] Embodiment 31. The powdered pharmaceutical composition of any one of embodiments 1 to 30, wherein the agonist is present in an amount ranging from about 0.001 mg to about 20 mg.

[0244] Embodiment 32. The powdered pharmaceutical composition of any one of embodiments 1 to 31, wherein the agonist is in the form of a pharmaceutically acceptable salt thereof, which is hydrochloride, bitartrate, or borate.

[0245] Embodiment 33. The powdered pharmaceutical composition of any one of embodiments 1 to 32, wherein the agonist-containing particles have a median diameter of less than 5 μm.

[0246] Embodiment 34. The powdered pharmaceutical composition of any one of embodiments 1 to 33, wherein the particles comprising the agonist or a pharmaceutically acceptable salt thereof comprise a median diameter of less than about 6 μm, less than 7 μm, less than 8 μm, less than 9 μm, or less than 10 μm.

[0247] Embodiment 35. A kit comprising the powdered pharmaceutical composition of any one of Embodiments 1 to 34, at least partially contained in an encapsulating material.

[0248] Embodiment 36. A method of treating or preventing a disease or condition in a subject in need thereof, comprising administering to a subject in need thereof by inhalation a therapeutically effective amount of a first therapeutic agent comprising the powdered pharmaceutical composition of any one of Embodiments 1 to 34, thereby treating or preventing the disease or condition.

[0249] Embodiment 37. The method of embodiment 36, wherein administration is once daily, twice daily, three times daily, or four times daily.

[0250] Embodiment 38 The method of embodiment 36 or 37, wherein the agonist is a steroid agonist.

[0251] Embodiment 39 The method of embodiment 38, wherein the steroid agonist is testosterone.

[0252] Embodiment 40. The method of embodiment 39, wherein the disease or condition is selected from the group consisting of obesity, low libido, underdevelopment of muscle mass, failure to develop secondary sexual characteristics, depression, underdevelopment of body hair, failure to progress through voice change, underdevelopment of tendons and ligaments, and spermatogenesis failure.

[0253] Embodiment 41 The method of embodiment 38, wherein the steroid agonist is an estrogen.

[0254] Embodiment 42. The method of embodiment 41, further comprising a cannabinoid or a pharmaceutically acceptable salt thereof, including tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and cannabidiolic acid (CBDA), cannabielsoin (CBE), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone, cannabifuran, cannabiglendol, cannabilipsol, cannabicitran, or any combination thereof.

[0255] Embodiment 43. The method of embodiment 41 or 42, wherein the disease or condition is selected from the group consisting of absence of female secondary sexual characteristics, decreased vaginal fluids, uterine hypoplasia, unwanted bone resorption, insufficient bone formation, undesirably low levels of body fat, thinning of the vaginal wall, infertility, ovulation regulation, menstrual regulation, endometriosis, depression, obsessive-compulsive disorder, and eating disorders.

[0256] Embodiment 44 The method of embodiment 38, wherein the steroid agonist is progesterone.

[0257] Embodiment 45. The method of embodiment 44, further comprising a cannabinoid or a pharmaceutically acceptable salt thereof, including tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and cannabidiolic acid (CBDA), cannabielsoin (CBE), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone, cannabifuran, cannabiglendol, cannabilipsol, cannabicitran, or any combination thereof.

[0258] Embodiment 46. The method of embodiment 44 or 45, wherein the disease or condition is selected from the list consisting of uterine cancer, cervical cancer, failure to prevent pregnancy, failure to maintain pregnancy, unwanted premature birth, unwanted lactation during pregnancy, inadequate breast development for breastfeeding, skin aging, and libido regulation.

[0259] Embodiment 47 The method of embodiment 36 or 37, wherein the agonist is human growth hormone.

[0260] Embodiment 48. The method of embodiment 47, wherein the disease or condition is selected from the group consisting of inadequate calcium retention, low muscle mass, obesity, inadequate visceral growth, high hepatic glucose uptake, inadequate hepatic gluconeogenesis, pancreatic islet dysfunction, inadequate immune system stimulation, poor cognitive function, Turner syndrome, chronic renal failure, Prader-Willi syndrome, intrauterine growth retardation, severe idiopathic short stature, AIDS-related muscle mass wasting, low body density, multiple sclerosis, obesity, fibromyalgia, heart failure, Crohn's disease, and ulcerative colitis.

[0261] Embodiment 49 The method of embodiment 36 or 37, wherein the agonist is a GLP-1 receptor agonist.

[0262] Embodiment 50. The method of embodiment 49, wherein the disease or condition is selected from the list of type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), obesity, or a combination thereof, obesity, overweight, coronary artery disease (CAD), also known as coronary heart disease (CHD), ischemic heart disease (IHD), and myocardial ischemia.

[0263] Embodiment 51. The method of any one of embodiments 36-37, wherein the powdered pharmaceutical composition is administered as needed or for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, or chronically.

[0264] Embodiment 52 The method of any one of embodiments 36-51, wherein a second therapeutic agent, or a pharmaceutically acceptable salt thereof, is administered.

[0265] Embodiment 53 The method of embodiment 52, wherein a second therapeutic agent, or a pharmaceutically acceptable salt thereof, is administered simultaneously or sequentially.

[0266] Embodiment 54. The method of embodiment 52 or 53, wherein the second therapeutic agent, or a pharmaceutically acceptable salt thereof, is contained in a powdered pharmaceutical formulation.

[0267] Embodiment 55 The method of embodiment 52, wherein the first therapeutic agent comprises a steroid receptor agonist and the second therapeutic agent comprises a human growth hormone receptor agonist.

[0268] Embodiment 56. The method of any one of embodiments 36-55, wherein the subject has been diagnosed with a disease or condition.

[0269] Embodiment 57. The method of embodiment 56, wherein the diagnosis comprises the use of an in vitro diagnostic agent.

[0270] Embodiment 58 The method of embodiment 57, wherein the in vitro diagnostic is a companion diagnostic.

[0271] Embodiment 59. The method of any one of embodiments 36 to 58, wherein the powdered pharmaceutical composition is contained in a capsule, at least a portion of the capsule is contained within an inhaler, the inhaler contains a sharp surface configured to puncture or slice the capsule, and prior to administration, the inhaler is operated such that the capsule is punctured or sliced ​​by the sharp surface.

[0272] Embodiment 60. The method of any one of embodiments 36-59, wherein the inhalation is oral inhalation, intranasal administration, or any combination thereof.

[0273] Embodiment 61. A method for making a powdered pharmaceutical composition, comprising contacting in solution: a) an agonist, comprising an agonist selected from the group consisting of a steroid or a pharmaceutically acceptable salt thereof, a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof; b) a coating material, comprising trehalose, fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, a phospholipid, or any combination thereof; and c) a solvent; wherein the solution is spray-dried to form substantially encapsulated particles.

[0274] Embodiment 62. The powdered pharmaceutical composition of embodiment 61, wherein the spray drying comprises the steps of: a) atomizing droplets comprising the agonist or a pharmaceutically acceptable salt thereof, a coating material, and a solvent; b) drying the droplets to form substantially encapsulated particles, wherein the substantially encapsulated particles comprise the agonist or a pharmaceutically acceptable salt thereof substantially encapsulated by the coating material; and b) recovering the substantially encapsulated particles.

[0275] Embodiment 63. A method of treating or preventing a disease or condition in a subject in need thereof, comprising administering to a subject in need thereof by inhalation a therapeutically effective amount of a first therapeutic agent comprising the powdered pharmaceutical composition of embodiment 1, thereby treating or preventing the disease or condition.

[0276] Embodiment 64. The method of embodiment 63, wherein administration is once daily, twice daily, three times daily, or four times daily.

[0277] Embodiment 65. The method of embodiment 63 or 64, wherein the disease or condition is selected from the group consisting of obesity, low muscle mass, or infertility.

[0278] Embodiment 66. A powdered pharmaceutical composition comprising particles of a pharmaceutically acceptable carrier and a plurality of spray-dried particles, wherein each particle of the plurality of spray-dried particles is substantially unencapsulated, and wherein the substantially unencapsulated plurality of spray-dried particles comprises an agonist selected from the group consisting of a steroid or a pharmaceutically acceptable salt thereof, a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof, and wherein, among the plurality of spray-dried particles, when aerosolized, they comprise a mass median aerodynamic diameter of less than 5 μm and a fine particle fraction of at least about 40%, and the pharmaceutically acceptable carrier comprises trehalose, hydroxypropyl methylcellulose (HPMC), fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropyl methylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, phospholipid, or any combination thereof.

[0279] Embodiment 67. The pharmaceutical composition of embodiment 66, comprising at least about 2% to about 20% of the agonist.

[0280] Embodiment 68. The pharmaceutical composition of embodiment 67, wherein the agonist is a steroid agonist or a pharmaceutically acceptable salt thereof.

[0281] Embodiment 69. The pharmaceutical composition of embodiment 67, wherein the steroid agonist is testosterone or a pharmaceutically acceptable salt thereof.

[0282] Embodiment 70 The pharmaceutical composition of embodiment 67, wherein the steroid agonist is estrogen or a pharmaceutically acceptable salt thereof.

[0283] Embodiment 71. The pharmaceutical composition of embodiment 67, wherein the steroid agonist is progesterone or a pharmaceutically acceptable salt thereof.

[0284] Embodiment 72 The pharmaceutical composition of embodiment 67, wherein the agonist comprises a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof.

[0285] Embodiment 73 The pharmaceutical composition of embodiment 67, wherein the agonist comprises a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof.

[0286] Embodiment 74 The pharmaceutical composition of embodiment 67, wherein the agonist comprises a glucagon-like peptide receptor agonist or a pharmaceutically acceptable salt thereof.

[0287] Embodiment 75. The pharmaceutical composition of any one of embodiments 66 to 74, which is encapsulated to a nominal fill weight of about 3 mg to about 30 mg.

[0288] Embodiment 76. The pharmaceutical composition of any one of embodiments 66-74, which is encapsulated to provide a nominal dose of at least about 0.25 mg.

[0289] Embodiment 77. The pharmaceutical composition of any one of embodiments 66 to 74, which is encapsulated to provide a delivered dose of at least about 0.075 mg.

[0290] Embodiment Section 2:

[0291] Embodiment 1. A powdered composition comprising a plurality of spray-dried particles, wherein each particle of the plurality of spray-dried particles is at least partially encapsulated by a coating, and wherein the plurality of at least partially encapsulated spray-dried particles comprises metformin or a pharmaceutically acceptable salt thereof; Among the plurality of at least partially encapsulated spray-dried particles, a plurality of the at least partially encapsulated spray-dried particles individually have a particle size ranging from about 20 micrometers to about 200 micrometers as measured by a particle analyzer using laser diffraction; 1. A powdered composition, wherein the coating comprises hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cyclodextrin, maltodextrin, povidone, copovidone, methyl methacrylate (MMA), an enteric coating, or any combination thereof.

[0292] Embodiment 2. The powdered composition of embodiment 1, wherein the coating comprises methyl methacrylate (MMA).

[0293] Embodiment 3. The powdered composition of embodiment 1, wherein the coating comprises an enteric coating.

[0294] Embodiment 4. The powdered composition of embodiment 1, wherein metformin or a pharmaceutically acceptable salt thereof is present in an amount ranging from 100 mg to about 3000 mg, or from about 500 mg to about 2500 mg.

[0295] Embodiment 5. The powdered composition of embodiment 1 contained in a gummy candy.

[0296] Embodiment 6. The powdered composition of embodiment 5, wherein the gummies comprise gelatin, pectin, carrageenan, or any combination thereof.

[0297] Embodiment 7. A kit comprising the powdered composition of any one of embodiments 1 to 6 and a container.

[0298] Embodiment 8. A method of treating a disease or condition in a subject in need thereof, comprising orally administering to a subject in need thereof a therapeutically effective amount of the powdered composition of any one of Embodiments 1-6, thereby treating the disease or condition.

[0299] Embodiment 9. The method of embodiment 8, wherein the disease or condition is selected from the group consisting of type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), prediabetes, gestational diabetes, polycystic ovary syndrome, obesity, antipsychotic-induced weight gain, liver disease, cardiovascular disease, renal disease, and any combination thereof.

[0300] Embodiment 10. The method of embodiment 8 or 9, wherein administration is once daily, twice daily, three times daily, or four times daily.

[0301] Embodiment 11. The method of any one of embodiments 8-10, wherein the powdered pharmaceutical composition is administered as needed or for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, or chronically.

[0302] Embodiment 12 The method of any one of embodiments 8-11, wherein a second therapeutic agent or a pharmaceutically acceptable salt thereof is administered, optionally concurrently or sequentially. [Example]

[0303] The following examples are included for illustrative purposes only and are not intended to limit the scope of the disclosure. Example 1

[0304] The powdered pharmaceutical compositions described herein are administered via a dry powder inhaler or a nasal inhalation device. Referring to FIG. 1A, a dry powder inhalation device for delivering the powdered pharmaceutical compositions described herein to the alveoli is shown. The inhalation device includes a protective cap 101, a rotatable upper portion 102 with a mouthpiece, a lower base chamber housing 103 for receiving a pharmaceutical capsule, and a side button 104 for mechanically puncturing the capsule with a sharp surface while it is inside the chamber. The chamber is pneumatically connected to the mouthpiece, thereby enabling the capsule contents to be inhaled. FIG. 1B shows the nasal administration of a powdered pharmaceutical composition to a human subject via a nasal inhalation device. After puncturing a capsule containing the composition within the nasal inhalation device, the composition is inhaled through the nostrils. Example 2

[0305] A method of using an inhaler device to administer a dry powder pharmaceutical composition is shown in Figure 2. The process of administering a dry powder pharmaceutical composition includes seven steps. Step 1: Remove the inhaler from the case. Step 2: Remove the protective cap. Step 3: Hold the base of the inhaler and rotate the top in the direction of the arrow while holding the base of the unit. Step 4: Place the capsule inside the cavity of the lower base chamber. Step 5: Close the mouthpiece. Step 6: Press the buttons simultaneously to puncture the capsule. Step 7: Release the button. Hold the inhaler vertically, for example, do not tilt it more than about 30 degrees. The subject exhales twice and then places the tube into their mouth. The subject inhales quickly, holds their breath for about 2-3 seconds, and then exhales. Example 3

[0306] The active ingredient (e.g., hormone receptor agonist) in the dry powder pharmaceutical compositions described herein is produced by a spray drying system. Figure 3 shows a spray drying manufacturing system that includes a closed spray drying vessel that receives a solution containing the drug dissolved or mixed in a suitable solvent (aqueous or solvent-based). The solution then enters a particle formation chamber connected to an atomizer located at the top of the chamber. The atomizer is a two-component or rotary nozzle type that disperses the solution into fine droplets, controlled by atomizer pressure. The atomizing gas is an inert gas, such as air, nitrogen, or carbon dioxide. The atomized droplets are passed through a hot gas drying chamber to produce uniform fine particles that maintain a small, coherent particle size distribution after evaporation of the liquid. Solid particles are formed and fall to the bottom of the drying chamber. The drying process is controlled by a balance between temperature, flow rate, and droplet size. The powder is collected from the exhaust gas using a cyclone or bag filter. The particle size is verified using a Malvern particle analyzer before blending with the excipient carrier. The active powder is blended with the excipient carrier (lactose) product in a Patterson Kelly (PK Blender) and the blended powder is fed into a hopper from which the dry powder is placed into size 3 hypromellose capsules by a Bosch Encapsulator machine. Example 4

[0307] A male subject has insufficient muscle mass. The subject is administered a pharmaceutical composition once a week for six months in combination with an exercise regimen. The pharmaceutical composition comprises testosterone processed into a dry powder using a method described herein (e.g., spray drying). The dry powder is mixed with lactose powder and encapsulated. A hormone agonist is encapsulated in a capsule and administered intranasally using an inhaler. The dosing regimen comprises an effective amount of testosterone to increase muscle mass, in combination with an exercise regimen. The inhaled pharmaceutical composition is absorbed into the bloodstream at least five times faster than an equivalent pharmaceutical composition administered orally. Example 5

[0308] The powdered pharmaceutical compositions described herein are administered by a dry powder inhaler. Referring to Figure 9, a dry powder inhaler device for delivering the powdered pharmaceutical compositions described herein to the alveoli is shown. The inhaler device includes a protective cap 201, a rotatable top 202 with a mouthpiece, a lower base chamber receiving portion 206 for receiving a pharmaceutical capsule 203, and a side button 204 for mechanically puncturing the capsule with a sharp surface using a spring 205 while the capsule is inside the chamber. The chamber is pneumatically connected to the mouthpiece, thereby allowing the capsule contents to be inhaled. A bottom plate 207 fits into the lower base chamber receiving portion. Example 6

[0309] Testosterone in a dry powder pharmaceutical composition was produced using a spray-drying system. Figure 10 shows a spray-drying manufacturing system that includes a closed spray-drying chamber that receives a solution containing a polymer wall material (i.e., HPMCAS) and an active ingredient (i.e., testosterone) dissolved in a solvent (e.g., 70% ethanol and 30% water). The dissolved polymer wall material and testosterone were thoroughly mixed to form a liquid suspension. The liquid suspension was then fed into an atomizer located at the top of the chamber. The atomizer is a two-component or rotary nozzle type that disperses the solution into fine droplets, controlled by atomizer pressure. The atomizing gas is an inert gas, such as air, nitrogen, or carbon dioxide. The atomized droplets were then sent through a drying chamber with hot gas to produce uniform fine particles that maintained a small, coherent particle size distribution after evaporation of the liquid. Solid particles formed and fell to the bottom of the drying chamber as amorphous crystals. The drying process was controlled using a balance between temperature, flow rate, and droplet size. The powder was collected from the exhaust gas using a cyclone or bag filter. Before blending with the excipient carriers, the particle size was verified by a Malvern particle analyzer.

[0310] The active powder was blended with the excipient carrier (i.e., lactose) product in a Patterson Kelly (PK Blender), and the blended powder was fed into a hopper. From the hopper, a Bosch Encapsulator machine placed the dry powder into size 3 hypromellose capsules. A small amount of microencapsulated testosterone was blended into a V-blender using an intensifier bar operating at high speed to uniformly disperse the active powder throughout the excipient carrier. The V-blender could be a Patterson Kelly / PK Blender, a Gemco blender, or a Ross blender.

[0311] The blended powder was then loaded into the hopper of an encapsulator machine ("encapsulator"), which dispensed the powder into capsules. The encapsulator automatically separated the top ("cap") and body ("shell") of the capsule, slugging the powder and then transferring it to the capsule body. The capsule halves were then closed together to form a sealed capsule containing the blended powder. During filling, the atmosphere inside the capsule was inert with nitrogen to prevent oxidation and remove moisture from the blend, thus allowing the powder to flow freely from the capsule and be inhalable using a dry powder inhaler. The dry powder was placed into hypromellose capsules by a Bosch, ACG, or IMA Encapsulator machine. Example 7

[0312] A male subject has low libido. A pharmaceutical composition is administered to the subject to treat low libido. The pharmaceutical composition comprises an encapsulated hormone agonist (e.g., testosterone) that is processed into a dry powder using a method described herein (e.g., spray drying). The dry powder is mixed with lactose powder and encapsulated. The hormone agonist is encapsulated and administered intranasally using an inhaler. The dosage regimen comprises an effective amount of the hormone agonist to treat low libido. Example 8

[0313] A male subject has been diagnosed with obesity. The subject is administered a pharmaceutical composition to treat obesity. The pharmaceutical composition comprises encapsulated liraglutide processed into a dry powder using a method described herein (e.g., spray drying). The dry powder is mixed with lactose powder and encapsulated. The liraglutide is encapsulated in a capsule and administered using a dry powder inhaler. The dosing regimen comprises an effective amount of liraglutide to induce weight loss, as measured by measuring the subject's weight at the start of the treatment regimen and comparing it with the subject's weight after the treatment regimen. Administration is continued daily or weekly until the desired weight loss is achieved. Example 9

[0314] Crystallized testosterone containing approximately 99% testosterone is used to prepare testosterone inhalation powder by spray drying. Testosterone (3.9 g) is dissolved in approximately 290 ml of 200-proof ethanol. A separate solution of 1,2-distearoyl-sn-glycero-3-phosphocholine (1.5 g) is prepared in approximately 50 ml of 200-proof ethanol and then added to the testosterone solution. FDKP (9.6 g), approximately 50 ml of ethanol, and 98 ml of water are added to the testosterone mixture. The resulting suspension is spray-dried in a system equipped with an inert loop, dehumidifier, and condenser. The spray dryer is operated at a feed rate of 10%, a suction rate of 90%, a nitrogen flow rate of 60 mm, and an inlet temperature of 150°C. The resulting powder is analyzed by high-performance liquid chromatography to determine the percent drug content. Example 10

[0315] A subject has been diagnosed with type 2 diabetes. The subject is administered a pharmaceutical composition to treat type 2 diabetes. The pharmaceutical composition comprises microencapsulated metformin processed into an encapsulated dry powder using a method described herein (e.g., spray drying). Metformin particles are microencapsulated with an enteric coating, e.g., methyl methacrylate (MMA). The microencapsulated metformin powder is mixed with gelatin and other ingredients to form a gummy. The metformin gummy is administered to the subject. The dosing regimen comprises an effective amount of metformin to treat type 2 diabetes. Administration continues daily to treat type 2 diabetes. Example 11

[0316] Seven male subjects were administered microencapsulated testosterone to replace testosterone injections. The pharmaceutical composition contained HPMCAS-microencapsulated testosterone processed into a dry powder using the methods described herein. The dry powder was mixed with excipients. The encapsulated testosterone and excipients were placed in capsules and administered orally via an inhaler. Four of the seven subjects demonstrated substantial increases in testosterone levels when tested in an in vitro assay to measure testosterone levels. Example 12

[0317] A subject was administered microencapsulated liraglutide for appetite suppression. The pharmaceutical composition contained HPMCAS-microencapsulated liraglutide processed into a dry powder using the methods described herein. The dry powder was mixed with excipients. The encapsulated liraglutide and excipients were placed in a capsule and administered orally via an inhaler. The subject experienced no adverse effects from the administration of liraglutide.

[0318] While preferred embodiments of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are presented by way of example only. Numerous variations, changes, and substitutions will readily occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein can be used to practice the methods shown in the present disclosure. It is intended that the following claims define the scope of the disclosure, and that methods and structures that fall within the scope of these claims and their equivalents be covered thereby.

Claims

1. a) particles of a pharmaceutically acceptable excipient; b) a plurality of spray-dried particles; A powdered pharmaceutical composition comprising: each particle of the plurality of spray-dried particles substantially encapsulated with a coating material, and the plurality of spray-dried particles substantially encapsulated with the coating material are comprising an agonist selected from the group consisting of a steroid or a pharmaceutically acceptable salt thereof, a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof; among the plurality of spray-dried particles substantially encapsulated with the coating material, at least a portion of the spray-dried particles substantially encapsulated with the coating material individually have a particle size ranging from about 1 micrometer to about 10 micrometers as measured by a particle analyzer using laser diffraction; the coating material comprises trehalose, hydroxypropyl methylcellulose (HPMC), fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropyl methylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, phospholipids, or any combination thereof; A powdered pharmaceutical composition.

2. 10. The powdered pharmaceutical composition of claim 1, further comprising a cannabinoid or a pharmaceutically acceptable salt thereof, including tetrahydrocannabinol delta-8, tetrahydrocannabinol delta-9, tetrahydrocannabinol delta-10, tetrahydrocannabinol delta-11, tetrahydrocannabinol delta-13, tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), full-spectrum THC, broad-spectrum THC, or a pharmaceutically acceptable salt thereof.

3. 2. The powdered pharmaceutical composition of claim 1, wherein the spray-dried particles comprise the steroid or a pharmaceutically acceptable salt thereof.

4. 4. The powdered pharmaceutical composition of claim 3, wherein the steroid is testosterone or a pharmaceutically acceptable salt thereof.

5. 4. The powdered pharmaceutical composition according to claim 3, wherein the steroid is estrogen or a pharmaceutically acceptable salt thereof.

6. 4. The powdered pharmaceutical composition according to claim 3, wherein the steroid is progesterone or a pharmaceutically acceptable salt thereof.

7. 10. The powdered pharmaceutical composition of claim 1, wherein the spray-dried particles comprise the human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof.

8. 2. The powdered pharmaceutical composition of claim 1, wherein the spray-dried particles comprise the glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof, and the glucagon-like peptide 1 receptor agonist comprises semaglutide, liraglutide, or a pharmaceutically acceptable salt of either of these.

9. 10. The powdered pharmaceutical composition of claim 1, wherein the powdered pharmaceutical composition is for inhalation or nasal administration.

10. 10. The powdered pharmaceutical composition of claim 1, wherein the pharmaceutical composition is in unit dose form.

11. 10. The powdered pharmaceutical composition of claim 1, wherein at least a portion of the particles of the pharmaceutically acceptable excipient individually have a particle size ranging from about 1 micrometer to about 200 micrometers, from about 1 micrometer to about 10 micrometers, or from about 50 micrometers to about 200 micrometers as measured by a particle analyzer using laser diffraction.

12. 10. The powdered pharmaceutical composition of claim 1, wherein the particles are blended to form a substantially homogeneous mixture.

13. 10. The powdered pharmaceutical composition of claim 1, which is contained in a capsule.

14. 14. The powdered pharmaceutical composition of claim 13, wherein the capsule is filled with the powdered pharmaceutical composition to a volume that is about one-quarter to about one-half of the capsule's volume.

15. 2. The powdered pharmaceutical composition of claim 1, wherein the weight ratio of a) the particles of the pharmaceutically acceptable excipient substantially encapsulated with a coating material to b) the particles comprising the agonist or a pharmaceutically acceptable salt thereof ranges from about 1:1 (w / w) to about 10,000:1 (w / w).

16. 16. The powdered pharmaceutical composition of claim 15, wherein the weight ratio of a) the particles of the pharmaceutically acceptable excipient to b) the particles of the agonist or the pharmaceutically acceptable salt thereof ranges from about 1:1 (w / w) to about 10:1 (w / w).

17. 14. The powdered pharmaceutical composition of claim 13, wherein the portion of the capsule not containing the powdered pharmaceutical composition contains a gas that comprises at least in part an inert gas.

18. 14. The powdered pharmaceutical composition of claim 13, wherein the capsule comprises a hydroxypropyl methylcellulose (HPMC) capsule.

19. 14. The powdered pharmaceutical composition of claim 13, wherein the capsule is size 000, 00, 0, 1, 2, 3, or 4.

20. 20. The powdered pharmaceutical composition of claim 19, comprising a capsule, wherein the capsule is size 3.

21. 10. The powdered pharmaceutical composition of claim 1 contained in an inhaler unit.

22. 14. The powdered pharmaceutical composition of claim 13, wherein the capsule is contained in an inhaler unit.

23. 10. The powdered pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient comprises a carbohydrate, alginate, povidone, carbomer, flavoring, natural gum, silicone, alcohol, butter, wax, fatty acid, preservative, fumaryl diketopiperazine (FDKP), a pharmaceutically acceptable salt of any of these, or any combination thereof.

24. 24. The powdered pharmaceutical composition of claim 23, wherein the pharmaceutically acceptable excipient comprises the carbohydrate or the pharmaceutically acceptable salt thereof, and the carbohydrate or the pharmaceutically acceptable salt thereof comprises lactose, microcrystalline cellulose, cellulose, mannitol, sorbitol, starch, starch glycolate, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, cyclodextrin, maltodextrin, croscarmellose sodium, corn starch, carrageenan, sorbitol, maltitol, glucose, a pharmaceutically acceptable salt of any of these, or any combination thereof.

25. 10. The powdered pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient comprises lactose or a pharmaceutically acceptable salt thereof.

26. 26. The powdered pharmaceutical composition of claim 25, comprising lactose or the pharmaceutically acceptable salt thereof, wherein the lactose or the pharmaceutically acceptable salt thereof comprises milled lactose, sieved lactose, micronized lactose, spray-dried lactose, at least substantially anhydrous lactose, lactose monohydrate, a pharmaceutically acceptable salt thereof, or any combination thereof.

27. 10. The powdered pharmaceutical composition of claim 1, wherein the powdered pharmaceutical composition described herein retains at least about 90% of its agonist after 6 months when stored in a sealed container at 25°C and room air at a relative humidity of about 50 percent, as measured by HPLC.

28. 10. The powdered pharmaceutical composition of claim 1, wherein the agonist is present in an amount ranging from about 0.001 mg to about 20 mg.

29. 2. The powdered pharmaceutical composition of claim 1, wherein the agonist is in the form of a pharmaceutically acceptable salt thereof, which is a hydrochloride, bitartrate, or borate salt.

30. 10. The powdered pharmaceutical composition of claim 1, wherein the particles comprising the agonist comprise a median diameter of less than about 5 μm, less than 6 μm, less than 7 μm, less than 8 μm, less than 9 μm, or less than 10 μm.

31. A kit comprising the powdered pharmaceutical composition of claim 1, at least a portion of which is contained in a container.

32. A method for treating a disease or condition in a subject in need thereof, comprising administering to the subject in need thereof by inhalation a therapeutically effective amount of a first therapeutic agent comprising the powdered pharmaceutical composition of claim 1, thereby treating the disease or condition.

33. 33. The method of claim 32, wherein the administration occurs once daily, twice daily, three times daily, or four times daily.

34. 33. The method of claim 32, wherein the agonist is the steroid or a pharmaceutically acceptable salt thereof.

35. 35. The method of claim 34, wherein the steroid or the pharmaceutically acceptable salt thereof is testosterone or a salt thereof.

36. 33. The method of claim 32, wherein the disease or condition is selected from the group consisting of obesity, low libido, underdevelopment of muscle mass, failure to develop secondary sexual characteristics, depression, underdevelopment of body hair, failure to progress through voice change, underdevelopment of tendons, underdevelopment of ligaments, and spermatogenesis failure.

37. 35. The method of claim 34, wherein the steroid or the pharmaceutically acceptable salt thereof is an estrogen or a salt thereof.

38. 33. The method of claim 32, wherein the powdered pharmaceutical composition further comprises a cannabinoid or a pharmaceutically acceptable salt thereof, including tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and cannabidiolic acid (CBDA), cannabielsoin (CBE), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone, cannabifuran, cannabiglendol, cannabilipsol, cannabicitran, or any combination thereof.

39. 33. The method of claim 32, wherein the disease or condition is selected from the group consisting of absence of female secondary sexual characteristics, decreased vaginal fluids, uterine hypoplasia, unwanted bone resorption, insufficient bone formation, undesirably low levels of body fat, thinning of the vaginal wall, infertility, ovulation regulation, menstrual regulation, endometriosis, depression, obsessive-compulsive disorder, and eating disorders.

40. 35. The method of claim 34, wherein the steroid or the pharmaceutically acceptable salt thereof is progesterone or a salt thereof.

41. 33. The method of claim 32, wherein the disease or condition is selected from the list consisting of uterine cancer, cervical cancer, failure to prevent pregnancy, failure to maintain pregnancy, unwanted premature birth, unwanted lactation during pregnancy, inadequate breast development for breastfeeding, skin aging, and libido regulation.

42. 33. The method of claim 32, wherein the agonist is the human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof.

43. 33. The method of claim 32, wherein the disease or condition is selected from the group consisting of inadequate calcium retention, low muscle mass, obesity, inadequate visceral growth, high hepatic glucose uptake, inadequate hepatic gluconeogenesis, pancreatic islet dysfunction, inadequate immune system stimulation, poor cognitive function, Turner syndrome, chronic renal failure, Prader-Willi syndrome, intrauterine growth restriction, severe idiopathic short stature, AIDS-induced muscle mass wasting, low body density, multiple sclerosis, obesity, fibromyalgia, heart failure, Crohn's disease, and ulcerative colitis.

44. 33. The method of claim 32, wherein the agonist is the glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof.

45. 33. The method of claim 32, wherein the disease or condition is selected from the list of type 1 diabetes, type 2 diabetes, type 3c diabetes (pancreatic diabetes), obesity, overweight, coronary artery disease (CAD), dementia, coronary heart disease (CHD), ischemic heart disease (IHD), and myocardial ischemia.

46. 33. The method of claim 32, wherein the powdered pharmaceutical composition is administered as needed or for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, or chronically.

47. 33. The method of claim 32, wherein a second therapeutic agent or a pharmaceutically acceptable salt thereof is administered.

48. 48. The method of claim 47, wherein the second therapeutic agent or the pharmaceutically acceptable salt thereof is administered simultaneously or sequentially.

49. 48. The method of claim 47, wherein the second therapeutic agent or the pharmaceutically acceptable salt thereof is contained in a powdered pharmaceutical formulation.

50. 48. The method of claim 47, wherein the first therapeutic agent comprises the steroid or a pharmaceutically acceptable salt thereof, and the second therapeutic agent comprises the human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof.

51. 33. The method of claim 32, wherein the subject has been diagnosed with the disease or condition.

52. 52. The method of claim 51, wherein the diagnosis comprises the use of an in vitro diagnostic agent.

53. 53. The method of claim 52, wherein the in vitro diagnostic is a companion diagnostic.

54. 33. The method of claim 32, wherein the inhalation is oral inhalation, nasal administration, or any combination thereof.

55. particles of a pharmaceutically acceptable carrier; A plurality of spray-dried particles A powdered pharmaceutical composition comprising: each particle of the plurality of spray-dried particles is substantially unencapsulated, and the plurality of substantially unencapsulated spray-dried particles comprises: comprising an agonist selected from the group consisting of a steroid or a pharmaceutically acceptable salt thereof, a human growth hormone receptor agonist or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof; among the plurality of spray-dried particles, the spray-dried particles, when aerosolized, comprise a mass median aerodynamic diameter of less than 5 μm and a fine particle fraction of at least about 40%; The pharmaceutically acceptable carrier comprises trehalose, hydroxypropyl methylcellulose (HPMC), fumaryl diketopiperazine (FDKP), 1,2-distearoyl-sn-glycero-3-phosphocholine, hydroxypropyl methylcellulose acetate succinate (HPMCAS), povidone, copovidone, lactose, phospholipids, or any combination thereof; A powdered pharmaceutical composition.

56. 56. The powdered pharmaceutical composition of claim 55, wherein said powdered pharmaceutical composition comprises at least about 2% to about 20% of said agonist.

57. 56. The powdered pharmaceutical composition of claim 55, wherein the agonist is the steroid or a pharmaceutically acceptable salt thereof.

58. 58. The powdered pharmaceutical composition of claim 57, wherein the steroid or the pharmaceutically acceptable salt thereof is testosterone or a pharmaceutically acceptable salt thereof.

59. 58. The powdered pharmaceutical composition of claim 57, wherein the steroid or the pharmaceutically acceptable salt thereof is an estrogen or a pharmaceutically acceptable salt thereof.

60. 58. The powdered pharmaceutical composition of claim 57, wherein the steroid or the pharmaceutically acceptable salt thereof is progesterone or a pharmaceutically acceptable salt thereof.

61. 56. The powdered pharmaceutical composition of claim 55, wherein said agonist is said human growth hormone receptor agonist or said pharmaceutically acceptable salt thereof.

62. 56. The powdered pharmaceutical composition of claim 55, wherein the agonist is the glucagon-like peptide 1 receptor agonist or a pharmaceutically acceptable salt thereof.

63. 56. The powdered pharmaceutical composition of claim 55, wherein the powdered pharmaceutical composition comprises the agonist in an amount from about 3 mg to about 30 mg.

64. 56. The powdered pharmaceutical composition of claim 55, wherein said powdered pharmaceutical composition comprises said agonist in an amount of at least about 0.25 mg.

65. 56. The powdered pharmaceutical composition of claim 55, wherein the powdered pharmaceutical composition is encapsulated to have a delivered dose of at least about 0.075 mg.

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