Compositions with improved bioavailability of therapeutic agents

Abstract

The present specification discloses a pharmaceutical composition comprising one or more therapeutic compounds, one or more glycerolipids, and one or more digestive enhancers as disclosed herein. The disclosed glycerolipids include one or more hard fats and one or more liquid fats. The disclosed digestive enhancers include one or more bile acids, one or more phospholipids, one or more free C 14-24 Fatty acids, with at least one free C 14-24 A fatty acid surfactant, a fatty acid surfactant, or any combination thereof. Also disclosed herein are methods and procedures for formulating one or more of the disclosed therapeutic compounds into the disclosed pharmaceutical compositions.

Description

[Technical field]

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 269,330, filed March 14, 2022, and U.S. Provisional Patent Application No. 63 / 166,995, filed March 27, 2021, and is a 35 U.S.C. §111 application entitled to the filing date under 35 U.S.C. §119(e), the contents of which are incorporated herein by reference in their entireties. [Background technology]

[0002] Oral delivery of therapeutic compounds is the most preferred route of administration, accounting for 80% of all pharmaceutical compositions on the market. The premise underlying traditional oral delivery is that the therapeutic compound must first be released from the composition into the gastrointestinal fluids, absorbed by the capillaries lining the duodenum of the small intestine, and then distributed throughout the body by the bloodstream. However, the effectiveness of oral delivery typically depends on the pharmacokinetic properties of the pharmaceutical composition and the therapeutic compound formulated therein, with the amount of therapeutic compound released from the pharmaceutical composition (dissolution rate) and the amount of therapeutic compound absorbed into the systemic circulation and made available to the body (i.e., bioavailability) being two major critical factors.

[0003] Both poorly water-soluble or hydrophobic therapeutic compounds present particularly difficult oral delivery challenges due to their low aqueous solubility and slow dissolution rate in the aqueous gastrointestinal environment. To solve these problems, the pharmaceutical industry has traditionally focused on optimizing formulations of pharmaceutical compositions in ways that 1) improve the dissolution rate of the hydrophobic therapeutic compound in the formulation to increase the amount released to the gastrointestinal tract, and / or 2) improve the bioavailability of the hydrophobic therapeutic compound to increase the amount delivered systemically to the body.

[0004] For hydrophilic therapeutic compounds, the formulation challenges are different. Although these compounds are readily soluble in the aqueous gastrointestinal environment, many are poorly absorbed due to poor membrane permeability and / or enzymatic degradation. Many solid dosage formulations of hydrophilic therapeutic compounds exhibit poor or no absorption of the therapeutic compound.

[0005] One approach to improve the pharmacokinetics of pharmaceutical compositions containing hydrophobic therapeutic compounds has been to ingest the pharmaceutical composition with a high-fat-containing meal to promote absorption in the small intestine and thus increase its bioavailability. Ingestion of a meal triggers the gastric digestive process, including the release of bile from the gallbladder into the duodenum, which breaks down and absorbs fat from the food. Although such a meal does not generally affect the dissolution rate, the absorption of the released therapeutic compound enters the systemic circulation in greater amounts due to the concomitant absorption of dietary fat.

[0006] Another approach to improve the pharmacokinetics of pharmaceutical compositions containing hydrophobic therapeutic compounds has been the use of phospholipid-based formulations, including macroemulsions, microemulsions, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS), solid lipid nanoparticles (SLN), liposomes and lipoplexes. These surfactant-based formulations generate oil-based emulsions containing the therapeutic compounds that facilitate absorption by the small intestine into the systemic circulation, thus increasing the bioavailability of the therapeutic compounds. However, in addition to generally not affecting the dissolution rate, such surfactant-based formulations also destabilize the membrane lining of the stomach, causing irritation. Further limitations associated with this approach include, for example, in vivo drug precipitation, formulation processing issues, limited lymphatic uptake, lack of predictive in vitro testing, and oxidation of unsaturated fatty acids, which limit their potential use. Thus, the wide variability of the bioavailability of therapeutic compounds remains a challenging obstacle. Summary of the Invention [Problem to be solved by the invention]

[0007] The present specification provides an alternative approach in which the pharmaceutical compositions disclosed herein are formulated to rely on physiological lipid digestion and absorption systems to achieve absorption and enhanced efficacy, increasing the bioavailability of therapeutic compounds to better facilitate the treatment of diseases or disorders.Furthermore, such formulations are not only applicable to highly lipophilic therapeutic compounds, but also provide a means to increase the solubility of therapeutic compounds that are generally poorly soluble in both aqueous and lipid matrices. [Means for solving the problem]

[0008] Aspects of the present specification partially disclose pharmaceutical compositions comprising a) one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestive enhancers. The therapeutic compounds disclosed herein can be hydrophilic therapeutic compounds, hydrophobic therapeutic compounds, or pharmaceutical active agents or components, diagnostic agents or components, cosmetic active agents or components, or nutraceutical active agents or components. The glycerolipids disclosed herein include hard fats and liquid fats. Hard fats are glycerolipids that are solid at 18°C ​​and contain triglycerides. Liquid fats are glycerolipids that are liquid at 18°C ​​and also contain partially hydrolyzed glycerolipids and monoglycerides. The digestive enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C 14-24 The surfactants include fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives with polyhydroxylated head groups, one or more steroid surfactants, or any combination thereof. The compositions disclosed herein may further include one or more pharma- ceutically acceptable stabilizers.

[0009] Other aspects herein disclose a method of treating an individual having a disease or disorder, comprising administering a composition disclosed herein to an individual in need thereof, whereby symptoms associated with the disease or disorder are alleviated, thereby treating the individual. Other aspects herein disclose the use of a composition disclosed herein in the manufacture of a medicament for treating a disease or disorder. Other aspects herein disclose a composition disclosed herein for use in treating a disease or disorder.

[0010] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate aspects of the disclosed subject matter in at least one of its exemplary embodiments, as defined in more detail in the following description. Features, elements, and aspects of the disclosure are referenced by numerals having like numerals in different drawings that represent the same, equivalent, or similar features, elements, or aspects according to one or more embodiments. The drawings are not necessarily to scale, emphasis instead being placed on illustrating principles as described herein and provided by exemplary embodiments of the invention. [Brief description of the drawings]

[0011] [Figure 1A] 1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate, with FIG. 1A showing a representative PXRD spectrum of the GELCURE® 43 / 01 standard. [Figure 1B] 1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate, and FIG. 1B shows a representative PXRD spectrum of a cholic acid standard. [Figure 1C] 1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate, and FIG. 1C shows a representative PXRD spectrum of a fenofibrate standard. [Figure 1D]1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate, and FIG. 1D shows a representative PXRD spectrum of a vehicle standard. [Figure 1E] 1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions that include fenofibrate, and FIG. 1E shows a representative PXRD spectrum of the disclosed pharmaceutical compositions that include a fenofibrate standard. [Figure 1F] Figures 1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate, and Figure 1F shows a representative PXRD spectrum of a fenofibrate standard overlaid on a representative PXRD spectrum of a disclosed pharmaceutical composition containing a fenofibrate standard, with asterisks above the peaks to indicate overlap of the relevant peaks. [Figure 1G] Figures 1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate, and Figure 1G shows a representative PXRD spectrum of a cholic acid standard overlaid on a representative PXRD spectrum of a vehicle standard, with asterisks above the peaks to indicate overlap of the relevant peaks. [Figure 1H] Figures 1A-1H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate, and Figure 1H shows a representative PXRD spectrum of a cholic acid standard overlaid on the disclosed pharmaceutical compositions containing fenofibrate standard, with asterisks above the peaks indicating overlap of relevant peaks.

[0012] [Figure 2A] 2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, with FIG. 2A showing a representative PXRD spectrum of the GELCURE® 43 / 01 standard. [Figure 2B]2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, and FIG. 2B shows a representative PXRD spectrum of a cholic acid standard. [Figure 2C] 2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, and FIG. 2C shows a representative PXRD spectrum of an aprepitant standard. [Figure 2D] 2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, and FIG. 2D shows a representative PXRD spectrum of a vehicle standard. [Figure 2E] 2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, and FIG. 2E shows a representative PXRD spectrum of the disclosed pharmaceutical compositions containing an aprepitant standard. [Figure 2F] Figures 2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, and Figure 2F shows a representative PXRD spectrum of the aprepitant standard overlaid on a representative PXRD spectrum of the disclosed pharmaceutical compositions containing the aprepitant standard, with asterisks above the peaks indicating the overlap of the relevant peaks. [Figure 2G] 2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, and FIG. 2G shows a representative PXRD spectrum of cholic acid standards overlaid on a representative PXRD spectrum of vehicle standards. [Figure 2H] Figures 2A-2H show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing aprepitant, and Figure 2H shows a representative PXRD spectrum of cholic acid standards overlaid on the disclosed pharmaceutical compositions containing aprepitant standards.

[0013] [Figure 3A]Figures 3A-3B show representative UHPLC tracings of fenofibric acid levels in blood and brain, with Figure 3A showing a UHPLC tracing of fenofibric acid levels in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate. [Figure 3B] Figures 3A-3B show representative UHPLC tracings of fenofibric acid levels in blood and brain, and Figure 3B shows a UHPLC tracing of fenofibric acid levels in the brain following oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate.

[0014] [Figure 4A] Figures 4A-4B show representative UHPLC tracings of fenofibric acid levels in blood and brain, with Figure 4A showing a UHPLC tracing of fenofibric acid levels in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate. [Figure 4B] Figures 4A-4B show representative UHPLC tracings of fenofibric acid levels in blood and brain, and Figure 4B shows a UHPLC tracing of fenofibric acid levels in the brain following oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate.

[0015] [Diagram 5] 1 shows representative UHPLC tracings of fenofibric acid levels in blood following oral administration of 3 mg / kg, 10 mg / kg, 30 mg / kg, and 100 mg / kg of the disclosed pharmaceutical compositions containing fenofibrate.

[0016] [Figure 6A] 6A-6F show bar graphs of blood cytokine levels in animals that underwent a 5-day LPS challenge with treatment only on day 1 of LPS challenge, with FIG. 6A showing IL-1β levels. [Figure 6B]6A-6F show bar graphs of blood cytokine levels in animals that underwent a 5 day LPS challenge with treatment only on day 1 of the LPS challenge, and FIG. 6B shows IL-6 levels. [Figure 6C] 6A-6F show bar graphs of blood cytokine levels in animals that underwent a 5 day LPS challenge with treatment only on day 1 of the LPS challenge, and FIG. 6C shows TNFα levels. [Figure 6D] 6A-6F show bar graphs of blood cytokine levels in animals that underwent a 5 day LPS challenge with treatment only on day 1 of the LPS challenge, and FIG. 6D shows MCP-1 levels. [Figure 6E] 6A-6F show bar graphs of blood cytokine levels in animals that underwent a 5 day LPS challenge with treatment only on day 1 of the LPS challenge, and FIG. 6E shows IL-10 levels. [Figure 6F] Figures 6A-6F show bar graphs of blood cytokine levels in animals that received a 5 day LPS challenge with treatment only on day 1 of the LPS challenge, and Figure 6F shows MCP-2 levels. A is saline, B is non-lipid vehicle control, C is lipid vehicle control, D is 30mg / Kg CMF2, E is 100mg / Kg CMF2, F is FENF4, and G is 3mg / kg dexamethasone (*=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control).

[0017] [Figure 7A] 7A-7F show bar graphs of blood cytokine levels in animals treated for 5 days prior to a 5-day LPS challenge, with FIG. 7A showing levels of IL-1β. [Figure 7B] 7A-7F show bar graphs of blood cytokine levels in animals receiving treatment for 5 days prior to LPS challenge for 5 days, and FIG. 7 shows levels of BIL-6. [Figure 7C]7A-7F show bar graphs of blood cytokine levels in animals that received 5 days of treatment prior to 5 days of LPS challenge, and FIG. 7 shows levels of CTNFα. [Figure 7D] 7A-7F show bar graphs of blood cytokine levels in animals receiving treatment for 5 days prior to LPS challenge for 5 days, and FIG. 7 shows levels of DMCP-1. [Figure 7E] 7A-7F show bar graphs of blood cytokine levels in animals receiving treatment for 5 days prior to LPS challenge for 5 days, and FIG. 7 shows levels of EIL-10. [Figure 7F] Figures 7A-7F show bar graphs of blood cytokine levels and Figure 7FMCP-2 levels in animals treated for 5 days prior to LPS challenge (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control).

[0018] [Figure 8A] 8A-8F show bar graphs of brain cytokine levels in animals receiving LPS for 5 days and treated only on day 1 of LPS challenge, with FIG. 8A showing levels of IL-1β. [Figure 8B] 8A-8F show bar graphs of brain cytokine levels in animals receiving LPS for 5 days and treated only on day 1 of LPS challenge, and FIG. 8B shows levels of IL-6. [Figure 8C] 8A-8F show bar graphs of brain cytokine levels in animals receiving LPS for 5 days and treated only on day 1 of LPS challenge, and FIG. 8C shows levels of TNFα. [Figure 8D] 8A-8F show bar graphs of brain cytokine levels in animals receiving LPS for 5 days and treated only on day 1 of LPS challenge, and FIG. 8D shows levels of MCP-1. [Figure 8E]8A-8F show bar graphs of brain cytokine levels in animals receiving LPS for 5 days and treated only on day 1 of LPS challenge, and FIG. 8E shows levels of IL-10. [Figure 8F] Figures 8A-8F show bar graphs of brain cytokine levels in animals receiving LPS for 5 days and treated only on day 1 of LPS challenge, and Figure 8F shows levels of MCP-2 (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control).

[0019] [Figure 9A] 9A-9F show bar graphs of brain cytokine levels in animals that received 5 days of pretreatment 5 days prior to LPS challenge, with FIG. 9A showing levels of IL-1β. [Figure 9B] 9A-9F show bar graphs of brain cytokine levels in animals that received 5 days of pretreatment 5 days prior to LPS challenge, and FIG. 9B shows levels of IL-6. [Figure 9C] 9A-9F show bar graphs of brain cytokine levels in animals that received 5 days of pretreatment 5 days prior to LPS challenge, and FIG. 9C shows levels of TNFα. [Figure 9D] 9A-9F show bar graphs of brain cytokine levels in animals that received 5 days of pretreatment 5 days prior to LPS challenge, and FIG. 9D shows levels of MCP-1. [Figure 9E] 9A-9F show bar graphs of brain cytokine levels in animals that received 5 days of pretreatment 5 days prior to LPS challenge, and FIG. 9E shows levels of IL-10. [Figure 9F] Figures 9A-F show bar graphs of brain cytokine levels in animals that received 5 days of pretreatment 5 days prior to LPS challenge, and Figure 9F shows levels of MCP-2 (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control).

[0020] [Figure 10A] Figures 10A-D show bar graphs representing the percentage levels of IBA-1+ cells and CD-68+ cells per high power field (HPF, x400) in hippocampal and cortical sections of the brain, with Figure 10A showing the percentage levels of cells present in hippocampal sections stained with anti-IBA-1 antibody. [Figure 10B] Figures 10A-D show bar graphs representing the percentage levels of IBA-1+ cells and CD-68+ cells per high power field (HPF, x400) in hippocampal and cortical sections of the brain, and Figure 10B shows the percentage levels of cells present in hippocampal sections stained with anti-CD-68 antibody. [Figure 10C] Figures 10A-D show bar graphs representing the percentage levels of IBA-1+ and CD-68+ cells per high power field (HPF, x400) in hippocampal and cortical sections of the brain, and Figure 10C shows the percentage levels of cells present in cortical sections stained with anti-IBA-1 antibody. [Figure 10D] Figures 10A-D show bar graphs representing the percentage levels of IBA-1+ cells and CD-68+ cells per high power field (HPF, x400) in hippocampal and cortical sections of the brain, and Figure 10D shows the percentage levels of cells present in cortical sections stained with anti-CD-68 antibody (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control, #=p<0.05, ##=p<0.01, ###=p<0.001 vs. CMF2).

[0021] [Figure 11A] 11A-11B show representative UHPLC tracings of cannabidiol levels in blood and brain, where FIG. 11A shows a UHPLC tracing of cannabidiol levels in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing cannabidiol. [Figure 11B]11A-11B show representative UHPLC tracings of cannabidiol levels in blood and brain, and FIG. 11B shows a UHPLC tracing of cannabidiol in the brain following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising cannabidiol.

[0022] [Figure 12] FIG. 1 shows a representative UHPLC tracing of the concentration of mebendazole in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising mebendazole.

[0023] [Figure 13] 1 shows a representative UHPLC tracing of the concentration of aprepitant in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising aprepitant.

[0024] [Figure 14] 1 shows a representative UHPLC tracing of olaparib concentration in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising olaparib. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] The present disclosure discloses pharmaceutical compositions formulated for oral delivery in a manner that the therapeutic compounds present in the pharmaceutical composition are preferentially taken up into the lymphatic system. The pharmaceutical compositions disclosed herein include one or more therapeutic compounds, one or more glycerolipids, and one or more digestive enhancers. The glycerolipids disclosed herein act as stabilizers that promote the dissolution of the therapeutic compounds disclosed herein into solution and / or prevent the therapeutic compounds disclosed herein from precipitating from the pharmaceutical composition. The digestive enhancers disclosed herein, in conjunction with the glycerolipids, increase the solubility of one or more therapeutic compounds in the glycerolipid matrix, increase the absorption of these compounds into the lymphatic system, and increase the availability of these compounds to their therapeutic target. As shown herein, the disclosed pharmaceutical compositions formulated using one or more glycerolipids and one or more digestive enhancers disclosed herein minimize the increase in the bioavailability of the therapeutic compound by maintaining higher levels of the therapeutic compound for extended periods of time, as well as increasing the directed biodistribution of the therapeutic compound to its therapeutic target. Moreover, in many cases, the disclosed pharmaceutical compositions allow the therapeutic compound to reach its maximum concentration in the shortest period of time, in addition to achieving the greatest amount of exposure to its therapeutic target over time. Overall, the disclosed pharmaceutical compositions exhibit superior pharmacokinetic and pharmacodynamic profiles than current formulations of the same therapeutic compound, making the disclosed pharmaceutical compositions more effective and efficacious for their intended uses.

[0026] Almost all digestion of dietary organic macromolecules and absorption of the resulting breakdown products occurs in the small intestine. The luminal wall of the small intestine is lined with many projections called villi, each of which contains intestinal cells called enterocytes. Not only do enterocytes secrete enzymes that digest proteins (polypeptides), carbohydrates (polysaccharides), and fats (lipids), but these cells also absorb amino acid, monosaccharide, and fatty acid breakdown products. Interestingly, however, enterocytes process these breakdown products differently, with amino acids and monosaccharides being taken up by capillaries and transported throughout the body by the blood system, and fatty acids being taken up by blind-ended lymphatic vessels called nipples and then transported throughout the body by the lymphatic system. The disclosed pharmaceutical compositions take advantage of this differential processing by formulating therapeutic compounds that are preferentially processed by enterocytes in a manner that allows these compounds to be taken up and transported through the lymphatic system.

[0027] Dietary lipids typically consumed by mammals comprise 90% triglycerides and small amounts of cholesterol esters and phospholipids. Unlike proteins and carbohydrates, dietary lipids are hydrophobic molecules that cannot dissolve in the fluids present in the lumen of the small intestine, but instead aggregate together to form fat globules. Pancreatic lipase is a water-soluble enzyme that cleaves ester bonds and breaks down lipid triglycerides into fatty acids and glycerol. However, due to its hydrophilicity, lipase remains in the intestinal fluids and is unable to dissolve in fat globules, and therefore can only access and cleave triglycerides located at the surface where the fat globules and intestinal fluids come into contact. To increase the efficiency and rate of cleavage with which lipase can break down lipids in the small intestine, the liver produces a fluid called bile. Bile contains amphipathic molecules, such as bile salts including sodium cholate and sodium chenodeoxycholate, phospholipids including lecithin, and the hydrophobic steroid cholesterol. When bile is excreted into the small intestine, it mixes with the fat globules, and bile salts and phospholipids intercalate with these structures, breaking them down into smaller units called emulsion droplets, while also recruiting amphiphilic molecules called colipases. Colipase is a protein coenzyme that binds lipase to the emulsion droplets and stabilizes the enzyme in its active conformation. Thus, emulsification greatly increases the surface area on which lipase can act on triglycerides, increasing its efficiency and catalytic rate, thereby allowing a sufficient amount of lipid digestion to take place in the small intestine.

[0028] As lipid triglyceride digestion progresses, the resulting free fatty acids, which are both hydrophobic and insoluble in intestinal fluids, associate with bile-derived phospholipids to form droplets called mixed micelles, with a composition of phospholipids and bile salts that encapsulate the free fatty acids. The mixed micelles are approximately 200 to 500 times smaller in size than the emulsion droplets and fuse with the membrane of the enterocyte where the free fatty acids enter the cytosol of these cells. Once inside the enterocyte, the free fatty acids are transported to the lumen of the smooth endoplasmic reticulum, where they are converted back to triglycerides and combined with cholesterol and phospholipids into globular lipid structures. These lipid structures are transported to the rough endoplasmic reticulum where the apoprotein ApoB-48 binds to the surface to form large lipoproteins called chylomicrons. The chylomicrons are then packaged in the Golgi apparatus and exit the basolateral side of the enterocyte via exocytosis. Because chylomicrons are too large to be taken up by blood capillaries, these lipoproteins enter the lymphatic system via the nipple in a process that is dependent on ApoB-48. Chylomicrons then circulate through lymphatic vessels and are discharged into the blood system via the thoracic duct, bypassing the hepatic circulation. Once chylomicrons enter the blood system, these lipoproteins migrate to various extrahepatic tissues, where their triglycerides are hydrolyzed by the activity of lipoprotein lipase, allowing the released free fatty acids and glycerol to be absorbed by the tissues. When most of the triglycerides have been hydrolyzed, chylomicron residues are formed and taken up by the liver, thereby also transporting dietary fat to this organ.

[0029] The natural digestive process relies on the secretion of bile into ingested intestinal contents, emulsification, and their mixing with the intestinal contents to initiate access to other digestive processes such as the activity of lipases. These processes must be completed for the drug to be absorbed. A complete gallbladder response associated with the ingestion of lipids will secrete up to 50-60 mL of bile into the duodenum. The present invention relies on the intimate mixing of the digestive enhancer and the therapeutic compound in the preparation of the pharmaceutical composition disclosed herein, which can then be orally ingested by the patient. The therapeutic compound is then presented to the intestinal lumen in a form that is ready for immediate ingestion. This process is highly efficient because the digestive enhancer is intimately mixed with the formulation lipid excipients. Without wishing to be limited by any theory, the pharmaceutical composition disclosed herein uses ingredients that are products of triglyceride digestion to mimic the conditions brought about by a high-fat diet. This formulation allows one or more therapeutic compounds contained therein to be bundled into micelles along with free fatty acids, which are absorbed by the intestinal cells, which then package the one or more therapeutic compounds into chylomicrons. The therapeutic compound-loaded chylomicrons are then transported by the lymphatic system to their target cells, where the therapeutic compounds are taken up by these cells to exert their beneficial effects.In essence, chylomicrons are employed as a drug delivery system for one or more therapeutic compounds contained in the pharmaceutical compositions disclosed herein.By controlling the composition and amount of one or more glycerolipids and one or more digestive enhancers, the pharmaceutical compositions disclosed herein provide a more consistent and predictable bioavailability of one or more therapeutic compounds disclosed herein that can be achieved by relying on a high-fat meal.

[0030] The pharmaceutical compositions disclosed herein are advantageous for several reasons, all of which ultimately increase the bioavailability and efficacy of one or more therapeutic compounds contained therein. For example, the pharmaceutical compositions disclosed herein deliver their therapeutic compounds via the lymphatic system. The use of the lymphatic system to deliver therapeutic compounds is beneficial for several reasons. First, the lymphatic system avoids pre-systemic metabolism, which reduces the bioavailability of many therapeutic compounds administered using traditional oral delivery approaches. Also referred to as the first-pass effect or first-pass metabolism, a therapeutic compound absorbed by the digestive system must first enter the hepatic portal system before reaching the systemic circulation. While in the hepatic portal system, the therapeutic compound can be metabolized by hepatic enzymes in the liver, which reduces the amount of therapeutic compound that enters the systemic circulation. Thus, delivery of a therapeutic compound via the lymphatic system acts as a bypass to the hepatic portal system for therapeutic compounds susceptible to hepatic metabolism. The lymphatic uptake system represents an attractive opportunity for preferential delivery of drugs. However, small water-soluble molecules that obey the rules of paracellular absorption (e.g., the rules of Lipinski's rule) are not ideal substrates for lymphatic uptake. Even when absorbed via lymphatic uptake, there are often additional highly lipophilic molecules that are poorly and variably bioavailable. The present invention uses a broad family of digestive enhancers in lipid delivery systems to enable the effective delivery of both small molecule Lipinski compatible drugs and highly lipophilic drugs via the lymphatic uptake route.

[0031] In addition, the lymphatic administration route can assist in the direct delivery of the therapeutic compound to its target cells, thereby increasing its bioavailability and decreasing its clearance rate. For example, the therapeutic compound-loaded chylomicrons transported to the lymphatic system are drained into the thoracic artery and circulate throughout the body via the arterial system to reach the capillary bed, where the therapeutic compound-loaded chylomicrons are extracted into the surrounding tissues for uptake by the target cells. The therapeutic compound-loaded chylomicrons that are not taken up by the target cells and removed from the extracellular environment by the interstitial fluid are taken up by lactate, transported by the lymphatic system, and drained into the thoracic artery, where the therapeutic compound-loaded chylomicrons are recirculated systemically again throughout the body. Such lymphatic-based administration results in more therapeutic compounds being delivered to various systems, organs, and tissues due to the avoidance of the hepatic portal system mentioned above. In addition, because more therapeutic compounds enter the general circulatory system, their elimination, i.e., metabolism and excretion, is prolonged, thereby decreasing the clearance rate of the therapeutic compounds and effectively increasing their half-life.

[0032] Another advantage of the disclosed pharmaceutical composition is the use of chylomicrons to selectively biodistribute one or more therapeutic compounds contained therein to immune cells, such as macrophages and dendritic cells. For example, there are several processes by which macrophages can take up chylomicrons. First, macrophages circulating in lymph and blood secrete lipoprotein lipase, and chylomicrons are the substrate for this enzymatic activity, resulting in the uptake of chylomicron proteins and lipids, and thus any therapeutic compounds contained within the chylomicron. Furthermore, the exogenous lipoprotein metabolic pathway, through a series of processing events, converts chylomicrons into LDL particles, which are oxidized by ROS to generate oxidized LDL particles. The FAT / CD36 scavenger receptors located on the membrane of macrophages bind and endocytose these oxidized LDL particles, including any therapeutic compounds contained therein. Finally, these therapeutic compound-loaded macrophages are directed to cells undergoing pathological damage where they can deliver the therapeutic compound to these damaged cells.

[0033] Furthermore, when processed into micelles in the small intestine, the components of the disclosed pharmaceutical compositions are believed to mimic pathogen-associated molecular patterns (PAMPs). Absorption of these micelles by the gut-associated lymphoid tissue (GALT) of the small intestine leads to subsequent uptake by immune cells such as macrophages and dendritic cells through a pattern recognition receptor-mediated process. In addition, since these micelles share structural similarities with chylomicrons, it is believed that these micelles can also be taken up via the process of macrophage lipoprotein lipase described above.

[0034] The disclosed pharmaceutical compositions are also advantageous because the ingredients used in their formulation mimic signals that induce bile and pancreatic lipoprotein lipase secretion, increasing the rate of micelle formation and enhancing the rate of enterocyte absorption of the micelles beyond that achieved with the use of digestive enhancers in the formulation alone. Such characteristics increase the rate and amount of therapeutic compound that enters the lymphatic system and therefore its bioavailability.

[0035] In addition to preferential uptake into lymphatic system and selective biodistribution to immune cells, the disclosed pharmaceutical composition has several additional advantages.For example, the pharmaceutical composition disclosed herein can be used to formulate a wide range of poorly water-soluble or hydrophobic therapeutic compounds that have previously proven difficult to formulate in a therapeutically effective manner, for example, due to their insolubility or instability in solution resulting in precipitation.In addition, it has been surprisingly found that significantly higher concentrations of poorly water-soluble or hydrophobic therapeutic compounds can be formulated into the pharmaceutical composition disclosed herein compared to currently known formulations.In addition, the pharmaceutical composition disclosed herein is also useful for formulating a wide range of hydrophilic therapeutic compounds, and such formulations dramatically increase the dissolution rate and bioavailability of these hydrophilic compounds.

[0036] Yet another advantage of the disclosed pharmaceutical compositions is the enhanced specificity of one or more therapeutic compounds for their cellular targets. Chylomicrons contain membrane-bound proteins that function as ligands that associate with their cognate receptors located on the membrane surface of cells. One such ligand for these large lipoprotein particles is a protein that interacts with lipid transfer proteins. When therapeutic compound-loaded chylomicrons are shed for absorption, cells that express high levels of lipid transfer proteins on their cell membranes preferentially bind and internalize these lipoprotein particles. For example, the brain has high levels of lipid transfer proteins on its cell membranes, allowing it to cross the blood-brain barrier, and other epithelial tissues such as the choroid plexus. This mechanism thereby increases the efficacy of these compounds. Other cells that express high levels of lipid transfer proteins on their cell membranes include immune cells, cardiac cells, adipocytes, liver cells and cancer cells. Cardiac cells express high levels of lipid transfer proteins on their surface, and therefore, we can expect increased cardiotoxicity for therapeutic compounds delivered via lymphatic routes. However, cardiotoxicity of therapeutic compounds is generally associated with high C maxConcentrations of free compounds can cause cardiotoxicity, resulting in GPCR or ion channel-related pathology. Surprisingly, therefore, lipid delivery of therapeutic compounds can result in lower cardiac toxicity than expected, as these targets are protected from high concentrations of free compounds, because they are only slowly released from the chylomicron phase. Thus, the use of the pharmaceutical compositions disclosed herein can also be associated with reduced cardiac side effects and reduced toxicity. Furthermore, upon ingestion, the therapeutic compounds remain embedded in the oily / fatty excipient, limiting the opportunity for the compounds to solubilize in aqueous intestinal contents, thereby avoiding contact toxicity, such as gastric erosion and other local damage or harm. In addition to avoiding first-pass metabolism and local toxicity, enhanced uptake through the lymphatic pathway also minimizes the contact and availability of free therapeutic compounds further down the digestive tract. In this way, interactions and disruption of the gut microbiota can be minimized. This is particularly beneficial when using this technology with antibacterial agents. Furthermore, the anatomy of the lymphatic system allows the lungs to be effectively targeted with the appropriate agents. For example, anti-inflammatory, anti-fibrotic, antibacterial and bronchodilator drugs could be considered for targeting by lymphatic delivery using this technology.

[0037] Additionally, the disclosed pharmaceutical compositions are distinct from current surfactant-based formulations, such as macroemulsions, microemulsions, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS), solid lipid nanoparticles (SLN), liposomes, and lipoplexes. The disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions, and therefore avoid the side effects associated with these formulations, such as destabilizing the membrane lining the stomach and causing irritation. Additionally, the disclosed pharmaceutical compositions avoid manufacturing issues associated with current surfactant-based formulations, such as formulation handling issues and lack of predictive in vitro testing. The disclosed pharmaceutical compositions also avoid issues associated with current surfactant-based formulations, including, for example, in vivo drug precipitation, limited lymphatic uptake, and lack and oxidation of unsaturated fatty acids. Surprisingly, by mimicking the microenvironment of mixed micelles, the disclosed pharmaceutical compositions completely bypass the dissolution phase of drug uptake, resulting in significantly higher bioavailability of one or more therapeutic compounds contained therein. Unlike the self-emulsifying systems described above, the formulations disclosed herein are designed to avoid the formation of stable emulsions and do not undergo spontaneous emulsification when added to water (exhibiting the ouzo effect). Rather, when added to water, these materials are apparently immiscible.

[0038] Pharmaceutical Compositions Aspects of the present specification partially disclose compositions. The compositions disclosed herein are generally administered as pharma- ceutically acceptable compositions. As used herein, the term "pharma-ceutically acceptable" refers to any molecular entity or composition useful for preparing pharmaceutical compositions that are generally safe, non-toxic, and not biologically or otherwise undesirable, including any molecular entity or composition that is acceptable for veterinary and human pharmaceutical use. As used herein, the term "pharma-ceutically acceptable composition" is synonymous with "pharmaceutical composition" and refers to a combination of one or more therapeutic compounds disclosed herein that are combined with one or more glycerolipids, one or more digestive enhancers, and other components disclosed herein to form a product that is administered to an individual. The pharmaceutical compositions disclosed herein are useful for medical and veterinary applications. The pharmaceutical compositions may be administered to an individual alone or in combination with other supplementary active ingredients, agents, drugs, or hormones.

[0039] The present disclosure discloses pharmaceutical compositions useful for formulating a wide variety of therapeutic compounds. In some embodiments, the pharmaceutical compositions disclosed herein include a) one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein include a) one or more therapeutic compounds, b) one or more glycerolipids, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more glycerolipids, c) one or more bile acids and / or one or more bile salts, and d) one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more glycerolipids, c) one or more bile acids and / or one or more bile salts, d) one or more phospholipids, and e) one or more free C 14-24In all of the above embodiments, the one or more therapeutic compounds disclosed herein can include one or more hydrophilic therapeutic compounds, one or more poorly water-soluble or hydrophobic therapeutic compounds, or any combination thereof.

[0040] In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, and d) one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, d) one or more phospholipids, and e) one or more free C 14-24In all of the above embodiments, the one or more therapeutic compounds disclosed herein can include one or more hydrophilic therapeutic compounds, one or more poorly water-soluble or hydrophobic therapeutic compounds, or any combination thereof.

[0041] In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and / or one or more bile salts, and d) one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and / or one or more bile salts, d) one or more phospholipids, and e) one or more free C 14-24 In all of the above embodiments, the one or more therapeutic compounds disclosed herein can include one or more hydrophilic therapeutic compounds, one or more poorly water-soluble or hydrophobic therapeutic compounds, or any combination thereof.

[0042] The pharmaceutical compositions disclosed herein are formulated as anhydrous solids, solid dispersions, or molecular dispersions. Thus, the formulations of the disclosed pharmaceutical compositions do not include any water. Furthermore, as mentioned above, the disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions. Thus, the pharmaceutical compositions disclosed herein behave like fats and oils in an aqueous environment, and maintain their hydrophobic lipid properties when necessary to break down lipid digestion processes for absorption. Emulsion occurs only when exposed to pancreatic juices from the small intestine. One reason is that the one or more glycerolipids and one or more digestive enhancers used are not amphiphilic enough to initiate emulsification, and require the action of bile secreted by the gallbladder during the digestive process for these components to contribute to the formation of micellar structures. Another reason is that the bile acids, fatty acid surfactants, phospholipids, and any other digestive enhancers are all present individually and in combination below the critical micelle concentration required for emulsification to occur.

[0043] therapeutic compounds Aspects of the present specification disclose, in part, therapeutic compounds. Therapeutic compounds are compounds that provide pharmacological activity or other direct effects in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the human or animal body. Therapeutic compounds include both synthetic small molecule therapeutic compounds and synthetic peptides, biological therapeutic compounds manufactured, extracted, or semi-synthesized from biological sources, including live drugs, used in vaccines, whole blood, blood components, allergens, somatic cells, gene therapy, tissues, recombinant therapeutic proteins, and cell therapy. Non-limiting examples of biologics include blood factors such as Factor VIII and Factor IX, thrombolytic agents like tissue plasminogen activator, hormones like insulin, glucagon, growth hormone, gonadotropins, hematopoietic growth factors like erythropoietin, colony stimulating factors, immunotherapeutics, interferons like interferon-α, interferon-β and interferon-γ, interleukin system products like interleukin-2, vaccines like influenza vaccine, SAR-CoV-2 vaccine, HIV vaccine, hepatitis B vaccine, hepatitis C vaccine and malaria vaccine, monoclonal antibodies, tumor necrosis factors and therapeutic enzymes.

[0044] Non-limiting examples of therapeutic compounds include pharmaceutical active agents or components, diagnostic agents or components, cosmetic active agents or components, and nutraceutical active agents or components. The therapeutic compounds disclosed herein can be used in the form of a salt, for example a pharma- ceutically acceptable salt of hydrochloride, a solvate or a solvate. In addition, the therapeutic compounds disclosed herein can be provided as racemates or as individual enantiomers, including R- or S-enantiomers. Thus, the therapeutic compounds disclosed herein can include only the R-enantiomer, only the S-enantiomer, or a combination of both the R-enantiomer and the S-enantiomer of the therapeutic compound. The therapeutic compounds disclosed herein can be hydrophilic therapeutic compounds or hydrophobic therapeutic compounds.

[0045] The pharmaceutical compositions disclosed herein may include one or more therapeutic compounds based on the Biopharmaceutical Classification System (BCS) Class I-IV drugs. The BCS is a scientific framework for classifying drug substances based on their minimum aqueous solubility in the pH range of 1 to 7.5, absorbed dose and human fraction or intestinal membrane permeability, see USDepartment of Health and Human Services Food and Drug Administration Center for Evaluation and Research (CDER), Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, Guidance for Industry (2017), which is incorporated herein by reference in its entirety. When combined with the dissolution of the drug product, the BCS takes into account three major factors that govern the rate and extent of drug absorption from IR solid oral dosage forms: (1) dissolution, (2) solubility, and (3) intestinal permeability. The system classifies drugs into four classes according to their permeability and solubility. BCS class I drugs are therapeutic compounds that have high solubility and high permeability and are generally completely absorbed. BCS class II drugs are therapeutic compounds that have low solubility and high permeability and are completely absorbed if in solution. BCS class III drugs are therapeutic compounds that have high solubility and low permeability and are difficult to completely absorb, even though the drug is in solution (high dissolution rate). BCS class IV drugs are therapeutic compounds that have low solubility and low permeability, are difficult to put into solution and are poorly absorbed when in solution.Subclassifications have also been proposed based on whether a therapeutic compound from BCS class I or III is an acid, a base, or neutral, as described in Tsume, et al., The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC, Eur. J. Pharm. Sci. 57:152-163 (2014), which is incorporated by reference in its entirety.

[0046] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class I therapeutic compounds, BCS class II therapeutic compounds, BCS class III therapeutic compounds, BCS class IV therapeutic compounds, or any combination thereof. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class I therapeutic compounds. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class II therapeutic compounds. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class III therapeutic compounds. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class IV therapeutic compounds.

[0047] The pharmaceutical compositions disclosed herein may comprise one or more hydrophilic therapeutic compounds.The hydrophilic therapeutic compounds disclosed herein include amphiphilic therapeutic compounds, and are water-soluble compounds with considerable or substantial water solubility.In some embodiments, the hydrophilic therapeutic compounds disclosed herein have an inherent water solubility (i.e., water solubility in non-ionized form) of, for example, at least 0.1% (by weight), at least 0.5% (by weight), at least 1% (by weight), or more typically at least 10% (by weight).

[0048] The pharmaceutical compositions disclosed herein may comprise one or more hydrophobic therapeutic compounds.The hydrophobic therapeutic compounds disclosed herein include lipophilic therapeutic compounds, which are poorly water-soluble compounds with little or no water solubility.In some embodiments, the poorly water-soluble or hydrophobic therapeutic compounds disclosed herein have an inherent water solubility (i.e., water solubility in non-ionized form) of, for example, at most 1% (by weight), at most 0.5% (by weight), at most 0.1% (by weight), and more typically at most 0.01% (by weight).

[0049] The therapeutic compounds disclosed herein may have a logP value greater than 0. As used herein, the term "logP value" refers to the logarithm (base 10) of the partition coefficient (P) of a compound and is a measure of lipophilicity. Typically, P is defined as the ratio of the concentrations of an ionized compound in two phases of a mixture of two immiscible solvents at equilibrium. Thus, logP=Log10(P), where P=[solute in immiscible solvent 1] / [solute in immiscible solvent 2]. The logP value of a compound is constant for any given solvent pair, with respect to the organic and aqueous phases, and the value can be empirically determined by one of several phase partitioning methods known to those skilled in the art, including, for example, shake flask assay, HPLC assay, and interface assay between two immiscible electrolyte solutions (ITIES).

[0050] In some embodiments, a therapeutic compound disclosed herein may have a logP value that indicates that the compound is substantially soluble in a formulation of a pharmaceutical composition disclosed herein. In one embodiment, a therapeutic compound disclosed herein may have a logP value that indicates that the compound is, for example, at least 50% soluble, at least 60% soluble, at least 70% soluble, at least 80% soluble, or at least 90% soluble in a formulation of a pharmaceutical composition disclosed herein. In one embodiment, a therapeutic compound disclosed herein may have a logP value that indicates that the compound is, for example, about 50% to about 100% soluble, about 60% to about 100% soluble, about 70% to about 100% soluble, about 80% to about 100% soluble, or about 90% to about 100% soluble in a formulation of a pharmaceutical composition disclosed herein.

[0051] In one embodiment, a therapeutic compound disclosed herein may have a logP value of, for example, at least 1.1, at least 1.2, at least 1.4, at least 1.6, at least 1.8, at least 2.0, at least 2.2, at least 2.4, at least 2.6, at least 2.8, at least 3.0, at least 3.2, at least 3.4, or at least 3.6. In one embodiment, a therapeutic compound disclosed herein may have a logP value of, for example, at most 1.1, at most 1.2, at most 1.4, at most 1.6, at most 1.8, at most 2.0, at most 2.2, at most 2.4, at most 2.6, at most 2.8, at most 3.0, at most 3.2, at most 3.4, or at most 3.6. In one embodiment, a therapeutic compound disclosed herein may have a logP value within the range of, for example, 1.0-4.0, 1.1-4.0, 1.2-4.0, or 1.3-4.0, 1.4-4.0, 1.5-4.0, 1.6-4.0, 1.8-4.0, 2.0-4.0, 2.1-4.0, 2.2-4.0, or 2.3-4.0, 2.4-4.0, 2.5-4.0, 2.6-4.0, 2.8-4.0, 3.0-4.0, or between 3.1-4.0, 3.2-4.0, 3.3-4.0, 3.4-4.0, 3.5-4.0, or 3.6-4.0. In one embodiment, a therapeutic compound disclosed herein may have a logP value ranging, for example, between 1.0-3.0, 1.1-3.0, 1.2-3.0, or 1.3-3.0, 1.4-3.0, 1.5-3.0, 1.6-3.0, 1.8-3.0, 2.0-3.0, 2.1-3.0, 2.2-3.0, or 2.3-3.0, 2.4-3.0, 2.5-3.0, 2.6-3.0, or 2.8-3.0. In one embodiment, a therapeutic compound disclosed herein may have a logP value ranging, for example, between 1.0-2.0, 1.1-2.0, 1.2-2.0, or 1.3-2.0, 1.4-2.0, 1.5-2.0, 1.6-2.0, or 1.8-2.0.

[0052] The therapeutic compounds disclosed herein may have a polar surface area that is hydrophobic. As used herein, the term "polar surface area" refers to the total surface area over all polar atoms in the structure of the compound and is a measure of hydrophobicity. Typically, these polar atoms include, for example, oxygen, nitrogen, and hydrogen attached thereto. In one embodiment, the therapeutic compounds disclosed herein have a surface area of, for example, 8.0 nm 2 Less than 7.0 nm 2 Less than 6.0 nm 2 Less than 5.0 nm 2 Less than 4.0 nm 2 , or 3.0 nm 2 In one embodiment, the therapeutic compounds disclosed herein may have a polar surface area of ​​less than, for example, 3.0 nm 2 ~6.5nm 2 , 3.0 nm 2 ~6.0 nm 2 , 3.0 nm 2 ~5.5nm 2 , 3.0 nm 2 ~5.0 nm 2 , 3.0 nm 2 ~4.5nm 2 , 3.5 nm 2 ~6.5nm 2 , 3.5 nm 2 ~6.0 nm 2 , 3.5 nm 2 ~5.5nm 2 , 3.5 nm 2 ~5.0 nm 2 , 3.5 nm 2 ~4.5nm 2 , 4.0 nm 2 ~6.5nm 2 , 4.0 nm 2 ~6.0 nm 2 , 4.0 nm 2 ~5.5nm 2 , or 4.0 nm 2 ~5.0 nm 2 , 4.0 nm 2 ~4.5nm 2 , or 4.5 nm 2 ~5.5nm 2In one embodiment, the poorly water-soluble or hydrophobic therapeutic compounds disclosed herein may have a polar surface area ranging between, for example, 2.0 nm 2 ~6.5nm 2 , 2.0 nm 2 ~6.0 nm 2 , 2.0 nm 2 ~5.5nm 2 , 2.0 nm 2 ~5.0 nm 2 , 2.0 nm 2 ~4.5nm 2 , 2.5 nm 2 ~6.5nm 2 , 2.5 nm 2 ~6.0 nm 2 , 2.5 nm 2 ~5.5nm 2 , 2.5 nm 2 ~5.0 nm 2 , or 2.5 nm 2 ~4.5nm 2 The polar surface area may range between 0.1 and 1.

[0053] In some embodiments, the therapeutic compounds disclosed herein are therapeutic compounds that contain an organic acid functional group, such as a carboxylic acid functional group or a sulfonic acid functional group. Examples of the disclosed therapeutic compounds that contain an organic acid functional group include free acid forms of the therapeutic compounds (i.e., therapeutic compounds with free organic acids) and salt forms of the therapeutic compounds (i.e., therapeutic compounds with organic acid salts). Organic acid salt forms of the therapeutic compounds include any therapeutic compound that is combined with an alkali metal, such as lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or an alkaline earth metal, such as beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).

[0054] In some embodiments, the therapeutic compound disclosed herein is a therapeutic compound that comprises an organic base functional group, for example, an amine functional group.The disclosed therapeutic compound that comprises an organic base functional group includes an example of a therapeutic compound that comprises an organic base functional group that can donate ions.In some embodiments, the therapeutic compound that comprises an organic base functional group that can donate ions is a therapeutic compound that comprises an amine functional group that can donate ions, for example, but not limited to, primary amine, secondary amine, tertiary amine, amide, amidine, amide, amino, imidate, imide, imine, imino, iminohydroxyl and quaternary salt.

[0055] Non-limiting examples of therapeutic compounds include those classified in the United States Pharmacopeia (USP), including analgesics (including opioids and non-opioids), anesthetics, antimicrobials (including antibiotics), anticonvulsants, anti-dementia drugs, antidepressants, antidotes and antitoxins, antiemetics, antifungals, anti-inflammatory drugs (including corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and nonsteroidal anti-inflammatory drugs (NSAIDs)), antimigraine drugs, antimyasthenic drugs, anti-fungal drugs, antineoplastic drugs, anti-parasitic drugs, anti-Parkinson drugs, antipsychotic drugs, antiviral drugs (including HIV antiretrovirals and direct acting Hepatitis C drugs), anti-anxiety (antianxiety drugs), bipolar drugs, blood glucose regulating drugs (including insulin and other diabetes drugs), blood products (including anticoagulants), cardiovascular drugs (including beta-blockers, ACTH drugs, and the like). E inhibitors, and lipid management agents such as statins and PPAR agonists), central nervous system active agents (including amphetamines), dental and oral agents, dermatological (skin) agents, enzyme replacement agents, gastrointestinal agents (including H2 blockers and proton pump inhibitors), urogenital (reproductive system and urinary tract) agents, hormonal agents (adrenal glands, pituitary gland, prostaglandins, sex hormones, e.g., estrogen, testosterone, and anabolic steroids, and thyroid), hormonal suppressants (adrenal glands, parathyroid gland, pituitary gland, sex hormones, and thyroid), immunological agents, inflammatory bowel disease agents, metabolic bone disease agents, inotropic agents, ophthalmic agents, otic agents, airway agents (including antihistamines and bronchodilators), sedatives and hypnotics, skeletal muscle relaxants, and therapeutic nutrients, minerals and electrolytes.

[0056] Non-limiting examples of therapeutic compounds include 5-alpha-reductase inhibitors, 5-aminosalicylates, 5HT3 receptor antagonists, adamantanes, corticosteroids, corticosteroid inhibitors, hypertensive emergencies, pulmonary hypertension, aldosterone receptor antagonists, alkylating agents, allergens, alpha-glucosidase inhibitors, alternative medicines, herbicides, aminoglycosides, aminopenicillins, aminosalicylates, amphetamines, AMPA receptor antagonists, amylin analogs, analgesics, androgens, anabolic steroids, angiotensin-converting enzyme (ACE) inhibitors, androgen ... angiotensin II inhibitors, angiotensin II receptor blockers, appetite suppressants, antacids, antiadrenergics, antiandrogens, antianginals, antiarrhythmics, antiasthmatics, anxiolytics, antibiotics, anticholinergics, anticoagulants, anticoagulant reversers, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheal agents, antidotes, antiemetics, antifungal agents, antigonadotropins, antigout agents, anthelmintics, antihistamines, antihyperlipidemic agents, antihypertensive agents, antihyperuricemic agents, anti-infective agents, antimalarials, antimaniacs, antimetabolites, antimigraine agents, antineoplastic agents, antineoplastic antidotes, antineoplastic interferons, antiparkinsonians Antiplatelet agents, Antipseudomonal agents, Antipsoriatic agents, Antipsychotic agents, Antirheumatic agents, Antirosacea agents, Antiseptics and fungicides, Antispasmodics, Antithyroid agents, Antidotes and antitoxins, Antituberculous agents, Antitussives, Antivertigo agents, Antivirals, Antiviral boosters, Anxiolytics, Sedatives and hypnotics, Aromatase inhibitors, Astringents, Atypical antipsychotics, Azoles, Barbiturates, BCR-ABL tyrosine kinase inhibitors, Benzodiazepines, Beta blockers, Beta-adrenergic blockers, Beta-lactamase inhibitors, Bile acid sequestrants, Bisphosphonates, Bone morphogenetic proteins, Bone resorption inhibitors, Bronchodilators Combinations, Bronchodilators, BTK Inhibitors, Calcimimetics, Calcineurin Inhibitors, Calcitonin, Calcium Channel Blockers, Carbapenems, Carbonic Anhydrase Inhibitors, Cardiac Stress Agents, Cardioselective Beta Blockers, Cardiovascular Agents, Catecholamines, CDK4 / 6 Inhibitors, Central Nervous System Agents, Cephalosporins, Earwax Removers, CFTR Enhancers, CGRP Inhibitors, Chelators, Chemokine Receptor Antagonists, Chloride Channel Activators, Cholesterol Absorption Inhibitors, Cholinergic Agonists, Cholinergic Muscle Stimulants, Cholinesterase Inhibitors, Chronotropes, CNS Stimulants, Coagulation Modulators,Colony stimulating factors, corticosteroids, corticotropins, coumarins and indanediones, COX-2 inhibitors, decongestants, diarylquinolines, dibenzazepines, diagnostic dyes, dipeptidyl peptidase 4 inhibitors, disease modifying antirheumatic drugs (DMARDs), diuretics, echinocandins, EGFR inhibitors, erythropoietic agents, estrogen receptor antagonists, estrogens, expectorants, factor Xa inhibitors, fibrotic acid derivatives, first generation cephalosporins, fourth generation cephalosporins, functional bowel disorder agents, gallstone dissolution aids, gamma aminobutyric acid analogues, gamma aminobutyric acid reuptake inhibitors. Gastrointestinal agents, Genitourinary tract agents, GI stimulants, Glucocorticoids, Glucose-elevating agents, Glycoprotein platelet inhibitors, Glycylcyclines, Gonadotropin-releasing hormone, Gonadotropin-releasing hormone antagonists, Gonadotropins, Class I antiarrhythmics, Class II antiarrhythmics, Class III antiarrhythmics, Class IV antiarrhythmics, Class V antiarrhythmics, Growth hormone receptor blockers, Growth hormone, Guanylate cyclase C agonists, H. pylori eradication agents, H2 antagonists, Hedgehog pathway inhibitors, Hematopoietic stem cell mobilizers, Heparin antagonists, Heparin, HER2 inhibitors, Herbal products, Histone deacetylase inhibitors, Hormones, Hydantoins, Hydrazide derivatives, Immunologic agents, Immunostimulants, Immunosuppressants, Impotence agents, Incretin mimetics, Cardiotonic agents, Insulin, Insulin-like growth factors, Integrase strand transfer inhibitors, Interferons, Interleukin inhibitors, Interlo Ikin, intravenous nutrition products, investigational drugs, iodized contrast agents, iron products, ketolides, reprostatin, leukotriene modifiers, lincomycin derivatives, local injectable anesthetics, lymphatic stains, macrolide derivatives, macrolides, magnetic resonance imaging contrast agents, malignant photosensitizers, mast cell stabilizers, meglitinides, melanocortin receptor agonists, metabolic agents, methylxanthines, mineralocorticoids, minerals and electrolytes, mitotic inhibitors, monoamine oxidase inhibitors, mTOR inhibitors, mucolytic agents, multikinase inhibitors, muscle relaxants, mydriatics, neprilysin inhibitors, neuraminidase inhibitors, neuromuscular blockers, neural potassium channel openers, NHE3 inhibitors, nicotinic acid derivatives, NK1 receptor antagonists, non-opioids, NNRTIs, non-cardioselective beta blockers, non-sulfonylureas, non-steroidal anti-inflammatory drugs, nootropic agents, NS5A inhibitors,Nucleoside reverse transcriptase inhibitors (NRTIs), nutraceuticals, nutritional supplements, ophthalmic products, opioids, otic products, oxazolidinediones, parathyroid hormone and analogs, PARP inhibitors, PCSK9 inhibitors, penicillins, peripheral opioid receptor antagonists, peripheral opioid receptor mixed agonists / antagonists, peripheral vasodilators, peripherally acting antiobesity agents, phenothiazines, phenylpiperazines, phosphate binders, PI3K inhibitors, plasma expanders, platelet aggregation inhibitors, platelet stimulants, polyenes, probiotics Otics, Progesterone receptor modulators, Progestins, Prolactin inhibitors, Prostaglandin D2 antagonists, Protease inhibitors, Protease-activated receptor-1 antagonists, Proteasome inhibitors, Proton pump inhibitors, PPAR agonists, Psoralens, Psychotherapeutic agents, Purine nucleosides, Pyrrolidines, Quinolones, Radiocontrast agents, Radioadjuvants, Radioagents, Radioconjugates, Radiopharmaceuticals, Renal replacement solutions, Renin inhibitors, Respiratory agents, Rifamycin derivatives, Salicylates, Sclerosing agents agents, second generation cephalosporins, selective estrogen receptor modulators, selective immunosuppressants, selective phosphodiesterase-4 inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonergic neuroenteric modulators, sex hormones, SGLT-2 inhibitors, skeletal muscle relaxants, smoking cessation agents, somatostatin and somatostatin analogues, spermicides, statins, streptogramins, streptomycete derivatives, succinimides, sulfonamides, sulfonamides phenylureas, sympathomimetic amines, synthetic ovulation stimulants, tetracyclines, therapeutic radiopharmaceuticals, thiazides, thiazolidinediones, thioxanthenes, thioxanthones, third generation cephalosporins, thrombin inhibitors, thrombolytics, thyroid drugs, TNFα inhibitors, tocolytics, transthyretin stabilizers, triazines, urea cycle disruptors, urinary pH regulators, uterotonics, vasodilators, vasopressin antagonists, vasoconstrictors, VEGF / VEGFR inhibitors, thickeners, vitamins, and VMAT2 inhibitors.

[0057] The therapeutic compound disclosed herein can be a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs are a large group of therapeutic compounds that have analgesic, anti-pain and anti-pyretic properties. NSAIDs can be classified based on their chemical structure or mechanism of action. NSAIDs can be non-selective cyclooxygenase (COX) inhibitors, selective cyclooxygenase 1 (COX1) inhibitors, or selective cyclooxygenase 2 (COX2) inhibitors. Non-limiting examples of NSAIDs include acetate derivatives NSAIDs, enolate derivatives NSAIDs, fenamate derivatives NSAIDs, propionate derivatives NSAIDs, pyrazolone derivatives NSAIDs, salicylate derivatives NSAIDs, and NSAIDs can be profen.

[0058] Examples of suitable acetic acid derivative NSAIDs include, but are not limited to, aceclofenac, acemetacin, aclofenac, amfenac, alclofenac, bendazac, bromfenac, bufexamac, bumadizone, cinmetacin, clometacin, diclofenac, difenpyramide, etodolac, felbinac, fenclofenac, fentiazac, glucametacin, indometacin, indomethacin, indomethacin farnesyl, ketorolac, lonazolac, mofezolac, nabumetone, oxametacin, oxyindanac, proglumetacin, sulindac, sulindac sulfide, tolmetin, zidometacin, and zomepirac. Examples of suitable enolic acid (oxicam) derivative NSAIDs include, but are not limited to, ampiroxicam, droxicam, isoxicam, lornoxicam, meloxicam, piroxicam and tenoxicam. Examples of suitable fenamic acid derivative NSAIDs include, but are not limited to, etofenamic acid (etofenamate), floctafenic acid (floctafenate), flufenamic acid (flufenamate), meclofenamic acid (meclofenamate), mefenamic acid (mefenamate), morniflumic acid (morniflumate), niflumic acid (niflumate), talflumic acid (talflumate), tolfenamic acid (tolfenamate). Examples of suitable propionic acid derivative NSAIDs include, but are not limited to, aluminoprofen, benoxaprofen, bucloxic acid (brucloxate), butibufen, carprofen, dexibuprofen, dexidoprofen, dexketoprofen, fenbufen, fenoprofen, flunoxaprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen, ketoprofen, loxoprofen, miloprofen, naproxen, naproxinod, oxaprozin, piprofen, pranoprofen, suprofen, tarenflurol, tepoxalin, tiaprofenic acid (tiaprofenic acid) and vedaprofen.Examples of suitable pyrazolone derivative NSAIDs include, but are not limited to, aminophenazone, ampyrone, metamizole (dipyrone), nifenazone, phenoazone and propyphenazone. Examples of suitable salicylate derivative NSAIDs include, but are not limited to, acetylsalicylic acid (asprin), aloxyprine, benorylate, carbasalate calcium, diflucinal, dipyrocetyl, ethenzamide, guacetisal, magnesium salicylate, mesalazine (5-aminosalicylic acid), methyl salicylate, salacetamide, salicin, salicylamide, salicylate (salicylic acid), salalate, sodium salicylate and trifludar. Examples of suitable selective COX-2 inhibitors include, but are not limited to, celecoxib, etoricoxib, firocoxib, lumiracoxib, meloxicam, parecoxib, rofecoxib, and valdecoxib.

[0059] The therapeutic compound disclosed herein can be a paracetamol-type therapeutic compound. Examples of suitable paracetamol-type therapeutic compounds include, but are not limited to, acetanilide, bucetin, butacetin, paracetamol (acetaminophen), parapropamol, phenacetin and propacetamol.

[0060] The therapeutic compound disclosed herein can be a peroxisome proliferator-activated receptor (PPAR) agonist. Examples of suitable PPAR agonists include, but are not limited to, PPARα agonists, PPARγ agonists, PPARδ agonists, and dual PPAR-α / γ agonists (or glitazars).

[0061] The therapeutic compound disclosed herein can be a PPARα agonist.Suitable examples of PPARα agonists include, but are not limited to, 15-H-eicosatetraenoic acid, 15-hydroperoxy-eicosatetraenoic acid, aleglitazar, aluminum clofibrate, arachidonic acid, bezafibrate, clofibrate, CP-775146, daidzein, DHEA (prasterone), elafibranor, etomoxir, fenofibrate, genistein, gemfibrozil, GW-7647, lanifibranor, leukotriene B 4 , LG-101506, LG-100754, lobeglitazone, muraglitazar, oleiethanolamide, palmitoylethanolamide, pemafibrate, perfluorononanoic acid, perfluorooctanoic acid, pioglitazone, saraglitazone, soderglitazar, tesaglitazar, tetradecylthioacetic acid, troglitazone, and WY-14643.

[0062] The therapeutic compound disclosed herein can be a PPARγ agonist. Examples of suitable PPARγ agonists include, but are not limited to, 5-oxo-eicosatetraenoic acid, 5-oxo-15-hydroxy-eicosatetraenoic acid, 15-deoxy-Δ12,14-prostaglandin J2, 15-eicosatetraenoic acid, 15-hydroperoxy-eicosatetraenoic acid, aleglitazar, arachidonic acid, balaglitazone, berbeberine, bezafibrate, cannabidiol, sevoglitazo, ciglitazone, daidzein, darglitazone, edaglitazone, efatudazone, englitazone, etalosib, farglitazo, genistein, GW-1929, ibuprofen, glycerol, imiglitazoI, indeglitazoI, lanfiazol, LG-100268, LG-100754, LG-101506, lobeglitazone, muraglitazar (muroglitazar), nTZDpa, naveglitazar, netoglitazone, oxeglitazar, peliglitazar, pemaglitazar, perfluorononanoic acid, pioglitazone, prostaglandin J2, ragaglitazar, reglitazar, rivoglitazone, rosiglitazone, RS5444, saroglitazar, sitoglitazar, soderglitazar, telmisartan, tesaglitazar, and troglitazone. Other suitable PPARγ agonists are described in Masson and Caumont-Bertrand, PPAR Agonist Compounds, Preparation and Uses, U.S. Patent Application Publication No. 2011 / 0195993, which is incorporated by reference in its entirety.

[0063] The therapeutic compound disclosed herein can be PPARδ agonist.The example of suitable PPARδ agonist includes but is not limited to 15-H-eicosatetraenoic acid, 15-hydroperoxy-eicosatetraenoic acid, arachidonic acid, bezafibrate, daidzein, elafibulana, fonadelpar, genistein, GW-0742, GW-501516, L-165,041, ianifibulana, LG-101506, seradelpar, soderglitazar and tetradecylthioacetate.

[0064] The therapeutic compounds disclosed herein may be dual PPAR-α / γ agonists. Examples of suitable dual PPAR-α / γ agonists include, but are not limited to, aleglitazar, muraglitazar, saroglitazar, and tesaglitazar.

[0065] The therapeutic compound disclosed herein may be a PPAR-13 agonist. In another embodiment, the PPAR-13 agonist is, but is not limited to, endurobol and / or GW0742.

[0066] The therapeutic compound disclosed herein can be a cancer drug. Examples of suitable cancer drugs include, but are not limited to, alkylating agents, antimetabolites, plant alkaloids and terpenoids, topoisomerase inhibitors and cytotoxic antibiotics. Alkylating agents include carboplatin, chlorambucil, cisplatin, cyclophosphamide, ifosfamide, oxaliplatin and mechlorethamine. Antimetabolites include azathioprine and mercaptopurine. Plant alkaloids and terpenoids include vinca alkaloids such as vincristine, vinblastine, vinorelbine and vindesine, podophyllotoxins such as etoposide and teniposide, and taxanes such as docetaxel and ortataxel. Topoisomerase inhibitors include type i topoisomerase inhibitors of the camptothecin class, such as exatecan, irinotecan, rutotecan, topotecan, BNP1350, CKD602, DB67 (AR67), and ST1481, and type ii inhibitors of the epipodophyllotoxin class, such as amsacrine, etoposide, etoposide phosphate, and teniposide.Cytotoxic antibiotics include actinomycins, such as actinomycin d, bacitracin, colistin (polymyxin E) and polymyxin b, anthracenediones, such as mitoxantrone and pixantrone, and anthracyclines, such as bleomycin, doxorubicin (adriamycin), daunorubicin (daunomycin), epirubicin, idarubicin, mitomycin, plicamycin, and valrubicin. Repurposed drugs including PARP inhibitors, kinase inhibitors, and anti-rheumatic drugs such as mebendazole, beta-blockers, aminocoumarin antibiotics such as novobiocin, methotrexate and auranofin

[0067] The therapeutic compound disclosed herein can be a sympathomimetic amine. Sympathomimetic amines are a class of therapeutic compounds that mimic the effects of sympathetic nervous system transmitters, such as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), and / or dopamine. Sympathomimetic amines can act as α-adrenergic agonists, β-adrenergic agonists, dopaminergic agonists, monoamine oxidase (MAO) inhibitors, and COMT inhibitors. Such therapeutic compounds are used to treat cardiac arrest, hypotension, or delay premature labor, among others. Examples of suitable sympathomimetic amines include, but are not limited to, clenbuterol, salbutamol, ephedrine, pseudoephedrine, methamphetamine, amphetamine, phenylephrine, isoproterenol, dobutamine, methylphenidate, rizamphetamine, cathine, cathinone, methicinone, cocaine, benzylpiperazine (BZP), methylenedioxypyrovalerone (MDPV), 4-methylaminorex, pemoline, phenmetrazine, and propylhexedrine.α-adrenergic agonists include phenylephrine, propylhexedrine, and pseudoephedrine.β-adrenergic agonists include clenbuterol, dobutamine, ephedrine, isoproterenol, and salbutamol. Dopaminergic / norepinephrine agonists include cocaine (DA / NE reuptake inhibitor), rizamfetamine (5HT / DA / NE reuptake inhibitor), methylphenidate (DA / NE reuptake inhibitor), and methylenedioxypyrovalerone (DA / NE reuptake inhibitor). Neurotransmitter releasing agents include amphetamine (DA / NE releaser), benzylpiperazine (DA / NE releaser), cathine (DA / NE releaser), cathinone (DA / NE releaser), methamphetamine (DA / NE releaser), methicinone (DA / NE releaser), 4-methylaminorex (DA / NE releaser), pemoline, phenmetrazine (DA / NE releaser), and phenethylamine (DA / NE releaser).

[0068] The therapeutic compound disclosed herein can be an inotropic agent.The example of suitable sympathomimetic amine includes but is not limited to aniracetam, cacao, caffeine, choline, choline bitartrate, choline citrate, citicoline, CDP-choline, coluracetam, 5-HTP, melatonin, methiphenidate, modafinil, nefiracetam, nicotine, nuopep, oxiracetam, phenibut, phenylpiracetam, piracetam, pramiracetam and vinpocetine.

[0069] The therapeutic compounds disclosed herein can be CNS agents. Examples of suitable CNS agents include, but are not limited to, amphetamines, anticholinergics, anticonvulsants, anti-dementia drugs, antidepressants, antispasmodics, antiemetics, anti-migraine drugs, anti-obesity drugs, anti-Parkinson drugs, antipsychotics, anti-anxiety drugs, attention deficit hyperactivity disorder drugs, benzodiazepines, bipolar drugs, calcitonin gene-related peptide (CGRP) receptor antagonists, calcium channel modifiers, cholinesterase inhibitors, dopamine agonists, dopamine precursors and / or l-amino acid decarboxylase inhibitors, anti-emetics, anti-emetics, anti-inflammatory drugs ... These include therapeutic adjuvants, ergot alkaloids, fibromyalgia drugs, gamma-aminobutyric acid (GABA) enhancers, monoamine oxidase inhibitors, monoamine oxidase B inhibitors, multiple sclerosis drugs, N-methyl-D-aspartate (NMDA) receptor antagonists, selective serotonin reuptake inhibitors / serotonin and norepinephrine reuptake inhibitors (SSRI / SNRI), serotonin (5-HT) receptor agonists, sleep disorder drugs, sleep promoters, sodium channel modifiers, tricyclics, and wake promoters. Other CNS therapeutic compounds include, but are not limited to, amifampridine, deutetrabenazine, dextromethorphan, edaravone, quinidine, riluzole, tetrabenazine, and valbenazine.

[0070] Anticonvulsants include, but are not limited to, brivaracetam, cannabidiol, cenobamate, divalproex, ethosuximide, felbamate, fenfluramine, lamotrigine, levetiracetam, methoxyimide perampanel, topiramate and valproic acid.Antidepressants include, but are not limited to, amitriptyline, aripiprazole, bupropion, chlordiazepoxide, esketamine, fluoxetine, isocarboxazid, ketamine, maprotiline, mirtazapine, olanzapine, perphenazine, phenelzine sulfate, quetiapine fumarate, selegiline and tranylcypromine sulfate.Antidementals include, but are not limited to, donepezil, ergoloids, galantamine, memantine, rivastigmine and rivastigmine. Antiemetics include, but are not limited to, aprepitant, amisulpride, chlorpromazine, diphenhydramine, doxylamine, dronabinol, fosnetopitant, granisetron, hydroxyzine, meclizine, metoclopramide, nabilone, netopitant, ondansetron, ondansetron, palonosetron, perphenazine, prochlorperazine edisylate, prochlorperazine, promethazine, pyridoxine, rolapitant, scopolamine, and trimethobenzamide. Antimigraine drugs include, but are not limited to, caffeine, dihydroergotamine, divalproex, ergotamine, propranolol, timolol, topiramate, and valproic acid. Anti-obesity agents include, but are not limited to, benzphetamine, bupropion, diethylpropion, liraglutide, methamphetamine, naltrexone, phendimetrazine, phentermine and topiramate. Anti-Parkinson's agents include, but are not limited to, amantadine, benztropine, carbidopa, diphenhydramine, entacapone, istradefylline, levodopa, opicapone, trihexyphenidyl and tolcapone.Antipsychotics include, but are not limited to, aripiprazole, asenapine, brexiprazole, cariprazine, chlorpromazine, clozapine, fluphenazine, fluphenazine, haloperidol, iloperidone, loxapine, lurasidone, olanzapine, paliperidone, perphenazine, pimavanserin, pimozide, prochlorperazine, quetiapine, risperidone, thioridazine, thiothixene, trifluoroperazine, and ziprasidone. Antispasmodics include, but are not limited to, baclofen, dantrolene, and tizanidine. Antianxiety drugs include, but are not limited to, buspirone, doxepin, duloxetine, escitalopram, meprobamate, paroxetine, sertraline, and venlafaxine hydroxyzine. Attention deficit hyperactivity disorder drugs include, but are not limited to, atomoxetine, clonidine, dexmethylphenidate, dextroamphetamine, guafacine, methylphenidate, lizamfetamine, and methamphetamine.Bipolar drugs include, but are not limited to, aripiprazole, asenapine, carbamazepine, divalproex, lamotrigine, lithium, lurasidone, olanzapine, quetiapine, risperidone, valproic acid, and ziprasidone.Benzodiazepines include, but are not limited to, alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, and oxazepam.CGRP receptor antagonists include, but are not limited to, eptinezumab, erenumab, fremanezumab, galcanezumab, rimegepant, and ubrogepant. Dopamine agonists include, but are not limited to, apomorphine, bromocriptine, pramipexole Di, ropinirole and rotigotine.Dopamine precursor and / or L-amino acid decarboxylase inhibitors include, but are not limited to, carbidopa, carbidopa and levodopa.Fibromyalgia drugs include, but are not limited to, duloxetine, milnacipran and pregabalin.GABA enhancers include, but are not limited to, clobazam, clonazepam, clorazepate, diazepam, gabapentin, lorazepam, pregabalin, phenobarbital, primidone, tiagabine, and vigabatrin. Monoamine oxidase B inhibitors include, but are not limited to, rasagiline, safinamide, and selegiline. Multiple sclerosis agents include, but are not limited to, alemtuzumab, cladribine, dalfampridine, dimethyl fumarate, diroximel fumarate, fingolimod, glatiramer, interferon beta-1a, interferon beta-1b, mitoxantrone, monomethyl fumarate, natalizumab, ocrelizumab, ozanimod, peginterferon beta-1a, siponimod, and teriflunomide. NMDA receptor antagonists include, but are not limited to, memantine. Serotonin (5-HT) receptor agonists include, but are not limited to, almotriptan, eletriptan, frovatriptan, lasmiditan, naratriptan, naproxen, rizatriptan benzoate, sumatriptan, sumatriptan, and zolmitriptan. Sodium channel agents include, but are not limited to, carbamazepine, eslicabazepine, ethotoin, fosphenytoin, lactosamide, oxcarbazepine, phenytoin, phenytoin, rufinamide, and zonisamide. SSRI / SNRI include, but are not limited to, citalopram, desvenlafaxine, duloxetine, escitalopram oxalate, fluoxetine, fluvoxamine, levomilnacipran, nefazodone, paroxetine, sertraline, trazodone, venlafaxine, vilazodone, and vortioxetine. Sleep promoters include, but are not limited to, doxepin, estazolam, eszopiclone, flurazepam, lemborexant, quazepam, ramelteon, suvorexant, tasimelteon, temazepam, triazolam, zaleplon, zopiclone, and zolpidem. Wake promoters include, but are not limited to, armodafinil, modafanil, calcium / magnesium / potassium / sodium oxybate, pitolisant, and sorianfetol.Tricyclic agents include, but are not limited to, amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, imipramine pamoate, nortriptyline, protriptyline, and trimipramine.

[0071] The therapeutic compounds disclosed herein can be antihyperlipidemic agents. There are several classes of antihyperlipidemic agents (also known as hypolipidemic agents). They can differ in both their impact on cholesterol profile and adverse effects. For example, some lower low-density lipoprotein (LDL), while others preferentially increase high-density lipoprotein (HDL). Clinically, the choice of agent depends on the individual's cholesterol profile, the individual's cardiovascular risk, and / or the individual's liver and kidney function. Examples of suitable antihyperlipidemic agents include, but are not limited to, fibrates, statins, tocotrienols, niacin, bile acid sequestrants (resins), cholesterol absorption inhibitors, pancreatic lipase inhibitors, and sympathomimetic amines.

[0072] The therapeutic compound disclosed herein can be fibrate.Fibrates are a class of amphiphilic carboxylic acids that have lipid level modification properties.These therapeutic compounds are used for various metabolic disorders.One non-limiting use is as an antihyperlipidemic drug, which can reduce the level of triglycerides and LDL, and increase the level of HDL.Suitable examples of fibrates include, but are not limited to, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibrate acid, gemfibrozil, nafenopin, lonifibrate and simfibrate.

[0073] The therapeutic compound disclosed herein can be a statin.Statins (or HMG-CoA reductase inhibitors) are a class of therapeutic compounds that are used to lower LDL and / or cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver.To compensate for the decrease in cholesterol availability, the synthesis of LDL receptors in the liver increases, and the clearance of LDL particles from the blood increases.Examples of suitable statins include, but are not limited to, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin.

[0074] The therapeutic compound disclosed herein can be tocotrienol.Tocotrienol is another class of HMG-CoA reductase inhibitor, and can be used to lower LDL and / or cholesterol levels by inducing hepatic LDL receptor upregulation and / or lowering plasma LDL levels.Suitable examples of tocotrienol include, but are not limited to, γ-tocotrienol and δ-tocotrienol.

[0075] The therapeutic compound disclosed herein can be niacin. Niacin is a class of therapeutic compounds that have lipid level modifying properties. For example, niacin can lower LDL by selectively inhibiting hepatic diacylglycerol acyltransferase 2, and reduce the synthesis of triglycerides and secretion of VLDL via receptors HM74 and HM74A or GPR109A. These therapeutic compounds are used for various metabolic disorders. One non-limiting use is as an antihyperlipidemic drug that can inhibit the breakdown of fat in adipose tissue. Because niacin blocks the breakdown of fat, it causes a decrease in free fatty acids in the blood, resulting in a decrease in the secretion of very low density lipoprotein (VLDL) and cholesterol by the liver. By lowering VLDL levels, niacin can also increase HDL levels in the blood. Examples of suitable niacin include, but are not limited to, acipimox, niacin, nicotinamide, and vitamin B3.

[0076] The therapeutic compound disclosed herein can be a bile acid sequestrant. Bile acid sequestrants (also known as resins) are a class of therapeutic compounds used to bind to certain components of bile in the digestive tract. They disrupt the enterohepatic circulation of bile acids by capturing bile acids and preventing their reabsorption from the intestine. Bile acid sequestrants are particularly effective in lowering LDL and cholesterol by capturing cholesterol-containing bile acids released in the intestine and preventing their reabsorption from the intestine. In addition, bile acid sequestrants can also increase HDL levels. Examples of suitable bile acid sequestrants include, but are not limited to, cholestyramine, colesevelam, and colestipol.

[0077] The therapeutic compound disclosed herein can be a cholesterol absorption inhibitor.Cholesterol absorption inhibitor is a class of therapeutic compounds that inhibits cholesterol absorption from the intestine.Reduction of cholesterol absorption leads to upregulation of LDL receptors on cell surface and increased LDL cholesterol uptake into these cells, thus reducing LDL levels in plasma.Examples of suitable cholesterol absorption inhibitors include, but are not limited to, ezetimibe, phytosterols, sterols and stanols.

[0078] The therapeutic compound disclosed herein can be a fat absorption inhibitor.Fat absorption inhibitors are a class of therapeutic compounds that inhibit the absorption of fat from the intestine.Reducing fat absorption reduces calorie intake.In one aspect, fat absorption inhibitors inhibit pancreatic lipase, an enzyme that breaks down triglycerides in the intestine.Examples of suitable fat absorption inhibitors include, but are not limited to, orlistat.

[0079] The therapeutic compound disclosed herein can be an anthelmintic. An anthelmintic (also known as an antihelmintic, antihelminthic agent or helminthic) is a group of anthelmintic drugs that stun or kill parasites (helminths) and other internal parasites, thereby expelling them from the body without causing significant damage to the host. They can also be called vermicide (stunning) or vermicide (killing). Non-limiting examples of anthelmintic drugs include aminoacetonitrile derivatives, artemisinin, avermectin, benzimidazole, milbemycin, octadepsipeptide, spiroindole, diethylcarbamazine, levamisole, monepantel, niclosamide, nitazoxanide, metrifonate, praziquantel, pyrantel pamoate, salicylanilide, suramin, or any combination thereof. In aspects of this embodiment, artemisinins include, but are not limited to, arteline acid, artemether, artemotil (β-arteether), artenimol, artemoran, artesunate, dihydroartemisinin, butyric acid ester of dihydroartemisinin, or any combination thereof. In aspects of this embodiment, avermectins include, but are not limited to, abamectin, doramectin, emamectin, ivermectin, selamectin, or any combination thereof. In aspects of this embodiment, benzimidazoles include, but are not limited to, albendazole, cyclobendazole, fenbendazole, flubendazole, mebendazole, thiabendazole, triclabendazole, or any combination thereof. In aspects of this embodiment, milbemycins include, but are not limited to, moxidectin, milbemycin oxime, or any combination thereof. In aspects of this embodiment, octadepsipeptides include, but are not limited to, emodepsides. In an aspect of this embodiment, spiroindoles include, but are not limited to, decanthel.

[0080] The therapeutic compound disclosed herein can be retinoid.Retinoid is a class of chemical compounds that is vitamin A or chemically related to vitamin A.Non-limiting examples of retinoid include first-generation retinoids such as alitretinoin, isotretinoin retinol, retinal, and tretinoin (retinoic acid); second-generation retinoids such as etretinate and its metabolite acitretin; third-generation retinoids such as adapalene, bexarotene, and tazarotene; and fourth-generation retinoids such as trifarotene.

[0081] The therapeutic compound disclosed herein can be a vitamin. Non-limiting examples of retinoids include vitamin A, vitamin D, vitamin E, and vitamin K. Vitamin A includes, but is not limited to, α-carotene, β-carotene, retinol, and tretinoin. Vitamin D includes vitamin D, such as ergosterol and ergocalciferol. 2 , 7-dehydrocholesterol, previtamin D 3 Vitamin D, such as cholecalciferol, 25-hydroxycholecalciferol, calcitriol (1,2,5 dihydroxycholecalciferol), and calcitronic acid 3 , dihydroergocalciferol, and other vitamin D 4 , Vitamin D 5 Vitamin D analogs, such as, but not limited to, alphacalcidol, dihydrotachysterol, calcipotriol, tacalcitol, and paricalcitol. Vitamin E, such as, but not limited to, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, and tocophersolan. Vitamin K, such as, but not limited to, vitamin K quinones, naphthoquinones, phylloquinones, 1 , Vitamin K such as menaquinone 2 , Vitamin K such as Menadione 3 , Vitamin K 4, Vitamin K such as 4-amino-2-methyl-1-naphthol 5 , Vitamin K such as 2-methylnaphthalene-1,4-diamine 6 , Vitamin K such as 4-amino-3-methyl-1-naphthol 7 Examples include:

[0082] The therapeutic compound disclosed herein can be a cannabinoid. Examples of suitable cannabinoid drugs include, but are not limited to, phytocannabinoids, endocannabinoids, and synthetic cannabinoids. Phytocannabinoids include tetrahydrocannabinol (e.g., delta-9-tetrahydrocannabinol (Δ9-THC, THC) and delta-8-tetrahydrocannabinol (Δ8-THC), etc.), cannabidiol, cannabinol, cannabigerol, tetrahydrocannabivarin, cannabidivarin, and cannabichromene. Endocannabinoids include arachidonoylethanolamine (anandamide or AEA), 2-arachidonoylglycerol (2-AG), 2-arachidonylglyceryl ether (noladin ether), N-arachidonoyldopamine (NADA), virodamine (OAE) and lysophosphatidylinositol (LPI). Synthetic cannabinoids include dronabinol (Marinol), nabilone (Cesamet), Sativex, rimonabant (SR141716), JWH-018, JWH-073, CP-55940, dimethylheptylpyran, HU-210, HU-331, SR144528, WIN55,212-2, JWH-133, levonantradol (Nantrodolum), and AM-2201.

[0083] The therapeutic compound disclosed herein can be a cannabinoid receptor modulator.Cannabinoid receptor modulators include but are not limited to CB1 agonist, CB1 antagonist, CB2 agonist, CB2 antagonist, GPR18 (NAGly) agonist, GPR18 (NAGly) antagonist, GPR55 agonist, GPR55 antagonist, GPR119 agonist, GPR119 antagonist, eCBT inhibitor, FAAH activator, FAAH inhibitor, MAGL inhibitor, ABHD6 inhibitor, ABHD6 inhibitor and ABHD12 inhibitor.

[0084] The therapeutic compound disclosed herein can be an antiemetic.Non-limiting examples of antiemetic include 5-HT3 serotonin ion channel antagonist, 5-HT serotonin G protein receptor antagonist, CB1 agonist, D2 / D3 antagonist, H1 antagonist, mACh antagonist, NK1 antagonist, cerium oxalate, dexamethasone, lorazepam, midazolam and propofol.5-HT3 serotonin ion channel antagonist includes but is not limited to alosetron, azasetron, bemesetron, cilansetron, clozapine, dazopride, dolasetron, granisetron, lerisetron, metoclopramide, mianserin, mirtazapine, olanzapine, ondansetron, palonosetron, quetiapine, ramosetron, licasetron, tropisetron and zatosetron. 5-HT serotonin G protein receptor antagonists include, but are not limited to, clozapine, cyproheptadine, hydroxyzine, olanzapine, risperidone and ziprasidone.CB1 agonists (or cannabinoids) include, but are not limited to, dronabinol, nabilone, tetrahydrocannabinol (cannabis).D2 / D3 antagonists include, but are not limited to, alizapride, bromopride, chlorpromazine, clebopride, domperidone, haloperidol, hydroxyzine itopride, metoclopramide, metopimazine, prochlorperazine, thiethylperazine and trimethobenzamide.H1 antagonists (antihistamines) include, but are not limited to, cyclizine, dimenhydrinate, diphenhydramine, hydroxyzine, meclizine and promethazine. mACh antagonists (anticholinergics) include, but are not limited to, atropine, diphenhydramine, hydroxyzine, hyoscyamine, and scopolamine.NK1 antagonists include, but are not limited to, aprepitant, casopitant, ezopitant, fosaprepitant, maropitant, netupitant, rolapitant, and vestipitant.

[0085] The therapeutic compounds disclosed herein can be those shown in Table 1. [Table 1] TIFF2024511208000002.tif225162TIFF2024511208000003.tif134162

[0086] In one embodiment, a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in an amount, e.g., about 0.05%, about 0.1%, about 1%, about 2.5%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 22.5%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50% (by weight). In one embodiment, a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in an amount, e.g., at least 0.05%, at least 0.1%, at least 1%, at least 2.5%, at least 5%, at least 7.5%, at least 10%, at least 12.5%, at least 15%, at least 17.5%, at least 20%, at least 22.5%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% (by weight). In one embodiment, a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in an amount, e.g., up to 0.05%, up to 0.1%, up to 1%, up to 2.5%, up to 5%, up to 7.5%, up to 10%, up to 12.5%, up to 15%, up to 17.5%, up to 20%, up to 22.5%, up to 25%, up to 30%, up to 35%, up to 40%, up to 45%, or up to 50% (by weight).

[0087] In one embodiment, the pharmaceutical composition disclosed herein may be administered in a concentration of, for example, about 0.05% to about 1%, about 0.05% to about 2.5%, about 0.05% to about 5%, about 0.05% to about 7.5%, about 0.05% to about 10%, about 0.05% to about 12.5%, about 0.05% to about 15%, about 0.05% to about 17.5%, about 0.05% to about 20%, about 0.05% to about 22.5%, about 0.05% to about 25%, about 0.05% to about 30%, about 0.05% to about 40%, about 0.05% to about 50%, about 0.1% to about 1%, about 0.1% to about 2.5%, about 0.1% to about ... about 7.5%, about 0.1% to about 10%, about 0.1% to about 12.5%, about 0.1% to about 15%, about 0.1% to about 17.5%, about 0.1% to about 20%, about 0.1% to about 22.5%, about 0.1% to about 25%, about 0.1% to about 30%, about 0.1% to about 40%, about 0.1% to about 50%, about 1% to about 2.5%, about 1% to about 5%, about 1% to about 7.5%, about 1% to about 10%, about 1% to about 12.5%, about 1% to about 15%, about 1% to about 17.5%, about 1% to about 20%, about 1% to about 22.5%, about 1% to about 25%, about 1% to about 30%, about 1% to about 40%, about 1% to About 50%, about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5% to about 90%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 90%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 30% about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 90%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 90%, about 60% to about 70%, about 60% to about 80%, about 60% to about 90%, about 70% to about 80%, about 70% to about 90%, or about 80% to about 90% (by weight) of one or more therapeutic compounds disclosed herein.

[0088] In one embodiment, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about 40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 60 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL, about 100 mg / mL, about 125 mg / mL, about 150 mg / mL, about 175 mg / mL, about 200 mg / mL, about 225 mg / mL, about 250 mg / mL, about 260 mg / mL, about 275 mg / mL, about 280 mg / mL, about 290 mg / mL, about 300 mg / mL, about 310 mg / mL, about 325 mg / mL, about 330 mg / mL, about 340 mg / mL, about 350 mg / mL, about 360 mg / mL, about 370 mg / mL, about 380 mg / mL, about 390 mg / mL, about 400 mg / mL, about 410 mg / mL, about 425 mg / mL, about 430 mg / mL, about 440 mg / mL, about 450 mg / mL, about 460 mg / mL, about 470 mg / mL, about 480 mg / mL, about 490 mg / mL, about 500 mg / mL, about 510 mg / mL, about 520 mg / mL, about 530 mg / mL, about 540 mg / mL, about 550 mg / mL, about 560 mg / mL, about 570 mg / mL, about 580 mg / mL, about 590 mg / mL, about 600 mg / mL, about 650 mg / mL, about 70 mg / mL, about 75 mg / mL, about 100 mg / mL mL, about 250 mg / mL, about 275 mg / mL, about 300 mg / mL, about 325 mg / mL, about 350 mg / mL, about 375 mg / mL, about 400 mg / mL, about 425 mg / mL, about 450 mg / mL, about 475 mg / mL, about 500 mg / mL, about 525 mg / mL, about 550 mg / mL, about 575 mg / mL, or about 600 mg / mL. In one embodiment, the pharmaceutical compositions disclosed herein have a cytotoxicity of at least 25 mg / mL, at least 30 mg / mL, at least 35 mg / mL, at least 40 mg / mL, at least 45 mg / mL, at least 50 mg / mL, at least 60 mg / mL, at least 65 mg / mL, at least 70 mg / mL, at least 75 mg / mL, at least 100 mg / mL, at least 125 mg / mL, at least 150 mg / mL, at least 175 mg / mL, at least 200 mg / mL, at least 225 mg / mL, at least 250 mg / mL, at least 260 mg / mL, at least 275 mg / mL, at least 280 mg / mL, at least 300 mg / mL, at least 350 mg / mL, at least 40 mg / mL, at least 45 mg / mL, at least 50 mg / mL, at least 60 mg / mL, at least 65 mg / mL, at least 70 mg / mL, at least 75 mg / mL, at least 100 mg / mL, at least 125 mg / mL, at least 150 mg / mL, at least 175 mg / mL, at least 200 mg / mL, at least 225 mg / mL, at least 300 mg / mL, at least 350 mg / mL, at least 400 mg / mL, at least 450 mg / mL, at least 500 mg / mL, at least 600 mg / mL, at least 650 mg / mL, at least 70 mg / mL, at least 75 mg / mL, at least 100 mg / mL, at least 125 mg / mL, at least 150 mg / mL, at least 175 mg / mL, at least 200 mg / mL, at least 225 mg / mL, at least 350 mg / mL, at least The therapeutic compound may comprise one or more therapeutic compounds in a concentration of at least 250 mg / mL, at least 275 mg / mL, at least 300 mg / mL, at least 325 mg / mL, at least 350 mg / mL, at least 375 mg / mL, at least 400 mg / mL, at least 425 mg / mL, at least 450 mg / mL, at least 475 mg / mL, at least 500 mg / mL, at least 525 mg / mL, at least 550 mg / mL, at least 575 mg / mL, or at least 600 mg / mL.In one embodiment, the pharmaceutical compositions disclosed herein may be administered in a concentration of up to 25 mg / mL, up to 30 mg / mL, up to 35 mg / mL, up to 40 mg / mL, up to 45 mg / mL, up to 50 mg / mL, up to 60 mg / mL, up to 65 mg / mL, up to 70 mg / mL, up to 75 mg / mL, up to 100 mg / mL, up to 125 mg / mL, up to 150 mg / mL, up to 175 mg / mL, up to 200 mg / mL, up to 225 mg / mL, for example. g / mL, up to 250 mg / mL, up to 275 mg / mL, up to 300 mg / mL, up to 325 mg / mL, up to 350 mg / mL, up to 375 mg / mL, up to 400 mg / mL, up to 425 mg / mL, up to 450 mg / mL, up to 475 mg / mL, up to 500 mg / mL, up to 525 mg / mL, up to 550 mg / mL, up to 575 mg / mL, or up to 600 mg / mL.

[0089] In one embodiment, the pharmaceutical composition disclosed herein may be, for example, about 25 mg / mL to about 50 mg / mL, about 25 mg / mL to about 75 mg / mL, about 25 mg / mL to about 100 mg / mL, about 25 mg / mL to about 125 mg / mL, about 25 mg / mL to about 150 mg / mL, about 25 mg / mL to about 200 mg / mL, about 25 mg / mL to about 250 mg / mL, about 25 mg / mL to about 300 mg / mL, about 25 mg / mL to about 350 mg / mL, about 25 mg / mL to about 400 mg / mL, about 25 mg / mL to about 450 mg / mL, about 25 mg / mL to about 5 00mg / mL, about 25mg / mL to about 550mg / mL, about 25mg / mL to about 600mg / mL, about 50mg / mL to about 100mg / mL, about 50mg / mL to about 150mg / mL, about 50mg / mL to about 200mg / mL, about 50mg / mL to about 250mg / mL, about 5 0mg / mL~about 300mg / mL, about 50mg / mL~about 350mg / mL, about 50mg / mL~about 400mg / mL, about 50mg / mL~about 450mg / mL, about 50mg / mL~about 500mg / mL, about 50mg / mL~about 550mg / mL, about 50mg / mL~about 60 0mg / mL, about 75mg / mL to about 100mg / mL, about 75mg / mL to about 150mg / mL, about 75mg / mL to about 200mg / mL, about 75mg / mL to about 250mg / mL, about 75mg / mL to about 300mg / mL, about 75mg / mL to about 350mg / mL, about 75 mg / mL~about 400mg / mL, about 75mg / mL~about 450mg / mL, about 75mg / mL~about 500mg / mL, about 75mg / mL~about 550mg / mL, about 75mg / mL~about 600mg / mL, about 100mg / mL~about 150mg / mL, about 100mg / mL~about 2 00mg / mL, about 100mg / mL to about 250mg / mL, about 100mg / mL to about 300mg / mL, about 100mg / mL to about 350mg / mL, about 100mg / mL to about 400mg / mL, about 100mg / mL to about 450mg / mL, about 100mg / mL to about 500mg / mL, about 100mg / mL to about 550mg / mL, about 100mg / mL to about 600mg / mL, about 150mg / mL to about 200mg / mL, about 150mg / mL to about 250mg / mL, about 150mg / mL to about 300mg / mL, about 150mg / mL to about 350mg / mL,Approximately 150mg / mL to approximately 400mg / mL, approximately 150mg / mL to approximately 450mg / mL, approximately 150mg / mL to approximately 500mg / mL, approximately 150mg / mL to approximately 550mg / mL, approximately 150mg / mL to approximately 600mg / mL, approximately 200m g / mL~about 250mg / mL, about 200mg / mL~about 300mg / mL, about 200mg / mL~about 350mg / mL, about 200mg / mL~about 400mg / mL, about 200mg / mL~about 450mg / mL, about 200mg / mL~ Approx. 500mg / mL, Approx. 200mg / mL~Approx. 550mg / mL, Approx. 200mg / mL~Approx. 600mg / mL, Approx. 250mg / mL~Approx. 300mg / mL, Approx. 250mg / mL~Approx. 350mg / mL, Approx. 250mg / mL~Approx. 400m g / mL, about 250 mg / mL to about 450 mg / mL, about 250 mg / mL to about 500 mg / mL, about 250 mg / mL to about 550 mg / mL, about 250 mg / mL to about 600 mg / mL, about 300 mg / mL to about 350 mg / mL, Approximately 300mg / mL to approximately 400mg / mL, approximately 300mg / mL to approximately 450mg / mL, approximately 300mg / mL to approximately 500mg / mL, approximately 300mg / mL to approximately 550mg / mL, approximately 300mg / mL to approximately 600mg / mL, approximately 350m g / mL~about 400mg / mL, about 350mg / mL~about 450mg / mL, about 350mg / mL~about 500mg / mL, about 350mg / mL~about 550mg / mL, about 350mg / mL~about 600mg / mL, about 400mg / mL~ The compositions include one or more therapeutic compounds at a concentration of about 450 mg / mL, about 400 mg / mL to about 500 mg / mL, about 400 mg / mL to about 550 mg / mL, about 400 mg / mL to about 600 mg / mL, about 450 mg / mL to about 500 mg / mL, about 450 mg / mL to about 550 mg / mL, about 450 mg / mL to about 600 mg / mL, about 500 mg / mL to about 550 mg / mL, about 500 mg / mL to about 600 mg / mL, and about 550 mg / mL to about 600 mg / mL.

[0090] Glycerolipids The pharmaceutical compositions disclosed herein may include one or more glycerolipids. Glycerolipids are hydrophobic molecules that are mainly composed of mono-, di- and tri-substituted glycerols and have an HLB of less than 4. One group of glycerolipids is glycerides, in which one, two or all three hydroxyl groups of glycerol are esterified with fatty acids to produce monoglycerides, diglycerides, and triglycerides, respectively. In these compounds, each hydroxyl group of glycerol may be esterified with the same or different fatty acids. In some embodiments, the monoglycerides disclosed herein are C 12 -C 24 In some embodiments, the diglycerides disclosed herein may include saturated or unsaturated fatty acids having a carbon length of C 12 -C 24 or C 12 -C 24 In some embodiments, the triglycerides disclosed herein may comprise two saturated or unsaturated fatty acids having a carbon length of C 12 -C 24 one saturated or unsaturated fatty acid with a carbon length of C 12 -C 24 Two saturated or unsaturated fatty acids with a carbon length of 0.01 to 0.01, respectively. 12 -C 24 The fatty acid may contain three saturated or unsaturated fatty acids having a carbon length of 1.

[0091] Two types of glycerolipids are used in formulating one or more therapeutic compounds disclosed herein to produce the pharmaceutical compositions disclosed herein. One type is hard fat, i.e., glycerolipids that are solid at 18°C. The disclosed hard fats or glycerolipids that are solid at 18°C ​​have several purposes. During the formulation process of the pharmaceutical compositions disclosed herein, the hard fats form complexes with the therapeutic compounds disclosed herein and stabilize them in the glycerolipid matrix, which prevents the compounds from precipitating. Furthermore, during administration of the pharmaceutical compositions disclosed herein, the hard fats disclosed herein induce lipid digestion processes to stimulate the release of bile from the gallbladder and enhance emulsification of the administered pharmaceutical composition. Furthermore, the hard fats present in the pharmaceutical composition serve as substrates for pancreatic lipases, which break down these hard fats into glycerol and free fatty acids. The presence of these digested lipid molecules, along with the associated therapeutic compounds, induces their absorption by the enterocytes lining the lumen of the duodenum of the small intestine. Once internalized, enterocytes then process and distribute the free fatty acid / therapeutic compound mixture to the lymphatic system. The disclosed hard fats or glycerolipids that are solid at 18°C ​​do not have emulsion-forming properties because these lipids do not exhibit a critical micelle concentration. Therefore, another purpose of the disclosed hard fats or glycerolipids that are solid at 18°C ​​is to prevent formulation ingredients that have a critical micelle concentration from initiating emulsification by diluting these ingredients below their critical micelle concentration and providing an anhydrous environment that reduces the necessary interaction of these ingredients to initiate emulsification.

[0092] Another type of glycerolipid used in formulating one or more therapeutic compounds disclosed herein is a liquid fat or liquid oil, i.e., a glycerolipid that is liquid at 18°C. The main purpose of the disclosed liquid fat or glycerolipid that is liquid at 18°C ​​is as a solvent that promotes the dissolution of the therapeutic compounds disclosed herein, as well as a stabilizer that prevents the disclosed therapeutic compounds from precipitating from the glycerolipid matrix. The disclosed liquid fat or glycerolipid that is liquid at 18°C ​​does not have emulsion-forming properties, since these lipids do not exhibit a critical micelle concentration. Therefore, another purpose of the disclosed liquid fat or glycerolipid that is liquid at 18°C ​​is to prevent formulation components that have a critical micelle concentration from starting to emulsify by diluting these components below their critical micelle concentration and providing an anhydrous environment that reduces the necessary interaction of these components to start emulsification.

[0093] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more glycerolipids in an amount of, for example, about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), about 75% (by weight), about 80% (by weight), about 85% (by weight), about 90% (by weight), or about 95% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more glycerolipids in an amount of, for example, at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), at least 80% (by weight), at least 85% (by weight), at least 90% (by weight), or at least 95% (by weight). In some embodiments, pharmaceutical compositions disclosed herein may comprise one or more glycerolipids in an amount, for example, of up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), up to 80% (by weight), up to 85% (by weight), up to 90% (by weight), up to 95% (by weight), or up to 99% (by weight).

[0094] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 25% to about 30%, about 25% to about 40%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 70%, about 25% to about 80%, about 25% to about 90%, about 30% to about 40%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about About 70%, about 30% to about 80%, about 30% to about 90%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 40% to about 75%, about 40% to about 80%, about 40% to about 85%, about 40% to about 90%, about 40% to about 95%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 45% to about 75%, about 45% to about 80%, about 45% to about 85%, about 45% to about 90%, about 45% to about 95%, about 50% to about 55%, about 50% to about 60%, about 50% ~ about 65%, about 50% to about 70%, about 50% to about 75%, about 50% to about 80%, about 50% to about 85%, about 50% to about 90%, about 50% to about 95%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 55% to about 75%, about 55% to about 80%, about 55% to about 85%, about 55% to about 90%, about 55% to about 95%, about 60% to about 65%, about 60% to about 70%, about 60% to about 75%, about 60% to about 80%, about 60% to about 85%, about 60% to about 90%, about 60% to about 95%, about 65% to about 70%, about 65% to about 75%, about 65 The composition may contain one or more glycerolipids in an amount of about 80%, about 65% to about 85%, about 65% to about 90%, about 65% to about 95%, about 70% to about 75%, about 70% to about 80%, about 70% to about 85%, about 70% to about 90%, about 70% to about 95%, about 75% to about 80%, about 75% to about 85%, about 75% to about 90%, about 75% to about 95%, about 80% to about 85%, about 80% to about 90%, about 80% to about 95%, about 80% to about 99%, about 85% to about 90%, about 85% to about 95%, about 85% to about 99%, about 90% to about 95%, or about 90% to about 99%.

[0095] In some embodiments, the pharmaceutical compositions disclosed herein are solid at 18° C., i.e., saturated C 10 -C 18 Mixture of triglycerides, saturated C 10 -C 20 Mixture of triglycerides, saturated C 10 -C 22 Mixture of triglycerides, saturated C 10 -C 24 Mixture of triglycerides, saturated C 12 -C 18 Mixture of triglycerides, saturated C 12 -C 20 Mixture of triglycerides, saturated C 12 -C 22 Mixture of triglycerides, saturated C 12 -C 24 Mixture of triglycerides, saturated C 14 -C 18 Mixture of triglycerides, saturated C 14 -C 20 Mixture of triglycerides, saturated C 14 -C 22 Mixture of triglycerides, saturated C 14 -C 24 Mixture of triglycerides, saturated C 16 -C 18 Mixture of triglycerides, saturated C 16 -C 20 Mixture of triglycerides, saturated C 16 -C 22 Mixture of triglycerides, saturated C 16 -C 24 Mixture of triglycerides, saturated C 18 -C 20 Mixture of triglycerides, saturated C 18 -C 22 Mixture of triglycerides, saturated C 18 -C 24 Mixture of triglycerides, saturated C 20 -C 22 Mixture of triglycerides, or saturated C 22 -C 24 It may comprise one or more hard fats or glycerolipids comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0096] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated C 10 -C 18 Mixture of triglycerides, unsaturated C 10 -C 20 Mixture of triglycerides, unsaturated C 10 -C 22 Mixture of triglycerides, unsaturated C 10 -C 24 Mixture of triglycerides, unsaturated C 12 -C 18 Mixture of triglycerides, unsaturated C 12 -C 20 Mixture of triglycerides, unsaturated C 12 -C 22 Mixture of triglycerides, unsaturated C 12 -C 24 Mixture of triglycerides, unsaturated C 14 -C 18 Mixture of triglycerides, unsaturated C 14 -C 20 Mixture of triglycerides, unsaturated C 14 -C 22 Mixture of triglycerides, unsaturated C 14 -C 24 Mixture of triglycerides, unsaturated C 16 -C 18 Mixture of triglycerides, unsaturated C 16 -C 20 Mixture of triglycerides, unsaturated C 16 -C 22 Mixture of triglycerides, unsaturated C 16 -C 24 Mixture of triglycerides, unsaturated C 18 -C 20 Mixture of triglycerides, unsaturated C 18 -C 22 Mixture of triglycerides, unsaturated C 18 -C 24 Mixture of triglycerides, unsaturated C 20 -C 22 Mixture of triglycerides, or unsaturated C 22 -C 24It may comprise one or more hard fats or glycerolipids comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0097] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated C 10 -C 18 Mixture of triglycerides, saturated and unsaturated C 10 -C 20 Mixture of triglycerides, saturated and unsaturated C 10 -C 22 Mixture of triglycerides, saturated and unsaturated C 10 -C 24 Mixture of triglycerides, saturated and unsaturated C 12 -C 18 Mixture of triglycerides, saturated and unsaturated C 12 -C 20 Mixture of triglycerides, saturated and unsaturated C 12 -C 22 Mixture of triglycerides, saturated and unsaturated C 12 -C 24 Mixture of triglycerides, saturated and unsaturated C 14 -C 18 Mixture of triglycerides, saturated and unsaturated C 14 -C 20 Mixture of triglycerides, saturated and unsaturated C 14 -C 22 Mixture of triglycerides, saturated and unsaturated C 14 -C 24 Mixture of triglycerides, saturated and unsaturated C 16 -C 18 Mixture of triglycerides, saturated and unsaturated C 16 -C 20 Mixture of triglycerides, saturated and unsaturated C 16 -C 22 Mixture of triglycerides, saturated and unsaturated C 16 -C 24 Mixture of triglycerides, saturated and unsaturated C 18 -C 20 Mixture of triglycerides, saturated and unsaturated C 18 -C22 Mixture of triglycerides, saturated and unsaturated C 18 -C 24 Mixture of triglycerides, saturated and unsaturated C 20 -C 22 A mixture of triglycerides, or saturated and unsaturated C 22 -C 24 It may comprise one or more hard fats or glycerolipids comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0098] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that comprise, consist essentially of, or consist of a mixture of triglycerides that are solid at 18°C, e.g., have a melting point of about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, about 30°C, about 31°C, about 32°C, about 33°C, about 34°C, about 35°C, about 36°C, about 37°C, about 38°C, about 39°C, about 40°C, about 41°C, about 43°C, about 43°C, about 44°C, about 45°C, about 45°C, about 47°C, about 48°C, about 49°C, or about 50°C. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that comprise, consist essentially of, or consist of a mixture of triglycerides that are solid at 18°C, e.g., have a melting point of at least 25°C, at least 26°C, at least 27°C, at least 28°C, at least 29°C, at least 30°C, at least 31°C, at least 32°C, at least 33°C, at least 34°C, at least 35°C, at least 36°C, at least 37°C, at least 38°C, at least 39°C, at least 40°C, at least 41°C, at least 43°C, at least 43°C, at least 44°C, at least 45°C, at least 45°C, at least 47°C, at least 48°C, at least 49°C, or at least 50°C. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that comprise, consist essentially of, or consist of a mixture of triglycerides that are solid at 18°C, e.g., have a melting point of at most 25°C, at most 26°C, at most 27°C, at most 28°C, at most 29°C, at most 30°C, at most 31°C, at most 32°C, at most 33°C, at most 34°C, at most 35°C, at most 36°C, at most 37°C, at most 38°C, at most 39°C, at most 40°C, at most 41°C, at most 43°C, at most 43°C, at most 44°C, at most 45°C, at most 45°C, at most 47°C, at most 48°C, at most 49°C, or at most 50°C.

[0099] In some embodiments, the pharmaceutical compositions disclosed herein are solid at 18°C, e.g., about 25°C to about 37°C, about 25°C to about 38°C, about 25°C to about 39°C, about 25°C to about 40°C, about 25°C to about 41°C, about 25°C to about 42°C, about 25°C to about 43°C, about 25°C to about 44°C, about 25°C to about 45°C, about 25°C to about 46°C, about 25°C to about 47°C, about 25°C to about 48°C, about 25°C to about 49°C, about 25°C to about 50°C, about 28°C to about 37°C, about 28°C to about 38°C, about 28°C to about 39°C, about 28°C to about 40°C, about 28°C to about 41°C, about 28°C to about 42°C, about 28°C to about 43°C, about 28°C to about 44°C, about 28°C to about 45°C, about 28°C to about 46°C, about 28°C to about 47°C, about 28°C to about 48°C, about 28°C to about 49°C, about 28°C to about 50°C, about 30°C to about 37°C, about 30°C to about 38°C, about 30°C to about 39°C, about 30°C to about 40°C, about 30°C to about 41°C, about 30°C to about 42°C, about 30°C to about 43°C, about 30°C to about 44°C, about 30°C to about 45°C, about 30°C to about 46°C, about 30°C to about 47°C, about 30°C to about 48°C, about 30°C to about 49°C, about 30°C to about 50°C, about 32°C to about 44°C, about 32°C to about 44°C, about 45°C, about 32°C to about 46°C, about 32°C to about 47°C, about 32°C to about 48°C, about 32°C to about 49°C, about 32°C to about 50°C, about 34°C to about 44°C, about 34°C to about 45°C, about 34°C to about 46°C, about 34°C to about 47°C, about 34°C to about 48°C, about 34°C to about 49°C, about 34°C to about 50°C, about 36°C to about 44°C, about 36°C to about 45°C, about 36°C to about 46°C, about 36°C to about 47°C, about 36°C to about 48°C, about 36°C to about 49°C, about 36°C to about 50°C, about 38°C to about 44°C, about 38°C to about 45°C, about 38°C to about 46°C, about 38°C to about 47°C, about 38°C The present invention may comprise one or more hard fats or glycerolipids, which may comprise, consist essentially of, or consist of a mixture of triglycerides having a melting point of about 48°C, about 38°C to about 49°C, about 38°C to about 50°C, about 40°C to about 44°C, about 40°C to about 45°C, about 40°C to about 46°C, about 40°C to about 47°C, about 40°C to about 48°C, about 40°C to about 49°C, about 40°C to about 50°C, about 42°C to about 44°C, about 42°C to about 45°C, about 42°C to about 46°C, about 42°C to about 47°C, about 42°C to about 48°C, about 42°C to about 49°C, or about 42°C to about 50°C.

[0100] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids solid at 18° C., comprising, consisting essentially of, or consisting of a mixture of triglycerides in an amount of, for example, about 10% (by weight), about 15% (by weight), about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), or about 75% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more hard fats or glycerolipids solid at 18° C., comprising, consisting essentially of, or consisting of a mixture of triglycerides in an amount of, for example, at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), or at least 75% (by weight). In some embodiments, pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that are solid at 18° C., comprising, consisting essentially of, or consisting of a mixture of triglycerides in an amount of, for example, at most 10% (by weight), at most 15% (by weight), at most 20% (by weight), at most 25% (by weight), at most 30% (by weight), at most 35% (by weight), at most 40% (by weight), at most 45% (by weight), at most 50% (by weight), at most 55% (by weight), at most 60% (by weight), at most 65% (by weight), at most 70% (by weight), or at most 75% (by weight).

[0101] In some embodiments, the pharmaceutical compositions disclosed herein are solid at 18° C., e.g., about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%. , about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45 The composition may comprise one or more hard fats or glycerolipids that comprise, consist essentially of, or consist of a mixture of triglycerides in an amount of about 50% to about 50%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70% (by weight).

[0102] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and triglycerides. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and triglycerides. 10 -C 18 Monoglyceride, C 10 -C 18 Diglycerides, and C 10 -C 18 Mixture of triglycerides, unsaturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diglycerides, and C 10 -C 20 Mixture of triglycerides, unsaturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diglycerides, and C 10 -C 22 Mixture of triglycerides, unsaturated C 10 -C 24 Monoglyceride, C 10 -C 24 Diglycerides, and C 10 -C 24 Mixture of triglycerides, unsaturated C 12 -C 18 Monoglyceride, C 12 -C 18 Diglycerides, and C 12 -C 18 Mixture of triglycerides, unsaturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diglycerides, and C 12 -C 20 Mixture of triglycerides, unsaturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diglycerides, and C 12 -C 22 Mixture of triglycerides, unsaturated C12 -C 24 Monoglyceride, C 12 -C 24 Diglycerides, and C 12 -C 24 Mixture of triglycerides, unsaturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diglycerides, and C 14 -C 18 Mixture of triglycerides, unsaturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diglycerides, and C 14 -C 20 Mixture of triglycerides, unsaturated C 14 -C 22 Monoglyceride, C 14 -C 22 Diglycerides, and C 14 -C 22 Mixture of triglycerides, unsaturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diglycerides, and C 14 -C 24 Mixture of triglycerides, unsaturated C 16 -C 18 Monoglyceride, C 16 -C 18 Diglycerides, and C 16 -C 18 Mixture of triglycerides, unsaturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diglycerides, and C 16 -C 20 Mixture of triglycerides, unsaturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diglycerides, and C 16 -C 22 Mixture of triglycerides, unsaturated C 16 -C 24 Monoglyceride, C16 -C 24 Diglycerides, and C 16 -C 24 Mixture of triglycerides, unsaturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diglycerides, and C 18 -C 20 Mixture of triglycerides, unsaturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diglycerides, and C 18 -C 22 Mixture of triglycerides, unsaturated C 18 -C 24 Monoglyceride, C 18 -C 24 Diglycerides, and C 18 -C 24 Mixture of triglycerides, unsaturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diglyceride, C 20 -C 22 Mixture of triglycerides, or unsaturated C 22 -C 24 Monoglyceride, C 22 -C 24 Diglycerides, and C 22 -C 24 It may comprise one or more liquid fats or glycerolipids comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0103] In some embodiments, the pharmaceutical compositions disclosed herein are liquid at 18° C. and / or at saturated C 10 -C 18 Monoglyceride, C 10 -C 18 Diglycerides, and C 10 -C 18 Mixture of triglycerides, saturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diglycerides, and C10 -C 20 Mixture of triglycerides, saturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diglycerides, and C 10 -C 22 Mixture of triglycerides, saturated C 10 -C 24 Monoglyceride, C 10 -C 24 Diglycerides, and C 10 -C 24 Mixture of triglycerides, saturated C 12 -C 18 Monoglyceride, C 12 -C 18 Diglycerides, and C 12 -C 18 Mixture of triglycerides, saturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diglycerides, and C 12 -C 20 Mixture of triglycerides, saturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diglycerides, and C 12 -C 22 Mixture of triglycerides, saturated C 12 -C 24 Monoglyceride, C 12 -C 24 Diglycerides, and C 12 -C 24 Mixture of triglycerides, saturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diglycerides, and C 14 -C 18 Mixture of triglycerides, saturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diglycerides, and C 14 -C 20 Mixture of triglycerides, saturated C14 -C 22 Monoglyceride, C 14 -C 22 Diglycerides, and C 14 -C 22 Mixture of triglycerides, saturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diglycerides, and C 14 -C 24 Mixture of triglycerides, saturated C 16 -C 18 Monoglyceride, C 16 -C 18 Diglycerides, and C 16 -C 18 Mixture of triglycerides, saturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diglycerides, and C 16 -C 20 Mixture of triglycerides, saturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diglycerides, and C 16 -C 22 Mixture of triglycerides, saturated C 16 -C 24 Monoglyceride, C 16 -C 24 Diglycerides, and C 16 -C 24 Mixture of triglycerides, saturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diglycerides, and C 18 -C 20 Mixture of triglycerides, saturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diglycerides, and C 18 -C 22 Mixture of triglycerides, saturated C 18 -C 24 Monoglyceride, C 18-C 24 Diglycerides, and C 18 -C 24 Mixture of triglycerides, saturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diglyceride, C 20 -C 22 Mixture of triglycerides, or saturated C 22 -C 24 Monoglyceride, C 22 -C 24 Diglycerides, and C 22 -C 24 It may comprise one or more liquid fats or glycerolipids comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0104] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated C 10 -C 18 Monoglyceride, C 10 -C 18 Diglycerides, and C 10 -C 18 Mixture of triglycerides, saturated and unsaturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diglycerides, and C 10 -C 20 Mixture of triglycerides, saturated and unsaturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diglycerides, and C 10 -C 22 Mixture of triglycerides, saturated and unsaturated C 10 -C 24 Monoglyceride, C 10 -C 24 Diglycerides, and C 10 -C 24 Mixture of triglycerides, saturated and unsaturated C 12 -C 18 Monoglyceride, C 12 -C 18Diglycerides, and C 12 -C 18 Mixture of triglycerides, saturated and unsaturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diglycerides, and C 12 -C 20 Mixture of triglycerides, saturated and unsaturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diglycerides, and C 12 -C 22 Mixture of triglycerides, saturated and unsaturated C 12 -C 24 Monoglyceride, C 12 -C 24 Diglycerides, and C 12 -C 24 Mixture of triglycerides, saturated and unsaturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diglycerides, and C 14 -C 18 Mixture of triglycerides, saturated and unsaturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diglycerides, and C 14 -C 20 Mixture of triglycerides, saturated and unsaturated C 14 -C 22 Monoglyceride, C 14 -C 22 Diglycerides, and C 14 -C 22 Mixture of triglycerides, saturated and unsaturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diglycerides, and C 14 -C 24 Mixture of triglycerides, saturated and unsaturated C 16 -C 18 Monoglyceride, C 16 -C 18Diglycerides, and C 16 -C 18 Mixture of triglycerides, saturated and unsaturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diglycerides, and C 16 -C 20 Mixture of triglycerides, saturated and unsaturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diglycerides, and C 16 -C 22 Mixture of triglycerides, saturated and unsaturated C 16 -C 24 Monoglyceride, C 16 -C 24 Diglycerides, and C 16 -C 24 Mixture of triglycerides, saturated and unsaturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diglycerides, and C 18 -C 20 Mixture of triglycerides, saturated and unsaturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diglycerides, and C 18 -C 22 Mixture of triglycerides, saturated and unsaturated C 18 -C 24 Monoglyceride, C 18 -C 24 Diglycerides, and C 18 -C 24 Mixture of triglycerides, saturated and unsaturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diglyceride, C 20 -C 22 A mixture of triglycerides, or saturated and unsaturated C 22 -C 24 Monoglyceride, C 22 -C 24Diglycerides, and C 22 -C 24 It may comprise one or more liquid fats or glycerolipids comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0105] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that comprise, consist essentially of, or consist of a mixture of mono-, di-, and triglycerides that are liquid at 18°C, e.g., having a melting point of at most 15°C, at most 16°C, at most 17°C, at most 18°C, at most 19°C, or at most 20°C. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that comprise, consist essentially of, or consist of a mixture of mono-, di-, and triglycerides that are liquid at 18°C, e.g., have a melting point between about 0°C to about 5°C, about 0°C to about 10°C, about 0°C to about 15°C, about 0°C to about 20°C, about 0°C to about 22°C, about 0°C to about 25°C, about 5°C to about 10°C, about 5°C to about 15°C, about 5°C to about 20°C, about 5°C to about 22°C, about 5°C to about 25°C, about 10°C to about 15°C, about 10°C to about 20°C, about 10°C to about 22°C, about 10°C to about 25°C, about 15°C to about 20°C, about 15°C to about 22°C, or about 15°C to about 25°C.

[0106] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and / or triglycerides in an amount of, for example, about 10% (by weight), about 15% (by weight), about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), or about 75% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and / or triglycerides, e.g., in an amount of at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), or at least 75% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and / or triglycerides, e.g., in an amount of up to 10% (by weight), up to 15% (by weight), up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), or up to 75% (by weight).

[0107] In some embodiments, the pharmaceutical compositions disclosed herein comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and / or triglycerides, e.g., from about 10% to about 20%, from about 10% to about 25%, from about 10% to about 30%, from about 10% to about 35%, from about 10% to about 40%, from about 10% to about 45%, from about 10% to about 50%, from about 10% to about 55%, from about 10% to about 60%, from about 10% to about 65%, from about 10% to about 70%, , about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to About 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, It may be contained in an amount of about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70% (by weight).

[0108] In some embodiments, the pharmaceutical compositions disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides. Monoglycerides include, but are not limited to, glycerol monomyristoleate, glycerol monopalmitoleate, glycerol monosapienate, glycerol monooleate, glycerol monoelaidate, glycerol monobasenate, glycerol monolinoleate, glycerol monolinoleidate, glycerol monolinolenate, glycerol monostearidonate, glycerol monoeicosenoate, glycerol monomerdate, glycerol monoarachidonate, glycerol monoeicosapentaenoate, glycerol monoerucate, glycerol monodocosahexaenoate, and glycerol mononervonate.

[0109] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated C 10 -C 18 Monoglyceride, unsaturated C 10 -C 20 Monoglyceride, unsaturated C 10 -C 22 Monoglyceride, unsaturated C 10 -C 24 Monoglyceride, unsaturated C 12 -C 18 Monoglyceride, unsaturated C 12 -C 20 Monoglyceride, unsaturated C 12 -C 22 Monoglyceride, unsaturated C 12 -C 24 Monoglyceride, unsaturated C 14 -C 18 Monoglyceride, unsaturated C 14 -C 20 Monoglyceride, unsaturated C 14 -C 22 Monoglyceride, unsaturated C 14 -C 24 Monoglyceride, unsaturated C 16 -C 18 Monoglyceride, unsaturated C16 -C 20 Monoglyceride, unsaturated C 16 -C 22 Monoglyceride, unsaturated C 16 -C 24 Monoglyceride, unsaturated C 18 -C 20 Monoglyceride, unsaturated C 18 -C 22 Monoglyceride, unsaturated C 18 -C 24 Monoglyceride, unsaturated C 20 -C 22 Monoglycerides, or unsaturated C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C ​​and that comprise, consist essentially of, or consist of monoglycerides.

[0110] In some embodiments, the pharmaceutical compositions disclosed herein comprise a saturated C 10 -C 18 Monoglyceride, saturated C 10 -C 20 Monoglyceride, saturated C 10 -C 22 Monoglyceride, saturated C 10 -C 24 Monoglyceride, saturated C 12 -C 18 Monoglyceride, saturated C 12 -C 20 Monoglyceride, saturated C 12 -C 22 Monoglyceride, saturated C 12 -C 24 Monoglyceride, saturated C 14 -C 18 Monoglyceride, saturated C 14 -C 20 Monoglyceride, saturated C 14 -C 22 Monoglyceride, saturated C 14 -C 24 Monoglyceride, saturated C 16 -C 18 Monoglyceride, saturated C 16 -C 20 Monoglyceride, saturated C16 -C 22 Monoglyceride, saturated C 16 -C 24 Monoglyceride, saturated C 18 -C 20 Monoglyceride, saturated C 18 -C 22 Monoglyceride, saturated C 18 -C 24 Monoglyceride, saturated C 20 -C 22 Monoglyceride, or saturated C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C ​​and that comprise, consist essentially of, or consist of monoglycerides.

[0111] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated C 10 -C 18 Mixture of monoglycerides, saturated and unsaturated C 10 -C 20 Mixture of monoglycerides, saturated and unsaturated C 10 -C 22 Mixture of monoglycerides, saturated and unsaturated C 10 -C 24 Mixture of monoglycerides, saturated and unsaturated C 12 -C 18 Mixture of monoglycerides, saturated and unsaturated C 12 -C 20 Mixture of monoglycerides, saturated and unsaturated C 12 -C 22 Mixture of monoglycerides, saturated and unsaturated C 12 -C 24 Mixture of monoglycerides, saturated and unsaturated C 14 -C 18 Mixture of monoglycerides, saturated and unsaturated C 14 -C 20 Mixture of monoglycerides, saturated and unsaturated C 14 -C 22 Mixture of monoglycerides, saturated and unsaturated C 14 -C 24 Mixture of monoglycerides, saturated and unsaturated C16 -C 18 Mixture of monoglycerides, saturated and unsaturated C 16 -C 20 Mixture of monoglycerides, saturated and unsaturated C 16 -C 22 Mixture of monoglycerides, saturated and unsaturated C 16 -C 24 Mixture of monoglycerides, saturated and unsaturated C 18 -C 20 Mixture of monoglycerides, saturated and unsaturated C 18 -C 22 Mixture of monoglycerides, saturated and unsaturated C 18 -C 24 Mixture of monoglycerides, saturated and unsaturated C 20 -C 22 Monoglycerides, or mixtures of saturated and unsaturated C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C ​​and that comprise, consist essentially of, or consist of monoglycerides.

[0112] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, e.g., comprise, consist essentially of, or consist of monoglycerides having a melting point of at most 15°C, at most 16°C, at most 17°C, at most 18°C, at most 19°C, or at most 20°C. In some embodiments, the pharmaceutical compositions disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C ​​and comprise, consist essentially of, or consist of monoglycerides having a melting point between, for example, about 0°C to about 5°C, about 0°C to about 10°C, about 0°C to about 15°C, about 0°C to about 20°C, about 0°C to about 22°C, about 0°C to about 25°C, about 5°C to about 10°C, about 5°C to about 15°C, about 5°C to about 20°C, about 5°C to about 22°C, about 5°C to about 25°C, about 10°C to about 15°C, about 10°C to about 20°C, about 10°C to about 22°C, about 10°C to about 25°C, about 15°C to about 20°C, about 15°C to about 22°C, or about 15°C to about 25°C.

[0113] In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount of, for example, about 10% (by weight), about 15% (by weight), about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), or about 75% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., e.g., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount of at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), or at least 75% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount, e.g., up to 10% (by weight), up to 15% (by weight), up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), or up to 75% (by weight).

[0114] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, %, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, About 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 40% to about 45% The composition may comprise one or more liquid fats or glycerolipids that are liquid at 18° C. and comprise, consist essentially of, or consist of one or more monoglycerides in an amount (by weight) of 5% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70% (by weight).

[0115] Commercially available hard fats or glycerolipids that are solid at 18° C. include, but are not limited to, cocoa butter, saturated C glycerol, which has a melting point of about 33° C. 10 -C18 A mixture of triglycerides (GELUCIRE® 33 / 01), a saturated C 10 -C 18 A mixture of triglycerides (GELUCIRE® 39 / 01) and saturated C 10 -C 18 Commercially available liquid fats or glycerolipids that are liquid at 18° C. include mixtures of triglycerides (GELUCIRE® 43 / 01), including, but not limited to, hydrolyzed corn oil with glycerol monolinoleate (MAISINE™ 35-1, MAISINE™ CC). In some embodiments, hydrolyzed corn oil with glycerol monolinoleate (MAISINE™ 35-1, MAISINE™ CC) contains about 32%-52% monoglycerides, including glycerol monolinoleate, about 40%-50% diglycerides, and about 5%-30% triglycerides.

[0116] The pharmaceutical compositions disclosed herein comprise any ratio of hard fat or glycerolipid that is solid at 18° C. to liquid fat or glycerolipid that is liquid at 18° C. that stabilizes one or more therapeutic compounds disclosed herein in a manner that prevents precipitation of the one or more therapeutic compounds. In some embodiments, the pharmaceutical compositions disclosed herein comprise a ratio of hard fat or glycerolipid that is solid at 18° C. to liquid fat or glycerolipid that is liquid at 18° C., for example, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the pharmaceutical compositions disclosed herein comprise a hard fat or glycerolipid that is solid at 18° C., and a liquid fat or glycerolipid that is liquid at 18° C., e.g., in a ratio of about 5:1 to about 4:1, about 5:1 to about 3:1, about 5:1 to about 2:1, about 5:1 to about 1:1, about 4:1 to about 3:1, about 4:1 to about 2:1, about 4:1 to about 1:1, about 3:1 to about 2:1, about 3:1 to about 1:1, or about 2:1 to about 1:1.

[0117] In some embodiments, the pharmaceutical compositions disclosed herein comprise a hard fat or glycerolipid that is solid at 18° C. and a liquid fat or glycerolipid that is liquid at 18° C., for example, in a ratio of about 1:5, about 1:4, about 1:3, or about 1:2. In some embodiments, the pharmaceutical compositions disclosed herein comprise a hard fat or glycerolipid that is solid at 18° C. and a liquid fat or glycerolipid that is liquid at 18° C., for example, in a ratio of about 1:5 to about 1:4, about 1:5 to about 1:3, about 1:5 to about 1:2, about 1:5 to about 1:1, about 1:4 to about 1:3, about 1:4 to about 1:2, about 1:4 to about 1:1, about 1:3 to about 1:2, about 1:3 to about 1:1, or about 1:2 to about 1:1.

[0118] Hydrophilic Protic Solvents The pharmaceutical compositions disclosed herein may include one or more hydrophilic protic solvents. The main purpose of the hydrophilic protic solvent is to increase the solubility of the biological therapeutic compound in the glycerolipid mixture. The hydrophilic protic solvents disclosed herein are anhydrous and contain one or more glycerolipids disclosed herein and one or more C 14-24 It must be miscible with non-polar compounds such as fatty acids. An example of a suitable hydrophilic protic solvent is a carboxylic acid. A carboxylic acid is an organic acid that contains a carboxyl group (C(=O)OH) attached to the R group. The general formula for a carboxylic acid is R-COOH or R-CO 2 H, where R refers to an alkyl, alkenyl, aryl, or other group. Non-limiting examples of carboxylic acids include methanoic acid (formic acid), ethanoic acid (acetic acid), propanoic acid (propionic acid), butanoic acid (butyric acid), pentanoic acid (valeric acid), hexanoic acid (caproic acid), heptanoic acid (enanthic acid), and octanoic acid (caprylic acid).

[0119] The amount of one or more hydrophilic protic solvents useful in the pharmaceutical compositions disclosed herein is the amount necessary to sufficiently dissolve the biological therapeutic compound. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of one or more hydrophilic protic solvents in an amount of, for example, about 0.01%, about 0.05%, about 0.1%, about 0.5%, about 1% (by weight), about 1.5%, about 2% (by weight), about 2.5% (by weight), about 3% (by weight), about 4% (by weight), about 5% (by weight), about 7.5% (by weight), or about 10% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more hydrophilic protic solvents in an amount, e.g., at least 0.01%, at least 0.05%, at least 0.1%, at least 0.5%, at least 1%, at least 1.5% (by weight), at least 2% (by weight), at least 2.5% (by weight), at least 3% (by weight), at least 4% (by weight), at least 5% (by weight), at least 7.5% (by weight), or at least 10% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more hydrophilic protic solvents in an amount, e.g., at least 0.01%, at most 0.05%, at most 0.1%, at most 0.5%, at most 1%, at most 1.5% (by weight), at most 2% (by weight), at most 1% (by weight), at most 1.5% (by weight), at most 2% (by weight), at most 2.5% (by weight), at most 3% (by weight), at most 4% (by weight), at most 5% (by weight), at most 7.5% (by weight), or at most 10% (by weight).

[0120] In some embodiments, the pharmaceutical compositions disclosed herein contain one or more hydrophilic protic solvents in an amount of, for example, about 0.1% to about 1% (by weight), about 0.1% to about 1.5% (by weight), about 0.1% to about 2% (by weight), about 0.1% to about 2.5% (by weight), about 0.1% to about 5% (by weight), about 0.1% to about 7.5% (by weight), about 0.1% to about 10% (by weight), about 0.5% to about 1% (by weight), about 0.5% to about 1.5% (by weight), about 0.5 In some embodiments, the composition may comprise, consist essentially of, or consist of in an amount of about 1% to about 2% (by weight), about 0.5% to about 2.5% (by weight), about 0.5% to about 5% (by weight), about 0.5% to about 7.5% (by weight), about 0.5% to about 10% (by weight), about 1% to about 1.5% (by weight), about 1% to about 2% (by weight), about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 7.5% (by weight), or about 1% to about 10% (by weight).

[0121] Digestive aid The pharmaceutical compositions disclosed herein may include one or more digestive enhancers. The primary purpose of the one or more digestive enhancers is to increase the solubility of the therapeutic compounds disclosed herein with the glycerolipid mixture, to increase the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds, and / or to improve the availability of the therapeutic compounds disclosed herein, promote the selected biodistribution, thereby improving the pharmacodynamics of the compounds. These improved properties are achieved by the one or more digestive enhancers by creating a lipid pre-digestion formulation of the therapeutic compounds disclosed herein, which promotes and enhances the processing of one or more glycerolipids disclosed herein once the pharmaceutical compositions disclosed herein enter the duodenal region of the small intestine. Such glycerolipid processing allows one or more therapeutic compounds included in the pharmaceutical composition to be absorbed by the intestinal cells along with the digested glycerolipids, and then processed and transported to the lymphatic system. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including one or more bile acids. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including cholic acid. In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive stimulants comprising free fatty acids. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive stimulants comprising oleic acid, steric acid, or linoleic acid. In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 20 The pharmaceutical compositions disclosed herein include one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein include one or more digestive enhancers, including sodium oleate, sodium stearate, and / or sodium linoleate.

[0122] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein, and 2) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acids. In some embodiments, the disclosed pharmaceutical compositions comprise 1) cholic acid as disclosed herein, and 2) one or more C 14 -C 20 and one or more digestive enhancers comprising a free fatty acid. In some embodiments, the disclosed pharmaceutical compositions comprise 1) cholic acid as disclosed herein, and 2) one or more digestive enhancers comprising oleic acid, steric acid, or linoleic acid.

[0123] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein; 2) one or more C 14 -C 24 and 3) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions include one or more of the following: 1) cholic acid as disclosed herein; 2) one or more C 14 -C 20 and 3) one or more C 14 -C 20 and one or more digestive enhancers including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including: 1) cholic acid as disclosed herein, 2) oleic acid, steric acid, and / or linoleic acid, and (3) sodium oleate, sodium stearate, and / or sodium linoleate.

[0124] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers including 1) one or more bile acids disclosed herein, and 2) one or more phospholipids disclosed herein. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers including 1) one or more bile acids disclosed herein, and 2) one or more phospholipids disclosed herein.

[0125] In some embodiments, the disclosed pharmaceutical compositions comprise: 1) one or more of the Cs disclosed herein. 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more C phospholipids, and 2) one or more digestive enhancers comprising one or more phospholipids disclosed herein. 14 -C 20 free fatty acids, and 2) one or more digestive enhancers comprising one or more phospholipids disclosed herein. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers comprising 1) oleic acid, steric acid, and / or linoleic acid, and 2) one or more phospholipids disclosed herein.

[0126] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein; 2) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including 1) one or more bile acids disclosed herein, 2) one or more C2H3O4, 2H4O5, 2H5O6, 2H6O7, 2H8O, 2H9O, 2H10O, 2H11O, 2H12O, 2H2O, 2H3O, 2H4O, 2H5O, 2H6O, 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers comprising 1) cholic acid as disclosed herein, 2) oleic acid, steric acid, and / or linoleic acid, and 3) one or more phospholipids as disclosed herein.

[0127] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein, 2) one or more phospholipids disclosed herein, and 3) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more of: 1) cholic acid as disclosed herein; 2) one or more phospholipids as disclosed herein; and 3) one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more of: 1) cholic acid as disclosed herein; 2) one or more phospholipids as disclosed herein; and 3) one or more C-glycerides as disclosed herein. 14 -C 20 and one or more digestive enhancers including sodium free fatty acids. In some embodiments, the disclosed pharmaceutical compositions include: 1) cholic acid as disclosed herein; 2) one or more phospholipids as disclosed herein; and (3) one or more digestive enhancers including sodium oleate, sodium stearate, and / or sodium linoleate.

[0128] In some embodiments, the disclosed pharmaceutical compositions comprise: 1) one or more of the Cs disclosed herein. 14 -C 24 1) one or more C phospholipids disclosed herein; and 2) one or more C phospholipids disclosed herein. 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more of the C10-11000-stimulants disclosed herein. 14 -C 20 1) one or more C phospholipids disclosed herein; and 2) one or more C phospholipids disclosed herein. 14 -C 20In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions include one or more of: 1) oleic acid, and / or linoleic acid, 2) one or more phospholipids disclosed herein, and 3) one or more C 14 -C 20 and one or more digestive enhancers including sodium free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions include: 1) oleic acid, stearate acid, and / or linoleic acid, 2) one or more phospholipids disclosed herein, and (3) one or more digestive enhancers including sodium oleate, sodium stearate, and / or sodium linoleate.

[0129] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein; 2) one or more C 14 -C 24 free fatty acids, 3) one or more phospholipids disclosed herein, and 4) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions include one or more bile acids disclosed herein, one or more C 14 -C 20 free fatty acids, 3) one or more phospholipids disclosed herein, and 4) one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more of: 1) cholic acid as disclosed herein; 2) oleic acid, steric acid, and / or linoleic acid; 3) one or more phospholipids as disclosed herein; and 4) one or more C glycerides as disclosed herein. 14 -C 20and one or more digestive enhancers including sodium free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including 1) cholic acid as disclosed herein, 2) oleic acid, steric acid, and / or linoleic acid, 3) one or more phospholipids as disclosed herein, 4) sodium oleate, sodium stearate, and / or sodium linoleate.

[0130] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of one or more digestive enhancers in an amount of, for example, about 1% (by weight), about 2.5% (by weight), about 5% (by weight), about 7.5% (by weight), about 10% (by weight), about 12.5% ​​(by weight), about 15% (by weight), about 17.5% (by weight), about 20% (by weight), about 22.5% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), about 75% (by weight), or about 80% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more digestive enhancers in an amount, e.g., at least 1% (by weight), at least 2.5% (by weight), at least 5% (by weight), at least 7.5% (by weight), at least 10% (by weight), at least 12.5% ​​(by weight), at least 15% (by weight), at least 17.5% (by weight), at least 20% (by weight), at least 22.5% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), or at least 75% (by weight).In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, up to 1% (by weight), up to 2.5% (by weight), up to 5% (by weight), up to 7.5% (by weight), up to 10% (by weight), up to 12.5% ​​(by weight), up to 15% (by weight), up to 17.5% (by weight), up to 20% (by weight), up to 22.5% (by weight), up to 25% (by weight), up to It may comprise, consist essentially of, or consist of one or more digestive aids in an amount of 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), or up to 80% (by weight).

[0131] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 10% (by weight), about 1% to about 15% (by weight), about 1% to about 20% (by weight), about 1% to about 25% (by weight), about 2.5% to about 5% (by weight), about 2.5% to about 10% (by weight), about 2.5% to about 15% (by weight), about 2.5% to about 20% (by weight), about 2.5% to about 25% (by weight), about 5% to about 10% (by weight), about 5% to about 15% (by weight), or about 5% to about 20% (by weight). (based on weight), about 5% to about 25% (based on weight), about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to 30%, 20% to 35%, 20% to 40%, 20% to 45%, 20% to 50%, 20% to 55%, 20% to 60%, 20% to 65%, 20% to 70%, 25% to 30%, 25% to 35%, 25% to 40%, 25% to About 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, About 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to About 65%, about 40% to about 70%, about 40% to about 75%, about 40% to about 80%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 45% to about 75%, about 45% to about 80%, about 50% to about 55%, about 50% to about 60%,The composition may comprise, consist essentially of, or consist of one or more digestive enhancers in an amount of about 50% to about 65%, about 50% to about 70%, about 50% to about 75%, about 50% to about 80%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 55% to about 75%, about 55% to about 80%, about 60% to about 65%, about 60% to about 70%, about 60% to about 75%, about 60% to about 80%, about 65% to about 70% (by weight), about 65% to about 75%, about 65% to about 80%, about 70% to about 75%, about 70% to about 80%, or about 75% to about 80%.

[0132] bile acids The pharmaceutical compositions disclosed herein may include one or more bile acids. The main purpose of the bile acids is to increase the solubility of the therapeutic compounds disclosed herein in the glycerolipid mixture, to increase the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds, and / or to improve the availability of the therapeutic compounds disclosed herein, to promote the selected biodistribution, thereby improving the pharmacodynamics of the compounds. Furthermore, as disclosed in Example 2, the bile acids disclosed herein may be combined with one or more glycerolipids and / or one or more free C2H3-binding domains disclosed herein. 14-24Improves the solubility of the therapeutic compounds disclosed herein in fatty acids. Improved solubility properties are achieved by bile acids by preventing recrystallization of the therapeutic compounds during solidification when the molten pharmaceutical composition is cooled to room temperature (18°C-20°C). Improved pharmacokinetic properties are achieved by bile acids by breaking down the lipid components of the pharmaceutical compositions disclosed herein through their surfactant properties into smaller lipid structures that mimic emulsion droplets, thereby facilitating the emulsification process. The "emulsion droplets" recruit coeliacs and create a larger surface area where pancreatic lipase can digest the hard fatty glycerolipids present therein, ultimately facilitating intestinal cell absorption and subsequent chylomicron formation. Bile acids are involved in signaling for the initiation of chylomicron formation. Thus, the inclusion of bile acids in lipid formulations maximizes this signaling pathway and the production of chylomicrons. As a result, the improved pharmacodynamic properties provided by bile acids result from increasing the availability of the therapeutic compound by increasing its content in chylomicrons before it enters the circulatory system and facilitating its delivery to compartments such as the brain, where it then crosses membranes such as the blood-brain barrier and the choroid plexus.

[0133] Bile acids, amphiphilic molecules with an HLB greater than 12, have a specific chemical structure that differs from regular aliphatic surfactants due to the presence of a large, rigid, flat, hydrophobic portion of the steroid nucleus with 2-4 hydroxyl groups. Specifically, bile acids contain the following basic components: (1) 4 rings, (2) a 5- / 8-carbon side chain terminating in a carboxylic acid, and (3) several hydroxyl groups (the position / number of which varies among the various salts). The rings are ascribed letters A, B, C, and D based on their distance from the side chain bearing the -COOH group, with the D ring being the furthest away (as well as 1 C smaller than the other rings), as explained below. The β-hydroxyl group points up / out, the α-group points down, and all bile acids have a 3-hydroxyl group derived from their cholesterol precursor. The chemical structure of the bile salts makes this emulsification route useful according to the teachings of the present disclosure, and thus synthetic surfactants do not work.

[0134] Examples of bile acids include, but are not limited to, chenodeoxycholic acid, cholic acid, dafachronic acid, deoxycholic acid, glycocholic acid, glycohenodeoxycholic acid, lithocholic acid, taurochenodeoxycholic acid, taurocholic acid, and any stereoisomers thereof. Cholic acid and chenodeoxycholic acid are called primary bile acids, while deoxycholic acid (converted from cholic acid) and lithocholic acid (converted from chenodeoxycholic acid) are called secondary bile acids. Taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile acids that serve as the basis for the bile salts found in bile.

[0135] There is a direct correlation between the amount of bile acid present in the pharmaceutical compositions disclosed herein and the improved properties observed. Thus, the more bile acid present in the pharmaceutical compositions disclosed herein, the greater the improvement in solubility, absorption, and availability of the therapeutic composition. Also, the upper limit of bile acid included in the pharmaceutical compositions disclosed herein is not limited to the solubility point of the bile acid. Thus, the pharmaceutical compositions disclosed herein can include a supersaturated amount of bile acid. Thus, the upper limit of bile acid that can be included in the pharmaceutical compositions disclosed herein is its critical micelle concentration (CMC). In addition to the improved properties mentioned above, a further advantage of the supersaturated amount of bile acid is the resulting nanoparticle formation of crystalline bile acid in the pharmaceutical compositions disclosed herein. Without wishing to be limited by one theory, the bile acid nanoparticles dissolve when exposed to the alkaline environment of the small intestine to form bile salts, which in turn can act as a reservoir that further promotes the emulsification process of the pharmaceutical compositions disclosed herein.

[0136] The amount of bile acid useful in the pharmaceutical compositions disclosed herein is an amount less than its CMC. In some embodiments, the amount of bile acid useful in the pharmaceutical compositions disclosed herein is an amount less than its CMC and supersaturated. In some embodiments, the pharmaceutical compositions disclosed herein are, for example, about 0.1% (by weight), about 0.5% (by weight), about 1.0% (by weight), about 1.0% (by weight), about 1.5% (by weight), about 2.0% (by weight), about 2.5% (by weight), about 3.0% (by weight), about 3.5% (by weight), about 4.0% (by weight), about 4.5% (by weight), about 5.0% (by weight), about 6.0% (by weight), about 7.0% (by weight), about 8.0% (by weight), about 9.0% (by weight), about 10.0% (by weight), about 11.0% (by weight), about 12.0% (by weight), about 13.0% (by weight), about 14.0% (by weight), about 15.0% (by weight), about 16.0% (by weight), about 17.0% (by weight), about 18.0% (by weight), about 19.0% (by weight), about 20.0% (by weight), about 21.0% (by weight), about 22.0% (by weight), about 23.0% (by weight), about 24.0% (by weight), about 25.0% (by weight), about 26.0% (by weight), about 27.0% (by weight), about 28.0% (by weight), about 29.0% (by weight), about 30.0% (by weight), about 31.0% (by weight), about 32.0% (by weight), about 33.0% (by weight), about 34.0% (by weight), about 35.0% (by (by weight), about 5.5% (by weight), about 6.0% (by weight), about 6.5% (by weight), about 7.0% (by weight), about 7.5% (by weight), about 8.0% (by weight), about 8.5% (by weight), about 9.0% (by weight), about 9.5% (by weight), or about 10.0% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more bile acids in an amount, e.g., at least 0.1% (by weight), at least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), or at least 10.0% (by weight).In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, up to 0.1% (by weight), up to 0.5% (by weight), up to 1.0% (by weight), up to 1.5% (by weight), up to 2.0% (by weight), up to 2.5% (by weight), up to 3.0% (by weight), up to 3.5% (by weight), up to 4.0% (by weight), up to 4.5% (by weight), up to 5.0% (by weight), up to It may comprise, consist essentially of, or consist of one or more bile acids in an amount of at most 5.5% (by weight), up to 6.0% (by weight), up to 6.5% (by weight), up to 7.0% (by weight), up to 7.5% (by weight), up to 8.0% (by weight), up to 8.5% (by weight), up to 9.0% (by weight), up to 9.5% (by weight), or up to 10.0% (by weight).

[0137] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5. .0%, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% The composition may comprise, consist essentially of, or consist of one or more bile acids in an amount of about 7.0%, about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight).

[0138] In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of one or more bile acids, e.g., at a concentration of up to 0.01 mM, up to 0.025 mM, up to 0.05 mM, up to 0.075 mM, up to 0.1 mM, up to 0.25 mM, up to 0.5 mM, up to 0.75 mM, up to 1 mM, or up to 5 mM. In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more bile acids at a concentration of, e.g., about 0.01 mM to about 0.05 mM, about 0.01 mM to about 0.1 mM, about 0.01 mM to about 0.5 mM, about 0.01 mM to about 1 mM, about 0.01 mM to about 5 mM, about 0.05 mM to about 0.1 mM, about 0.05 mM to about 0.5 mM, about 0.05 mM to about 1 mM, about 0.05 mM to about 5 mM, about 0.1 mM to about 0.5 mM, about 0.1 mM to about 1 mM, about 0.1 mM to about 5 mM, or about 1 mM to about 5 mM.

[0139] C 14-24 fatty acid The pharmaceutical compositions disclosed herein contain one or more free C 14-24 The fatty acids may include carboxylic acids with long unbranched hydrocarbon chains that may be either saturated or unsaturated and are hydrophobic molecules with an HLB of less than 4. 14-24 The primary purpose of the fatty acids is to increase the solubility of the therapeutic compounds disclosed herein in the glycerolipid mixture and to increase the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds. The improved solubility properties are due to their property of being a solvent that promotes the dissolution of the therapeutic compounds disclosed herein, and the free C 14-24 The improved absorption properties are achieved by promoting and increasing the formation of micelles by breaking up larger emulsion droplets, thereby mimicking the lipid digestion products of triglycerides, i.e. free fatty acids, which are then absorbed by the free C 14-24 This is achieved by the fatty acids disclosed herein. 14-24The fatty acid increases the uptake of micelles containing one or more therapeutic compounds into intestinal cells. Furthermore, as disclosed in Example 2, the free C 14-24 Fatty acids improve the solubility of the bile salts disclosed herein.

[0140] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated free C 14 -C 16 Fatty acids, unsaturated free C 14 -C 18 Fatty acids, unsaturated free C 14 -C 20 Fatty acids, unsaturated free C 14 -C 22 Fatty acids, unsaturated free C 14 -C 24 Fatty acids, unsaturated free C 16 -C 18 Fatty acids, unsaturated free C 16 -C 20 Fatty acids, unsaturated free C 16 -C 22 Fatty acids, unsaturated free C 16 -C 24 Fatty acids, unsaturated free C 18 -C 20 Fatty acids, unsaturated free C 18 -C 22 Fatty acids, unsaturated free C 18 -C 24 Fatty acids, unsaturated free C 20 -C 22 Fatty acids, or unsaturated free C 22 -C 24 One or more free C groups comprising, consisting essentially of, or consisting of fatty acids 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise omega-3 unsaturated free C fatty acids. 18 -C 22 Fatty acids, ω-5 unsaturated free C 18 -C 22 Fatty acids, ω-6 unsaturated free C 18 -C 22 Fatty acids, ω-7 unsaturated free C 18 -C 22 Fatty acids, ω-9 unsaturated free C 18 -C 22Fatty acids, ω-10 unsaturated free C 18 -C 22 Fatty acids, ω-11 unsaturated free C 18 -C 22 Fatty acids, or ω-12 unsaturated free C 18 -C 22 One or more free C groups containing, consisting essentially of, or consisting of fatty acids 14-24 It may contain fatty acids.

[0141] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated free C 14 -C 16 Fatty acids, saturated free C 14 -C 18 Fatty acids, saturated free C 14 -C 20 Fatty acids, saturated free C 14 -C 22 Fatty acids, saturated free C 14 -C 24 Fatty acids, saturated free C 16 -C 18 Fatty acids, saturated free C 16 -C 20 Fatty acids, saturated free C 16 -C 22 Fatty acids, saturated free C 16 -C 24 Fatty acids, saturated free C 18 -C 20 Fatty acids, saturated free C 18 -C 22 Fatty acids, saturated free C 18 -C 24 Fatty acids, saturated free C 20 -C 22 Fatty acids, or saturated free C 22 -C 24 One or more free C groups comprising, consisting essentially of, or consisting of fatty acids 14-24 It may contain fatty acids.

[0142] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated free C 14 -C 16 Mixture of fatty acids, saturated and unsaturated free C 14 -C 18Mixture of fatty acids, saturated and unsaturated free C 14 -C 20 Mixture of fatty acids, saturated and unsaturated free C 14 -C 22 Mixture of fatty acids, saturated and unsaturated free C 14 -C 24 Mixture of fatty acids, saturated and unsaturated free C 16 -C 18 Mixture of fatty acids, saturated and unsaturated free C 16 -C 20 Mixture of fatty acids, saturated and unsaturated free C 16 -C 22 Mixture of fatty acids, saturated and unsaturated free C 16 -C 24 Mixture of fatty acids, saturated and unsaturated free C 18 -C 20 Mixture of fatty acids, saturated and unsaturated free C 18 -C 22 Mixture of fatty acids, saturated and unsaturated free C 18 -C 24 Mixture of fatty acids, saturated and unsaturated free C 20 -C 22 Mixture of fatty acids, or saturated and unsaturated free C 22 -C 24 One or more free C fatty acids comprising, consisting essentially of, or consisting of a mixture of fatty acids 14-24 It may contain fatty acids.

[0143] free C 14-24Non-limiting examples of fatty acids are palmitic acid (hexadecenoic acid), palmitrinolenic acid, palmitidonic acid, palmitovaccenic acid, palmitoleic acid, sapienic acid, 4-hexadecenoic acid, stearic acid (octadecenoic acid), α-linolenic acid, stearidonic acid, α-eleostearic acid, β-eleostearic acid, pumic acid, 7,10,13-octadecatrienoic acid, 12-octadecenoic acid, linoleic acid, and linolelaidic acid. Gamma-linolenic acid, calendic acid, pinolenic acid, bactic acid, ruminic acid, oleic acid, elaidic acid, petroselinic acid, arachidic acid (eicosanoic acid), dihomo-alpha-linolenic acid, eicosinic acid, tetraenoic acid, eicosapentaenoic acid, 9,12,15-eicosatrienoic acid, beta-eicosinic acid, tetraenoic acid, dihomo-linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, paulinic acid, 7,10,13-eicosanoic acid, These include satrienoic acid, gondoic acid, 8,11-eicosadienoic acid, meazinic acid, gadoleic acid, 8-eicosenoic acid, behenic acid (docosanoic acid), clupanodonic acid, docosahexaenoic acid, adrenic acid, osbondic acid, erucic acid, lignoceric acid (tetracosanoic acid), 9,12,15,18,21-tetracosapentaenoic acid, 6,9,12,15,18,21-tetracosahexaenoic acid, and nervonic acid.

[0144] Free C useful in the pharmaceutical compositions disclosed herein 14-24 The amount of fatty acid is an amount that does not adversely affect the pharmacokinetics of the therapeutic compound with which it is formulated. In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C in an amount of, for example, about 1% (by weight), about 2.5% (by weight), about 5% (by weight), about 7.5% (by weight), about 10% (by weight), about 12.5% ​​(by weight), about 15% (by weight), about 17.5% (by weight), about 20% (by weight), about 22.5% (by weight), about 25% (by weight), about 35% (by weight), about 30% (by weight), about 40% (by weight), about 50% (by weight), about 60% (by weight), about 70% (by weight), or about 75% (by weight). 14-24In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise one or more free C in an amount of, for example, at least 1% (by weight), at least 2.5% (by weight), at least 5% (by weight), at least 7.5% (by weight), at least 10% (by weight), at least 12.5% ​​(by weight), at least 15% (by weight), at least 17.5% (by weight), at least 20% (by weight), at least 22.5% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 50% (by weight), at least 60% (by weight), at least 70% (by weight), or at least 75% (by weight). 14-24 In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of fatty acids. 14-24 It can comprise, consist essentially of, or consist of fatty acids.

[0145] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 10% (by weight), about 1% to about 15% (by weight), about 1% to about 20% (by weight), about 1% to about 25% (by weight), about 2.5% to about 5% (by weight), about 2.5% to about 10% (by weight), about 2.5% to about 15% (by weight), about 2.5% to about 20% (by weight), about 2.5% to about 25% (by weight), about 2.5% to about 30% (by weight), about 5% to about 10% (by weight), about 5% ~15% (by weight), approximately 5% to approximately 20% (by weight), approximately 5% to approximately 25% (by weight), approximately 5% to approximately 30% (by weight), approximately 10% to approximately 15% (by weight), approximately 10% to approximately 20% (by weight), approximately 10% to approximately 25% (by weight), approximately 10% to approximately 30% (by weight), Approximately 10% to approximately 40% (weight basis), approximately 10% to approximately 45% (weight basis), approximately 10% to approximately 50% (weight basis), approximately 10% to approximately 60% (weight basis), approximately 10% to approximately 70% (weight basis), approximately 15% to approximately 20% (weight basis), approximately 15% to approximately 25% (weight basis), approximately 15% to approximately 30% (weight basis), about 15% to about 40% (weight basis), about 15% to about 45% (weight basis), about 15% to about 50% (weight basis), about 15% to about 60% (weight basis), about 15% to about 70% (weight basis), about 20% to about 25% (weight basis), about 20% to about 30% (weight basis), about 2 0% to approx. 40% (weight basis), approx. 20% to approx. 45% (weight basis), approx. 20% to approx. 50% (weight basis), approx. 20% to approx. 60% (weight basis), approx. about 30% to about 70% (by weight), about 30% to about 75% (by weight), about 35% to about 40% (by weight), about 35% to about 50% (by weight), about 35% to about 60% (by weight), about 35% to about 70% (by weight), about 35% to about 75% (by weight), about 40% to about 50% (by weight), about 40% to about 60% (by weight), about 40% to about 70% (by weight), about 40% to about 75% (by weight), about 50% to about 60% (by weight), about 50% to about 70% (by weight), or about 60% to about 70% (by weight) of one or more free C. 14-24It can comprise, consist essentially of, or consist of fatty acids.

[0146] In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C, e.g., at a concentration of up to 0.01 mM, up to 0.025 mM, up to 0.05 mM, up to 0.075 mM, up to 0.1 mM, up to 0.25 mM, up to 0.5 mM, up to 0.75 mM, up to 1 mM, up to 1.25 mM, up to 1.5 mM, up to 1.75 mM, or up to 2 mM. 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids, for example, about 0.01 mM to about 0.05 mM, about 0.01 mM to about 0.1 mM, about 0.01 mM to about 0.5 mM, about 0.01 mM to about 1 mM, about 0.01 mM to about 1.25 mM, about 0.01 mM to about 1.5 mM, about 0.01 mM to about 1.75 mM, about 0.01 mM to about 2 mM, about 0.05 mM to about 0.1 mM, about 0.05 mM to about 0.5 mM, about 0.05 mM to about 1 mM, about 0.05 mM to about 1.25 mM, about 0.05 mM to about 1. ... One or more free C at a concentration of about 1.75 mM, about 0.05 mM to about 2 mM, about 0.1 mM to about 0.5 mM, about 0.1 mM to about 1 mM, about 0.1 mM to about 1.25 mM, about 0.1 mM to about 1.5 mM, about 0.1 mM to about 1.75 mM, about 0.1 mM to about 2 mM, about 0.5 mM to about 1 mM, about 0.5 mM to about 1.25 mM, about 0.5 mM to about 1.5 mM, about 0.5 mM to about 1.75 mM, about 0.5 mM to about 2 mM, about 1 mM to about 1.25 mM, about 1 mM to about 1.5 mM, about 1 mM to about 1.75 mM, or about 15 mM to about 2 mM 14-24 It can comprise, consist essentially of, or consist of fatty acids.

[0147] Phospholipids The pharmaceutical compositions disclosed herein may include one or more phospholipids. Similar to the bile acids disclosed herein, the phospholipids disclosed herein break down the lipid components of the pharmaceutical compositions disclosed herein through their surfactant properties into smaller lipid structures that mimic emulsion droplets, thereby facilitating the emulsification process. The "emulsion droplets" recruit coryopsis and create a larger surface area where pancreatic lipase can digest the hard fatty glycerolipids present inside. Furthermore, the phospholipids disclosed herein, together with the free fatty acid surfactants disclosed herein, promote the formation of micelles by associating with lipid digestion products of triglycerides, and then enhancing the association of triglyceride digestion products with fatty acid transporters, thereby enhancing the absorption of lipid molecules and associated therapeutic compounds into enterocytes.

[0148] The structure of phospholipids generally includes a hydrophobic tail of one or more fatty acids and a hydrophilic head containing a phosphate functional group, is amphiphilic in nature, and has an HLB greater than 12. Phospholipids include, but are not limited to, phosphoglycerides and phosphosphingolipids. Phosphoglycerides have a general structure that includes a glycerol backbone with two fatty acids esterified to the first and second hydroxyl groups of glycerol and a phosphate group esterified to the third hydroxyl group of glycerol. An alcohol group is esterified to the phosphate group of the phosphoglyceride. Phosphoglycerides always have two fatty acids, usually one fatty acid is saturated and the other fatty acid is unsaturated. Phosphoglycerides are generally classified according to the specific alcohol group present on the phosphate group, such as ethanolamine, choline, serine, or inositol. Non-limiting examples of phosphoglycerides include phosphatidic acid (phosphatidate) (PA), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), cardiolipin, and phosphoinositides, including phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidylinositol diphosphate (PIP2), and phosphatidylinositol triphosphate (PIP3).

[0149] Although structurally different, phosphosphingolipids also have a polar head and two non-polar tails.Phosphosphingolipids have a general structure that includes a long-chain amino alcohol sphingosine backbone with a fatty acid that forms an amide bond with the amino group of the sphingosine backbone and a phosphate group that is esterified to the hydroxyl group of the sphingosine backbone.Non-limiting examples of phosphosphingolipids include ceramide phosphorylethanolamine (Cer-PE) and ceramide phosphorylcholine (Cer-PC) and ceramide phosphorylglycerol (Cer-PG).

[0150] In addition to its amphiphilic nature, phospholipids can be zwitterionic phospholipids. Zwitterionic phospholipids are fully ionized molecules that contain an equal number of positively charged and negatively charged functional groups and are electrically neutral. Non-limiting examples of zwitterionic phospholipids include phosphatidylethanolamine (PE), phosphatidylcholine (PC), ceramide phosphorylethanolamine (Cer-PE) and ceramide phosphorylcholine (Cer-PC).

[0151] The phospholipids disclosed herein include lectins. Lectins are amphiphilic mixtures of glycerophospholipids. In some embodiments, the lectin comprises a mixture of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and phosphatidic acid. In some embodiments, the lectin comprises 19%-21% phosphatidylcholine, 8%-20% phosphatidylethanolamine, 20%-21% phosphatidylinositol, and 5%-11% phospholipids including phosphatidylserine and phosphatidic acid.

[0152] In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more phospholipids in an amount of, for example, about 1.0% (by weight), about 1.5% (by weight), about 2.0% (by weight), about 2.5% (by weight), about 3.0% (by weight), about 3.5% (by weight), about 4.0% (by weight), about 4.5% (by weight), about 5.0% (by weight), about 5.5% (by weight), about 6.0% (by weight), about 6.5% (by weight), about 7.0% (by weight), about 7.5% (by weight), about 8.0% (by weight), about 8.5% (by weight), about 9.0% (by weight), about 9.5% (by weight), or about 10.0% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more phospholipids in an amount, e.g., at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), or at least 10.0% (by weight).In some embodiments, the pharmaceutical compositions disclosed herein comprise, consist essentially of, or can consist of one or more phospholipids in an amount, e.g., of up to 1.0% (by weight), up to 1.5% (by weight), up to 2.0% (by weight), up to 2.5% (by weight), up to 3.0% (by weight), up to 3.5% (by weight), up to 4.0% (by weight), up to 4.5% (by weight), up to 5.0% (by weight), up to 5.5% (by weight), up to 6.0% (by weight), up to 6.5% (by weight), up to 7.0% (by weight), up to 7.5% (by weight), up to 8.0% (by weight), up to 8.5% (by weight), up to 9.0% (by weight), up to 9.5% (by weight), or up to 10.0% (by weight).

[0153] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2 ... ~ about 4.0%, ~ about 2.0% to about 5.0%, ~ about 2.0% to about 6.0%, ~ about 2.0% to about 7.0%, ~ about 2.0% to about 8.0%, ~ about 2.0% to about 9.0%, ~ about 2.0% to about 10.0%, ~ about 3.0% to about 4.0%, ~ about 3.0% to about 5.0%, ~ about 3.0% to about 6.0%, ~ about 3.0% to about 7.0%, ~ about 3.0% to about 8.0%, ~ about 3.0% to about 9.0%, ~ about 3.0% to about 1 0.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8 0.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight).

[0154] C 14-24 Fatty Acid Surfactant The pharmaceutical compositions disclosed herein contain one or more free C 14-24 The fatty acid surfactants may include fatty acid surfactants. Fatty acid surfactants include carboxylic acids with long unbranched hydrocarbon chains that may be either saturated or unsaturated associated with alkali metal or other metal ions, and are hydrophobic amphiphilic molecules with an HLB greater than 12. 14-24 The primary purpose of the fatty acid surfactant is to increase the solubility of the therapeutic compounds disclosed herein with the glycerolipid mixture and to increase the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds. The improved solubility properties are due to the increased free C14-24 The improved absorption properties are achieved by the fatty acid surfactants through the interaction of their carboxylic acid functional groups with the sodium ions present on the therapeutic compound, which neutralize the charge and facilitate compound interaction with the hydrophobic glycolipid mixture. The improved absorption properties are achieved by promoting and increasing the formation of mixed micelles by breaking up larger emulsion droplets, thereby mimicking triglycerides, i.e., lipid digestion products of free fatty acids, and thus reducing the amount of free C. 14-24 This is achieved by the fatty acid surfactant. 14-24 The fatty acid surfactants increase the uptake of micelles containing one or more therapeutic compounds into intestinal cells. 14-24 The fatty acid surfactants are free C in combination with alkali metals, such as lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or alkaline earth metals, such as beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra). 14-24 It is a fatty acid.

[0155] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated free C 14 -C 16 Fatty acid surfactant, unsaturated free C 14 -C 18 Fatty acid surfactant, unsaturated free C 14 -C 20 Fatty acid surfactant, unsaturated free C 14 -C 22 Fatty acid surfactant, unsaturated free C 14 -C 24 Fatty acid surfactant, unsaturated free C 16 -C 18 Fatty acid surfactant, unsaturated free C 16 -C 20 Fatty acid surfactant, unsaturated free C 16 -C 22 Fatty acid surfactant, unsaturated free C 16 -C 24 Fatty acid surfactant, unsaturated free C 18 -C20 Fatty acid surfactant, unsaturated free C 18 -C 22 Fatty acid surfactant, unsaturated free C 18 -C 24 Fatty acid surfactant, unsaturated free C 20 -C 22 Fatty acid surfactant, or unsaturated free C 22 -C 24 One or more free C groups comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may include a fatty acid surfactant. 18 -C 22 Fatty acid surfactant, ω-5 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-6 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-7 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-9 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-10 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-11 unsaturated free C 18 -C 22 Fatty acid surfactant, or ω-12 unsaturated free C 18 -C 22 one or more free C surfactants, comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 A fatty acid surfactant may be included.

[0156] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated free C 14 -C 16 Fatty acid surfactant, saturated free C 14 -C 18 Fatty acid surfactant, saturated free C 14 -C 20 Fatty acid surfactant, saturated free C 14 -C 22 Fatty acid surfactant, saturated free C 14 -C 24Fatty acid surfactant, saturated free C 16 -C 18 Fatty acid surfactant, saturated free C 16 -C 20 Fatty acid surfactant, saturated free C 16 -C 22 Fatty acid surfactant, saturated free C 16 -C 24 Fatty acid surfactant, saturated free C 18 -C 20 Fatty acid surfactant, saturated free C 18 -C 22 Fatty acid surfactant, saturated free C 18 -C 24 Fatty acid surfactant, saturated free C 20 -C 22 Fatty acid surfactant, or saturated free C 22 -C 24 One or more free C groups comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 A fatty acid surfactant may be included.

[0157] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated free C 14 -C 16 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 18 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 18 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C18 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 20 -C 22 Mixture of fatty acid surfactants, or saturated and unsaturated free C 22 -C 24 One or more free C surfactants comprising, consisting essentially of, or consisting of a mixture of fatty acid surfactants 14-24 A fatty acid surfactant may be included.

[0158] free C 14-24Non-limiting examples of fatty acid surfactants include sodium palmitate (hexadecanoate), sodium palmitrinoleate, sodium palmitidate, sodium palmitovaccenate, sodium palmitoleate, sodium sapienate, sodium 4-hexadecenoate, sodium stearate (octadecenoate), sodium alpha-linolenate, sodium stearate, sodium alpha-eleostearate, sodium beta-eleostearate, sodium pumitarate, sodium 7,10,13-octadecatrienoate, sodium 12-octadecenoate, sodium linoleate, and sodium linoleidate. Sodium gamma-linolenate, sodium calendarate, sodium pinolenate, sodium vasinate, sodium luminate, sodium oleate, sodium elaidate, sodium petroselinate, sodium arachidate (eicosanoate), sodium dihomo-alpha-linolenate, sodium eicosatetraenoate, sodium eicosapentaenoate, sodium 9,12,15-eicosatrienoate, sodium beta-eicosatetraenoate, sodium dihomo-gamma-linolenate, sodium arachidonate, sodium paulinate, sodium 7,10,1 Includes sodium 3-eicosatrienoate, sodium gondoate, sodium 8,11-eicosadienoate, sodium mesinate, sodium gadoleate, sodium 8-eicosenoate, sodium behenate (docosanoate), sodium clupanodonate, sodium docosahexaenoate, sodium adrenate, sodium osbondate, sodium erucate, sodium lignocerate (tetracosanate), sodium 9,12,15,18,21-tetracosapentaenoate, sodium 6,9,12,15,18,21-tetracosahexaenoate, and sodium nervonate.

[0159] One or more free C that may be included in the pharmaceutical compositions disclosed herein 14-24 The lower limit of the fatty acid surfactant is an amount sufficient to solubilize the therapeutic compound and impart its improved absorption characteristics. One or more free C that can be included in the pharmaceutical compositions disclosed herein 14-24The upper limit for a fatty acid surfactant is its micellar concentration (CMC).

[0160] One or more free C useful in the pharmaceutical compositions disclosed herein 14-24 The amount of fatty acid surfactant is an amount below its CMC. In some embodiments, the pharmaceutical compositions disclosed herein comprise one or more free C in an amount of, e.g., about 0.1% (by weight), about 0.5% (by weight), about 1.0% (by weight), about 1.0% (by weight), about 1.5% (by weight), about 2.0% (by weight), about 2.5% (by weight), about 3.0% (by weight), about 3.5% (by weight), about 4.0% (by weight), about 4.5% (by weight), about 5.0% (by weight), about 5.5% (by weight), about 6.0% (by weight), about 6.5% (by weight), about 7.0% (by weight), about 7.5% (by weight), about 8.0% (by weight), about 8.5% (by weight), about 9.0% (by weight), about 9.5% (by weight), or about 10.0% (by weight). 14-24 In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein can comprise one or more free C in an amount of, for example, at least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), or at least 10.0% (by weight). 14-24It can comprise, consist essentially of, or consist of a fatty acid surfactant. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of a fatty acid surfactant, e.g., at most 0.1% (by weight), at most 0.5% (by weight), at most 1.0% (by weight), at most 1.5% (by weight), at most 2.0% (by weight), at most 2.5% (by weight), at most 3.0% (by weight), at most 3.5% (by weight), at most 4.0% (by weight), at most 4.5% (by weight), or at most 5.0% (by weight). free carbon in an amount of up to 5.0% (by weight), up to 5.5% (by weight), up to 6.0% (by weight), up to 6.5% (by weight), up to 7.0% (by weight), up to 7.5% (by weight), up to 8.0% (by weight), up to 8.5% (by weight), up to 9.0% (by weight), up to 9.5% (by weight), or up to 10.0% (by weight) 14-24 It may comprise, consist essentially of, or consist of a fatty acid surfactant.

[0161] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, , about 0.5% to about 5.0%, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4. one or more free C in an amount of 0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight); 14-24 It may comprise, consist essentially of, or consist of a fatty acid surfactant.

[0162] In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C at a concentration of, e.g., at most 5 μM, at most 10 μM, at most 15 μM, at most 20 μM, at most 25 μM, at most 1 μM, or at most 35 μM. 14-24 In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of a fatty acid surfactant, for example, about 1 μM to about 5 μM, about 1 μM to about 10 μM, about 1 μM to about 15 μM, about 1 μM to about 20 μM, about 1 μM to about 25 μM, about 1 μM to about 30 μM, about 1 μM to about 35 μM, about 5 μM to about 10 μM, about 5 μM to about 15 μM, about 5 μM to about 20 μM, about 5 μM to about 25 μM, about 5 μM to about 30 μM, about 5 μM to about 35 μM, about 10 μM to about 15 μM, about 1 ...1 μM to about 25 μM, about 1 μM to about 30 μM, about 1 μM to about 35 μM, about 10 μM to about 15 μM, about 1 μM to about 20 μM, about 1 μM to about 20 μM, about 1 μM to about 35 μM, about 1 μM to about 15 μM, about 1 μM to about 20 μM, about 1 μM to about 20 μM, about 1 μM to about 35 μM, about 1 μM to about 15 μM, about 1 μM to about 20 μM, about 1 μM to about 20 μM, about 1 μM to about 35 μM, about 1 μM to about 15 μM, about 1 μM to about 20 μM, about μM, approximately 10 μM to approximately 20 μM, approximately 10 μM to approximately 25 μM, approximately 10 μM to approximately 30 μM, approximately 10 μM to approximately 35 μM, approximately 15 μM to approximately 20 μM, approximately 15 μM to approximately 25 μM, approximately 15 μM to approximately 30 μM, approximately 15 μM one or more free C at a concentration of ~about 35 μM, about 20 μM to about 25 μM, about 20 μM to about 30 μM, about 20 μM to about 35 μM, about 25 μM to about 30 μM, about 25 μM to about 35 μM, or about 30 μM to about 35 μM 14-24 It may comprise, consist essentially of, or consist of a fatty acid surfactant.

[0163] Curcumin Aspects of the present specification partially disclose curcumin. In some embodiments, the pharmaceutical compositions disclosed herein may include curcumin. Curcumin is a phenolic pigment extracted from Curcuma longa. Despite being a pharmacologically bioactive molecule, curcumin can promote gallbladder contraction, making this compound useful as a digestive enhancer as disclosed herein. Gallbladder contraction is a key process in fat absorption, thus providing the important benefit of increasing the formation of mixed micelles by breaking up larger emulsion droplets, thereby increasing the uptake of micelles containing one or more therapeutic compounds into enterocytes. As shown in Example 3, although a highly insoluble compound, curcumin is soluble using the formulations disclosed herein.

[0164] The amount of curcumin useful in the pharmaceutical compositions disclosed herein is a therapeutically effective amount or an amount effective for promoting gallbladder contraction.In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of curcumin in an amount of, for example, about 0.1%, about 0.5%, about 1% (by weight), about 1.5%, about 2% (by weight), about 2.5% (by weight), about 3% (by weight), about 4% (by weight), about 5% (by weight), about 7.5% (by weight), or about 10% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of curcumin in an amount, e.g., at least 0.1%, at least 0.5%, at least 1%, at least 1.5% (by weight), at least 2% (by weight), at least 2.5% (by weight), at least 3% (by weight), at least 4% (by weight), at least 5% (by weight), at least 7.5% (by weight), or at least 10% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of curcumin in an amount, e.g., at most 0.1%, at most 0.5%, at most 1%, at most 1.5% (by weight), at most 2% (by weight), at most 1% (by weight), at most 1.5% (by weight), at most 2% (by weight), at most 2.5% (by weight), at most 3% (by weight), at most 4% (by weight), at most 5% (by weight), at most 7.5% (by weight), or at most 10% (by weight).

[0165] In some embodiments, the pharmaceutical compositions disclosed herein contain curcumin in an amount of, for example, about 0.1% to about 1% (by weight), about 0.1% to about 1.5% (by weight), about 0.1% to about 2% (by weight), about 0.1% to about 2.5% (by weight), about 0.1% to about 5% (by weight), about 0.1% to about 7.5% (by weight), about 0.1% to about 10% (by weight), about 0.5% to about 1% (by weight), about 0.5% to about 1.5% (by weight), about 0.5% to about 2% (by weight), about 0.5% to about 2.5% (by weight), about 0.5% to about 5% (by weight), about 0.5% to about 7.5% (by weight), about 0.5% to about 10% (by weight), about 1% to about 1.5% (by weight), about 1% to about 2% (by weight), about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 7.5% (by weight), or about 1% to about 10% (by weight).

[0166] Glycol Polymer Aspects of the present specification in part disclose glycol polymers. In some embodiments, the pharmaceutical compositions disclosed herein may include one or more glycol polymers.

[0167] The pharmaceutical compositions disclosed herein may include a sufficient amount of stabilizer to stabilize the free acid or free base present in the therapeutic compounds disclosed herein. In other aspects of this embodiment, the pharmaceutical compositions disclosed herein may include, for example, less than about 40% (by weight), less than about 35% (by weight), less than about 30% (by weight), less than about 25% (by weight), less than about 20% (by weight), less than about 19% (by weight), less than about 18% (by weight), less than about 17% (by weight), less than about 16% (by weight), less than about 15% (by weight), less than about 14% (by weight), or less than about 40% (by weight). The composition may comprise an amount of stabilizer of less than about 1% (by weight), less than about 13% (by weight), less than about 12% (by weight), less than about 11% (by weight), less than about 10% (by weight), less than about 9% (by weight), less than about 8% (by weight), less than about 7% (by weight), less than about 6% (by weight), less than about 5% (by weight), less than about 4% (by weight), less than about 3% (by weight), less than about 2% (by weight), or less than about 1%.In other aspects of this embodiment, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1% to about 5% (by weight), about 1% to about 7% (by weight), about 1% to about 10% (by weight), about 1% to about 12% (by weight), about 1% to about 15% (by weight), about 1% to about 18% (by weight), about 1% to about 20% (by weight), about 2% to about 5% (by weight), about 2% to about 7% (by weight), about 2% to about 10% (by weight), about 2% to about 12% (by weight), about 2% to about 15% (by weight), about 2% to about 18% (by weight), about 2% to about 2 0% (by weight), about 3% to about 5% (by weight), about 3% to about 7% (by weight), about 3% to about 10% (by weight), about 3% to about 12% (by weight), about 3% to about 15% (by weight), about 3% to about 18% (by weight), about 3% to about 20% (by weight), about 4% Approximately 5% (by weight), approximately 4% to approximately 7% (by weight), approximately 4% to approximately 10% (by weight), approximately 4% to approximately 12% (by weight), approximately 4% to approximately 15% (by weight), approximately 4% to approximately 18% (by weight), approximately 4% to approximately 20% (by weight), approximately 5% to approximately 7% (by weight), approximately 5% ~about 10% (by weight), about 5% to about 12% (by weight), about 5% to about 15% (by weight), about 5% to about 18% (by weight), about 5% to about 20% (by weight), about 6% to about 7% (by weight), about 6% to about 10% (by weight), about 6% to about 12% (by weight), Approx. 6% to approx. 15% (weight basis), approx. 6% to approx. 18% (weight basis), approx. 6% to approx. 20% (weight basis), approx. 7% to approx. 10% (weight basis), approx. 7% to approx. (by weight), about 8% to about 10% (by weight), about 8% to about 12% (by weight), about 8% to about 15% (by weight), about 8% to about 18% (by weight), about 8% to about 20% (by weight), about 9% to about 10% (by weight), about 9% to about 12% (by weight), about 9% to about 15% (by weight), about 9% to about 18% (by weight), about 9% to about 20% (by weight), about 10% to about 12% (by weight), about 10% to about 15% (by weight), about 10% to about 18% (by weight), or about 10% to about 20% (by weight).

[0168] The stabilizer disclosed herein is not a solvent because it is used in an amount that does not cause substantial dissolution of solute.Therefore, the amount of stabilizer used in the solid solution composition disclosed herein causes the dissolution of 85% or less of the therapeutic compound disclosed herein.In various aspects of this embodiment, the amount of stabilizer used in the solid solution composition disclosed herein causes the dissolution of, for example, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less of the therapeutic compound disclosed herein.

[0169] In embodiments, the glycol polymer may comprise a pharma- ceutically acceptable PEG polymer. PEG polymers, also known as polyethylene oxide (PEO) or polyoxyethylene (POE) polymers, are prepared by polymerization of ethylene oxide and are commercially available over a wide range of molecular weights, from 100 g / mol to 10,000,000 g / mol. Low molecular weight PEG polymers are liquids or low melting point solids, while high molecular weight PEG polymers are solids. In aspects of this embodiment, the PEG polymer used as a stabilizer is a liquid PEG polymer. In aspects of this embodiment, the PEG polymer has a molecular weight of, for example, 100 g / mol or less, 200 g / mol or less, 300 g / mol or less, 400 g / mol or less, 500 g / mol or less, 600 g / mol or less, 700 g / mol or less, 800 g / mol or less, 900 g / mol or less, or 1000 g / mol or less.

[0170] PEG polymers include, but are not limited to, PEG100, PEG200, PEG300, PEG400, PEG500, PEG600, PEG700, PEG800, PEG900, PEG1000, PEG1100, PEG1200, PEG1300, PEG1400, PEG1500, PEG1600, PEG1700, PEG1800, PEG1900, PEG2000, PEG2100, PEG2200, PEG2300, PEG2400, PEG2500, PEG2600, PEG2700, PEG2800, PEG2900, PEG3000, PEG3500, PEG4000, PEG4500, PEG4600, PEG4700, PEG4800, PEG4900, PEG5000, PEG5100, PEG5200, PEG5300, PEG5400, PEG5500, PEG5600, PEG5700, PEG5800, PEG5900, PEG6000, PEG6100, PEG6200, PEG6300, PEG6400, PEG6500, PEG6600, PEG6700, PEG6800, PEG6900, PEG7000, PEG7100, PEG7200, PEG7300, PEG7400, PEG7500, PEG7600, PEG7700, PEG7800, PEG7900, PEG7900, PEG7000, PEG7100, PEG7200, PEG7300, PEG74 250, PEG 3350, PEG 3500, PEG 3750, PEG 4000, PEG 4250, PEG 4500, PEG 4750, PEG 5000, PEG 5500, PEG 6000, PEG 6500, PEG 7000, PEG 7500, PEG 8000, PEG 8500, PEG 9000, PEG 9500, PEG 10,000, PEG 11,000, PEG 12,000, PEG 13,000, PEG 14,000, PEG 15,000, PEG 16,000, PEG 17,000, PEG 18,000, PEG 19,000, or PEG 20,000.

[0171] In another embodiment, the glycol polymer may comprise a pharma- ceutically acceptable polypropylene glycol (PPG) polymer. PPG polymers, also known as polypropylene oxide (PPO) polymers or polyoxypropylene (POP) polymers, are prepared by polymerization of propylene oxide and are commercially available over a wide range of molecular weights from 100 g / mol to 10,000,000 g / mol. Low molecular weight PPG polymers are liquids or low melting solids, while high molecular weight PPG polymers are solids. In aspects of this embodiment, the PPG polymer used as a stabilizer is a liquid PPG polymer. In aspects of this embodiment, the PPG polymer has a molecular weight of, for example, 100 g / mol or less, 200 g / mol or less, 300 g / mol or less, 400 g / mol or less, 500 g / mol or less, 600 g / mol or less, 700 g / mol or less, 800 g / mol or less, 900 g / mol or less, or 1000 g / mol or less.

[0172] PPG polymers include, but are not limited to, PPG100, PPG200, PPG300, PPG400, PPG500, PPG600, PPG700, PPG800, PPG900, PPG1000, PPG1100, PPG1200, PPG1300, PPG1400, PPG1500, PPG1600, PPG1700, PPG1800, PPG1900, PPG2000, PPG2100, PPG2200, PPG2300, PPG2400, PPG2500, PPG2600, PPG2700, PPG2800, PPG2900, PPG3000, PPG325 0, PPG3350, PPG3500, PPG3750, PPG4000, PPG4250, PPG4500, PPG4750, PPG5000, PPG5500, PPG6000, PPG6500, PPG7000, PPG7500, PPG8000, PPG8500, PPG9000, PPG9500, PPG10,000, PPG11,000, PPG12,000, PPG13,000, PPG14,000, PPG15,000, PPG16,000, PPG17,000, PPG18,000, PPG19,000, or PPG20,000.

[0173] In some embodiments, the pharmaceutical compositions disclosed herein do not include a glycol polymer. In aspects of these embodiments, the pharmaceutical compositions disclosed herein do not include a PEG polymer. In other aspects of these embodiments, the pharmaceutical compositions disclosed herein do not include a PGG polymer. In yet other aspects of these embodiments, the pharmaceutical compositions disclosed herein do not include both a PEG polymer and a PGG polymer.

[0174] Emission Effect In embodiments, a significant amount of the therapeutic compound present in the pharmaceutical composition disclosed herein is delivered to or enters the lipid digestion and / or absorption pathway.In an aspect of this embodiment, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90% or about 95% of the therapeutic compound present in the pharmaceutical composition disclosed herein is delivered to or enters the lipid digestion and / or absorption pathway.In another aspect of this embodiment, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the therapeutic compound present in the pharmaceutical composition disclosed herein is delivered to or enters the lipid digestion and / or absorption pathway. In still other aspects of this embodiment, up to 10%, up to 20%, up to 30%, up to 40%, up to 50%, up to 60%, up to 70%, up to 80%, up to 90%, or up to 95% of the therapeutic compound present in the pharmaceutical compositions disclosed herein is delivered to or enters the lipid digestion and / or absorption pathways.

[0175] In yet other aspects of this embodiment, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 90%, about 10% to about 100%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 20% to about 100%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to about 100%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 90%, about 40% to about 100%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 90%, about 50% to about 100%, about Between 60% and about 70%, between 60% and about 80%, between 60% and about 90%, between 60% and about 100%, between 70% and about 80%, between 70% and about 90%, between 70% and about 100%, between 80% and about 90%, between 80% and about 100%, or between 90% and about 100% is delivered to or enters the lipid digestion and / or absorption pathways.

[0176] In an embodiment, a small amount of the therapeutic compound present in the pharmaceutical composition disclosed herein is absorbed by capillary blood vessels and directly enters the blood.In an aspect of this embodiment, at most 1%, at most 5%, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 95% of the therapeutic compound present in the pharmaceutical composition disclosed herein is absorbed by capillary blood vessels and directly enters the blood. In aspects of this embodiment, about 1% to about 10%, about 1% to about 20%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 1% to about 60%, about 1% to about 70%, about 1% to about 80%, about 1% to about 90%, about 1% to about 95%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 90%, about 10% to about 95%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 20% to about 95%, about 3 0% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to about 95%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 90%, about 40% to about 95%, about 50% to about 60%, about 50% to about 70%, about 50 % to about 80%, about 50% to about 90%, about 50% to about 95%, about 60% to about 70%, about 60% to about 80%, about 60% to about 90%, about 60% to about 95%, about 70% to about 80%, about 70% to about 90%, about 70% to about 95%, about 80% to about 90%, about 80% to about 95%, or about 90% to about 95% is absorbed by the capillaries and enters the blood directly.

[0177] Formulation Procedure The inclusion of one or more digestive enhancers for one or more therapeutic compounds in the pharmaceutical compositions disclosed herein is applicable to any therapeutic compound that is administered by a route of administration where the ingestion of the compound is achieved by absorption through the digestive tract (e.g., oral delivery, etc.). However, the formulation of the pharmaceutical compositions disclosed herein depends on the solubility of the therapeutic compound in one or more glycerolipids used to formulate the pharmaceutical composition. Thus, the formulation of any one particular therapeutic compound disclosed herein is achieved by the method described below.

[0178] As a first step, it is first determined whether the selected therapeutic compound can be formulated using 1) glycerolipids, including at least one liquid fat (glycerolipid that is liquid at 18°C) and at least one hard fat (glycerolipid that is solid at 18°C), and 2) one or more digestive enhancers. In some embodiments, one or more liquid and hard fats are first heated, and one or more digestive enhancers are solubilized in the glycerolipid mixture. Once the dissolution of the digestive enhancer is complete, the temperature of the mixture can be adjusted, if appropriate, and then the selected therapeutic compound is dissolved in the heated mixture to incorporate the compound. Such a manufacturing procedure is useful when formulating a therapeutic compound that is easily solubilized in a lipid mixture. In some embodiments, one or more liquid fats are first heated, and one or more digestive enhancers are solubilized in the liquid fat. Once the dissolution of the digestive enhancer is complete, the temperature of the mixture can be adjusted, if appropriate, and then the selected therapeutic compound is dissolved in the heated mixture to incorporate the compound. Once the therapeutic compound is completely dissolved, one or more hard fats are then added to the heated mixture. Such manufacturing procedures are useful when formulating lipophilic therapeutic compounds. In some embodiments, one or more digestive enhancers are heated first, and then the selected therapeutic compound is dissolved in the heated mixture to incorporate the compound. Once dissolution of the therapeutic compound is complete, the temperature of the mixture can be adjusted, if appropriate, and then one or more liquid fats are added and incorporated into the mixture. Once dissolution of the one or more liquid fats is complete, then one or more hard fats are added and incorporated into the mixture. Such manufacturing procedures are useful when formulating therapeutic compounds that are highly insoluble in lipid mixtures. The initial heating step in all procedures is performed at a temperature sufficient to dissolve the one or more digestive enhancers and the selected therapeutic compound, which can be empirically determined based on the melting points of the selected ingredients. Generally, this temperature ranges from about 60°C to about 170°C. Any subsequent adjustments to the heat when one or more liquid fats and / or one or more malted fats are being added to the mixture are performed at a temperature sufficient to melt the hard fats, which can be empirically determined based on the melting points of the hard fats used in the formulation.Generally, this temperature ranges from about 40°C to about 60°C.

[0179] The entrapped mixture is then cooled to room temperature, at which point stirring is stopped and the mixture is transferred to a suitable container and allowed to solidify. Once cooled, the pharmaceutical composition can optionally be tested for stability by reheating to a temperature sufficient to melt the composition. The reheating step is performed at a temperature sufficient to melt the glycerolipid component and can be empirically determined based on the melting point of the hard fat used in the formulation. Generally, this temperature ranges from 40°C to 50°C. The selection of one or more digestive enhancers is generally not a critical component in this process, since bile acids, free fatty acids, phospholipids or free fatty acid surfactants can all be used in any combination to achieve the pharmaceutical compositions disclosed herein. If the selected therapeutic compound remains stably entrapped in the glycerolipid mixture, successful formulation is achieved. However, if the selected therapeutic compound is not entrapped or precipitates in the heated glycerolipid mixture during the cooling process, the reheating step, or during storage at room temperature, the compound cannot be formulated according to this process. As shown in Example 2, all preparation methods involve a complete melt phase where upon cooling nanocrystallization of some components occurs, which is documented in the XRPD spectra.

[0180] Examples 4-11 exemplify therapeutic compounds formulated according to this process. These examples also demonstrate two formulation subgroups. In one subgroup, the presence of one or more digestive enhancers does not appreciably improve the solubility of the therapeutic compound in the glycerolipid matrix. Instead, the presence of the digestive enhancers serves to improve the bioavailability of the therapeutic compound. Example 4, which relates to fenofibrate, and Example 5, which relates to cannabidiol, exemplify therapeutic compounds in this formulation subgroup. In one subgroup, the presence of one or more digestive enhancers is necessary to achieve solubility of the therapeutic compound in the glycerolipid matrix and improve the bioavailability of the compound. Example 3 and Examples 6-11, which relate to curcumin, exemplify therapeutic compounds in this formulation subgroup.

[0181] If the therapeutic compound cannot be formulated by the above process, the therapeutic compound is evaluated for the presence of an ionizable functional group, such as an organic acid functional group (e.g., a carboxylic acid functional group or a sulfonic acid functional group, etc.) or an organic base functional group (e.g., an amine functional group, etc.). In some embodiments, if the therapeutic compound contains an organic acid functional group, a component containing an organic base functional group is mixed with the therapeutic compound to form an anhydrous salt form of the therapeutic compound. In some embodiments, if the therapeutic compound contains an organic base functional group, a simple organic acid functional group is used to form an anhydrous salt form of the therapeutic compound. In these preparation methods, the formation of an anhydrous salt of the therapeutic compound allows the formulation of the pharmaceutical compositions disclosed herein and is therefore a prerequisite for the formation of the glycerolipid matrix. The ionic bonding that must occur to form the anhydrous salt is an unexpected result, since the components are not in an aqueous environment and therefore dissolution of the ions cannot occur. The presence of one or more hard fats in the mixture prior to the formation of the anhydrous salt of the therapeutic compound prevents dissolution of the therapeutic compound and causes the compound to precipitate from the mixture.

[0182] Alternatively, therapeutic compounds that contain ionic functional groups can be formulated by neutralizing the compound to its non-ionic form.Many therapeutic compounds are presented in ionic form.For example, organic acids, such as NSAIDs, are often presented as salts, such as, but not limited to, alkali or alkaline earth metal salts.Other therapeutic compounds, such as, but not limited to, amines, are often presented as mineral acid salts, such as hydrochloride salts, for example, amitriptyline and ketamine.Such therapeutic compounds can also be used in their neutral non-ionic form by releasing the carboxylic acid or amine from its salt.

[0183] For example, as illustrated in Example 12 for naproxen, therapeutic compounds containing a carboxylic acid functional group can exist in either the free carboxylic acid form or the carboxylate salt form. The method has found that while only either ionic form is insoluble in the glycerolipid mixture, when the free carboxylic acid form of naproxen is mixed with the carboxylate salt form of naproxen, the anhydrous salt of naproxen dissolves and is then stably incorporated into the glycerolipid matrix (see Table 27, naproxen formulation NAPF3). Similarly, the free carboxylic acid form of naproxen can be mixed with the carboxylate salt form of naproxen to obtain a glycerolipid matrix. 14-24 Mixing with fatty acid surfactants results in the formation and dissolution of anhydrous salts of naproxen and their subsequent stable incorporation into the glycerolipid matrix (see Table 27, naproxen formulation NAPF2). These findings for naproxen have been extended to other therapeutic compounds containing organic acids where mixing with a component containing an organic base functional group forms anhydrous salts of the therapeutic compound that are then incorporated into the glycerolipid matrix (see Examples 12-17). The organic base-containing component, whether present as a therapeutic component or an additional component, can be an alkali metal or alkaline earth metal salt and acts as a crystallization inhibitor to slow the rate of crystallization.

[0184] Similarly, as disclosed in Example 12, the carboxylate form of naproxen was 14-24Mixing with fatty acids results in the formation and dissolution of the anhydrous salt of naproxen and its subsequent stable incorporation into the glycerolipid matrix (see Table 27, naproxen formulations NAPF1 and NAPF4). The findings for naproxen extend to other therapeutic compounds containing organic bases whose mixture with components containing organic acid functional groups forms anhydrous salt forms (see Examples 18-20). For example, Example 18 describes seven formulations for aprepitant (APRF1-APRF7). In each case, the formation of the anhydrous salt of the therapeutic compound first resulted in the dissolution of the anhydrous salt of naproxen and its subsequent stable incorporation into the glycerolipid matrix.

[0185] Based on these findings, when a therapeutic compound contains an organic acid functional group, one of the following processes can be used to formulate the pharmaceutical compositions disclosed herein. In some embodiments, one or more liquid fats (glycerolipids that are liquid at 18° C.) and one or more digestive enhancers containing an organic base are first heated, and then a selected therapeutic compound containing an organic acid functional group is dissolved in the heated mixture to incorporate the compound and form an anhydrous salt of the therapeutic compound. Once the therapeutic compound is completely dissolved, one or more hard fats are then added to the heated mixture. In some embodiments, one or more digestive enhancers containing an organic base are first heated, and then a selected therapeutic compound containing an organic acid functional group is dissolved in the heated mixture to incorporate the compound and form an anhydrous salt of the therapeutic compound. Once the therapeutic compound is completely dissolved, one or more hard fats are then added to the heated mixture. In some embodiments, one or more digestive enhancers containing an organic base are first heated, and then a selected therapeutic compound containing an organic acid functional group is dissolved in the heated mixture to incorporate the compound and form an anhydrous salt of the therapeutic compound. Once dissolution of the therapeutic compound is complete, the temperature of the mixture can be adjusted, if appropriate, and then one or more liquid fats are added and incorporated into the mixture. Once dissolution of the one or more liquid fats is complete, then one or more hard fats are added and incorporated into the mixture. The initial heating step in all procedures is performed at a temperature sufficient to dissolve the one or more digestive facilitators and the selected therapeutic compound, and can be empirically determined based on the melting points of the selected ingredients. Generally, this temperature range is from about 60°C to about 170°C. Any subsequent adjustments to the heat when one or more liquid fats and / or one or more malted fats are being added to the mixture are performed at a temperature sufficient to melt the hard fats, and can be empirically determined based on the melting points of the hard fats used in the formulation. Generally, this temperature range is from about 40°C to about 60°C.

[0186] Regardless of which process is used, the entrapped mixture is then cooled to room temperature, at which point stirring is stopped and the mixture is transferred to a suitable container and allowed to solidify. Additionally, once cooled, the pharmaceutical composition can optionally be tested for stability by reheating to a temperature sufficient to melt the composition. The reheating step is performed at a temperature sufficient to melt the glycerolipid component and can be empirically determined based on the melting point of the hard fat used in the formulation. Generally, this temperature ranges from 40°C to 50°C. As mentioned above, depending on the method, a carboxylic acid or carboxylate salt form may be required, but the selection of one or more digestive enhancers is generally not a critical component in this process, since bile acids in the appropriate ionic form, free fatty acids, phospholipids or free fatty acid surfactants can all be used in any combination to achieve the pharmaceutical compositions disclosed herein. If the selected therapeutic compound remains stably entrapped in the glycerolipid mixture, successful formulation is achieved.

[0187] Based on these findings, when the therapeutic compound contains an organic base functional group, one of the following processes can be used to formulate the pharmaceutical compositions disclosed herein. In some embodiments, one or more liquid fats (glycerolipids that are liquid at 18° C.) and one or more digestive enhancers containing an organic acid are first heated, and then a selected therapeutic compound containing an organic base functional group is dissolved in the heated mixture to incorporate the compound and form an anhydrous salt of the therapeutic compound. Once the therapeutic compound is completely dissolved, one or more hard fats are then added to the heated mixture. In some embodiments, one or more digestive enhancers containing an organic acid are first heated, and then a selected therapeutic compound containing an organic base functional group is dissolved in the heated mixture to incorporate the compound and form an anhydrous salt of the therapeutic compound. Once the therapeutic compound is completely dissolved, one or more hard fats are then added to the heated mixture. In some embodiments, one or more digestive enhancers containing an organic acid are first heated, and then a selected therapeutic compound containing an organic base functional group is dissolved in the heated mixture to incorporate the compound and form an anhydrous salt of the therapeutic compound. Once dissolution of the therapeutic compound is complete, the temperature of the mixture can be adjusted, if appropriate, and then one or more liquid fats are added and incorporated into the mixture. Once dissolution of the one or more liquid fats is complete, then one or more hard fats are added and incorporated into the mixture. The initial heating step in all procedures is performed at a temperature sufficient to dissolve the one or more digestive facilitators and the selected therapeutic compound, and can be empirically determined based on the melting points of the selected ingredients. Generally, this temperature range is from about 60°C to about 170°C. Any subsequent adjustments to the heat when one or more liquid fats and / or one or more malted fats are being added to the mixture are performed at a temperature sufficient to melt the hard fats, and can be empirically determined based on the melting points of the hard fats used in the formulation. Generally, this temperature range is from about 40°C to about 60°C.

[0188] Regardless of which process is used, the entrapped mixture is then cooled to room temperature, at which point stirring is stopped and the mixture is transferred to a suitable container and allowed to solidify. Additionally, once cooled, the pharmaceutical composition can optionally be tested for stability by reheating to a temperature sufficient to melt the composition. The reheating step is performed at a temperature sufficient to melt the glycerolipid component and can be empirically determined based on the melting point of the hard fat used in the formulation. Generally, this temperature ranges from 40°C to 50°C. The selection of one or more digestive enhancers is generally not a critical component in this process, since bile acids, free fatty acids, phospholipids or free fatty acid surfactants can all be used in any combination to achieve the pharmaceutical compositions disclosed herein. If the selected therapeutic compound remains stably entrapped in the glycerolipid mixture, successful formulation is achieved. Example 11 illustrates a therapeutic compound formulated according to this process.

[0189] In some embodiments, the pharmaceutical product comprises one or more therapeutic compounds, one or more glycerolipids, and one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0190] In some embodiments, the pharmaceutical comprises from about 0.1% to about 20% (by weight) of one or more therapeutic compounds, from about 80% to about 99% (by weight) of one or more glycerolipids, and from about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises from about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, from about 80% to about 99% (by weight) of one or more glycerolipids, and from about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0191] In some embodiments, the pharmaceutical comprises from about 0.1% to about 20% (by weight) of one or more therapeutic compounds, from about 75% to about 95% (by weight) of one or more glycerolipids, and from about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises from about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, from about 75% to about 95% (by weight) of one or more glycerolipids, and from about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0192] In some embodiments, the pharmaceutical comprises from about 0.1% to about 30% (by weight) of one or more therapeutic compounds, from about 50% to about 85% (by weight) of one or more glycerolipids, and from about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises from about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, from about 50% to about 85% (by weight) of one or more glycerolipids, and from about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0193] In some embodiments, the pharmaceutical comprises from about 0.1% to about 30% (by weight) of one or more therapeutic compounds, from about 45% to about 80% (by weight) of one or more glycerolipids, and from about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises from about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, from about 45% to about 80% (by weight) of one or more glycerolipids, and from about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0194] In some embodiments, the pharmaceutical comprises from about 0.1% to about 30% (by weight) of one or more therapeutic compounds, from about 30% to about 55% (by weight) of one or more glycerolipids, and from about 40% to about 80% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises from about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, from about 30% to about 55% (by weight) of one or more glycerolipids, and from about 40% to about 80% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0195] In some embodiments, the pharmaceutical product comprises one or more therapeutic compounds, one or more hard fats, one or more liquid fats, and one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0196] In some embodiments, the pharmaceutical comprises about 0.1% to about 20% (by weight) of one or more therapeutic compounds, about 25% to about 70% (by weight) of one or more hard fats, about 25% to about 70% (by weight) of one or more liquid fats, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 25% to about 70% (by weight) of one or more hard fats, about 25% to about 70% (by weight) of one or more liquid fats, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24fatty acid surfactants, or any combination thereof.

[0197] In some embodiments, the pharmaceutical product comprises about 0.1% to about 20% (by weight) of one or more therapeutic compounds, about 25% to about 70% (by weight) of one or more hard fats comprising glycerolipids, about 25% to about 70% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical product comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 25% to about 70% (by weight) of one or more hard fats comprising glycerolipids, about 25% to about 70% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0198] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 20% (by weight) of one or more therapeutic compounds, from about 25% to about 70% (by weight) of C 10-C 24 One or more hard fats, including triglycerides, about 25% to about 70% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical product comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 25% to about 70% (by weight) of C 10 -C 24 One or more hard fats, including triglycerides, about 25% to about 70% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0199] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 20% (by weight) of one or more therapeutic compounds, from about 25% to about 70% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 25% to about 70% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and from about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises from about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, from about 25% to about 70% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 25% to about 70% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0200] In some embodiments, the pharmaceutical comprises about 0.1% to about 20% (by weight) of one or more therapeutic compounds, about 35% to about 55% (by weight) of one or more hard fats, about 25% to about 50% (by weight) of one or more liquid fats, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 35% to about 55% (by weight) of one or more hard fats, about 25% to about 50% (by weight) of one or more liquid fats, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24fatty acid surfactants, or any combination thereof.

[0201] In some embodiments, the pharmaceutical comprises about 0.1% to about 20% (by weight) of one or more therapeutic compounds, about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, about 25% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, about 25% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0202] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 20% (by weight) of one or more therapeutic compounds, from about 35% to about 55% (by weight) of C 10 -C24 One or more hard fats, including triglycerides, about 25% to about 50% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical product comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 35% to about 55% (by weight) of C 10 -C 24 One or more hard fats, including triglycerides, about 25% to about 50% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0203] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 20% (by weight) of one or more therapeutic compounds, from about 35% to about 55% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 25% to about 50% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises one or more therapeutic compounds at about 25 mg / mL to about 600 mg / mL, about 35% to about 55% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 25% to about 50% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 30% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0204] In some embodiments, the pharmaceutical comprises about 0.1% to about 30% (by weight) of one or more therapeutic compounds, about 15% to about 65% (by weight) of one or more hard fats, about 15% to about 50% (by weight) of one or more liquid fats, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 15% to about 65% (by weight) of one or more hard fats, about 15% to about 50% (by weight) of one or more liquid fats, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24fatty acid surfactants, or any combination thereof.

[0205] In some embodiments, the pharmaceutical comprises about 0.1% to about 30% (by weight) of one or more therapeutic compounds, about 15% to about 65% (by weight) of one or more hard fats comprising glycerolipids, about 15% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 15% to about 65% (by weight) of one or more hard fats comprising glycerolipids, about 15% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0206] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 30% (by weight) of one or more therapeutic compounds, from about 15% to about 65% (by weight) of C 10 -C24 One or more hard fats, including triglycerides, about 15% to about 50% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical product comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 15% to about 65% (by weight) of C 10 -C 24 One or more hard fats, including triglycerides, about 15% to about 50% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0207] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 30% (by weight) of one or more therapeutic compounds, from about 15% to about 65% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 15% to about 50% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 15% to about 65% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 15% to about 50% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 5% to about 25% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0208] In some embodiments, the pharmaceutical comprises about 0.1% to about 30% (by weight) of one or more therapeutic compounds, about 20% to about 55% (by weight) of one or more hard fats, about 15% to about 45% (by weight) of one or more liquid fats, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 20% to about 55% (by weight) of one or more hard fats, about 15% to about 45% (by weight) of one or more liquid fats, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24fatty acid surfactants, or any combination thereof.

[0209] In some embodiments, the pharmaceutical comprises about 0.1% to about 30% (by weight) of one or more therapeutic compounds, about 20% to about 55% (by weight) of one or more hard fats comprising glycerolipids, about 15% to about 45% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 20% to about 55% (by weight) of one or more hard fats comprising glycerolipids, about 15% to about 45% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0210] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 30% (by weight) of one or more therapeutic compounds, from about 20% to about 55% (by weight) of C 10-C 24 One or more hard fats, including triglycerides, from about 15% to about 45% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical product comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 20% to about 55% (by weight) of C. 10 -C 24 One or more hard fats, including triglycerides, from about 15% to about 45% (by weight) of C 10 -C 24 Mono-, C 10 -C 24 Ji and C 10 -C 24 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0211] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 30% (by weight) of one or more therapeutic compounds, from about 20% to about 55% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 15% to about 45% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 One or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises one or more therapeutic compounds at about 25 mg / mL to about 600 mg / mL, about 20% to about 55% (by weight) of saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 One or more hard fats, including a mixture of triglycerides, from about 15% to about 45% (by weight) C 16 -C 18 Mono-, C 16 -C 18 Ji and C 16 -C 18 one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 20% to about 45% (by weight) of one or more digestive enhancers. In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof.

[0212] In some embodiments, the pharmaceutical agent comprises one or more therapeutic compounds, one or more hard fats, one or more liquid fats, and one or more bile acids. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more bile acids of the above embodiments comprise cholic acid. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more bile acids of the above embodiments comprise cholic acid.

[0213] In some embodiments, the pharmaceutical comprises from about 0.1% to about 20% (by weight) of one or more therapeutic compounds, from about 25% to about 70% (by weight) of one or more hard fats, from about 25% to about 70% (by weight) of one or more liquid fats, and from about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical comprises from about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, from about 25% to about 70% (by weight) of one or more hard fats, from about 25% to about 70% (by weight) of one or more liquid fats, and from about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, the one or more bile acids of the above embodiments comprise cholic acid. In some embodiments, the one or more therapeutic compounds of the above embodiments comprise a hydrophilic therapeutic compound, an amphiphilic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof, and the one or more bile acids of the above embodiments comprise cholic acid.

[0214] In some embodiments, the pharmaceutical comprises about 0.1% to about 20% (by weight) of one or more therapeutic compounds, about 25% to about 70% (by weight) of one or more hard fats comprising glycerolipids, about 25% to about 70% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical comprises about 25 mg / mL to about 600 mg / mL of one or more therapeutic compounds, about 25% to about 70% (by weight) of one or more hard fats comprising glycerolipids, about 25% to about 70% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, one or more of the therapeutic compounds of the above embodiments include a hydrophilic therapeutic compound, an amphipathic therapeutic compound, a hydrophobic therapeutic compound, a lipophilic therapeutic compound, a therapeutic compound comprising an organic acid functional group, a therapeutic compound comprising an organic base functional group, or any combination thereof. In some embodiments, one or more of the bile acids of the above embodiments include cholic acid. In some embodiments, one or more of the therapeutic compounds of the above embodiments include a hydrophilic t...

Claims

1. A pharmaceutical composition comprising: a) one or more therapeutic compounds; b) one or more glycerolipids; and c) one or more digestive enhancers.

2. The one or more therapeutic compounds may be from about 0.1% to about 1%, from about 0.1% to about 2.5%, from about 0.1% to about 5%, from about 0.1% to about 7.5%, from about 0.1% to about 10%, from about 0.1% to about 12.5%, from about 0.1% to about 15%, from about 0.1% to about 17.5%, from about 0.1% to about 20%, from about 0.1% to about 22.5%, from about 0.1% to about 25%, %, about 0.1% to about 30%, about 0.1% to about 40%, about 0.1% to about 50%, about 1% to about 2.5%, about 1% to about 5%, about 1% to about 7.5%, about 1% to about 10%, about 1% to about 12.5%, about 1% to about 15%, about 1% to about 17.5%, about 1% to about 20%, about 1% to about 22.5%, about 1% to about 25%, about 1% to about 30% , about 1% to about 40%, about 1% to about 50%, about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50 20% to about 50%, about 30% to about 40%, about 30% to about 50%, about 40% to about 50%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, about 90% to about 100%, about 10% to about 120%, about 10% to about 130%, about 10% to about 140%, about 10% to about 150%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 40%, about 15% to about 50%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 30% to about 40%, about 30% to about 50%, or about 40% to about 50% by weight.

3. The one or more therapeutic compounds are about 25 mg / mL to about 50 mg / mL, about 25 mg / mL to about 75 mg / mL, about 25 mg / mL to about 100 mg / mL, about 25 mg / mL to about 125 mg / mL, about 25 mg / mL to about 150 mg / mL, about 25 mg / mL ~about 200mg / mL, about 25mg / mL to about 250mg / mL, about 25mg / mL to about 300mg / mL, about 25mg / mL to about 350mg / mL, about 25mg / mL to about 400mg / mL, about 25mg / mL to about 450mg / mL, about 25mg / mL to about 500 mg / mL, about 25 mg / mL to about 550 mg / mL, about 25 mg / mL to about 600 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 150 mg / mL, about 50 mg / mL to about 200 mg / mL, about 50 mg / mL to about 250mg / mL, about 50mg / mL to about 300mg / mL, about 50mg / mL to about 350mg / mL, about 50mg / mL to about 4 00mg / mL, about 50mg / mL to about 450mg / mL, about 50mg / mL to about 500mg / mL, about 50mg / mL to about 55 0 mg / mL, about 50 mg / mL to about 600 mg / mL, about 75 mg / mL to about 100 mg / mL, about 75 mg / mL to about 150 mg / mL, about 75 mg / mL to about 200 mg / mL, about 75 mg / mL to about 250 mg / mL, about 75 mg / mL to about 300 mg / mL, about 75 mg / mL to about 350 mg / mL, about 75 mg / mL to about 400 mg / mL, about 75 mg / mL to about 450 mg / mL, about 75 mg / mL to about 500 mg / mL, about 75 mg / mL to about 550 mg / mL, about 75 mg / mL to about 600 m 3. The pharmaceutical composition of claim 1, wherein the amount of the glycerol in the pharmaceutical composition is about 100 mg / mL to about 150 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 250 mg / mL, about 100 mg / mL to about 300 mg / mL, about 100 mg / mL to about 350 mg / mL, about 100 mg / mL to about 400 mg / mL, about 100 mg / mL to about 450 mg / mL, about 100 mg / mL to about 500 mg / mL, about 100 mg / mL to about 550 mg / mL, or about 100 mg / mL to about 600 mg / mL.

4. The one or more glycerolipids are at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), at least 80% (by weight), at least 85% (by weight), at least 90% (by weight), or at 95% (by weight) and / or up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), up to 80% (by weight), up to 85% (by weight), up to 90% (by weight), up to 95% (by weight), or up to 99% (by weight) or from about 20% to about 30%, from about 20% to about 40%, from about 20% to about 50%, from about 20% to about 55%, from about 20% to about 60%, from about 20% to about 70%, from about 20% to about 80%, ...80%, from about 20% to about 90%, from about 20% to about 0% to about 90%, about 25% to about 30%, about 25% to about 40%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 70%, about 25% to about 80%, about 25% to about 90%, about 30% to about 40%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 40% to about 75%, about 40% to about 80%, about 40% to about 85%, about 40% to about 90%, about 40% to about 95%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 45% to about 75%, about 45% to about 80%, about 45% to about 85%, about 45% to about 90%, about 45% to about 95%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 50% to about 75%, about 50% to about 80%, about 50% to about 85%, about 50% to about 90%, about 50% to about 95%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 55% to about 75%, about 55% to about 80%, about 55% to about 85%,about 55% to about 90%, about 55% to about 95%, about 60% to about 65%, about 60% to about 70%, about 60% to about 75%, about 60% to about 80%, about 60% to about 85%, about 60% to about 90%, about 60% to about 95%, about 65% to about 70%, about 65% to about 75%, about 65% to about 80%, about 65% to about 85%, about 65% to about 90%, about 65% to about 95%, about 70% to about 75%, about 70% to about 80%, about 70% to about 85%, about 70 4. The pharmaceutical composition of any one of claims 1 to 3, wherein the amount of the active ingredient is from about 70% to about 95%, about 75% to about 80%, about 75% to about 85%, about 75% to about 90%, about 75% to about 95%, about 80% to about 85%, about 80% to about 90%, about 80% to about 95%, about 80% to about 99%, about 85% to about 90%, about 85% to about 95%, about 85% to about 99%, about 90% to about 95%, or about 90% to about 99% (by weight).

5. 5. The pharmaceutical composition of any one of claims 1 to 4, wherein the one or more glycerolipids comprise one or more hard fats, one or more liquid fats, or any combination thereof.

6. 6. The pharmaceutical composition of claim 5, wherein the one or more hard fats comprise one or more triglycerides.

7. The one or more hard fats are at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), and / or up to 10% (by weight), up to 15% (by weight) by weight), up to 20% by weight, up to 25% by weight, up to 30% by weight, up to 35% by weight, up to 40% by weight, up to 45% by weight, up to 50% by weight, up to 55% by weight, up to 60% by weight, up to 65% by weight, up to 70% by weight, up to 75% by weight, or from about 10% to about 20%, from about 10% to about 25%, from about 10% to about 30%, from about 10% to about 35%, from about 10% to about 40%, from about 10% to about 45%, from about 10% to about 50%, from about 10% to about 55%, from about 10% to about 60%, from about 10% to about 65% , about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% up to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40% , about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% up to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%,7. The pharmaceutical composition of claim 6, in an amount of about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70% by weight.

8. 8. The pharmaceutical composition of claim 5, wherein the one or more liquid fats comprise one or more partially hydrolyzed glycerolipids, one or more monoglycerides, or a combination thereof.

9. 9. The pharmaceutical composition of claim 8, wherein the one or more partially hydrolyzed glycerolipids comprises a mixture of mono-, di- and triglycerides.

10. The one or more partially hydrolyzed glycerolipids are at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), and / or up to 10% (by weight). , up to 15% (by weight), up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), or from about 10% to about 20%, from about 10% to about 25%, from about 10% to about 30%, from about 10% to about 35%, from about 10% to about 40%, from about 10% to about 45%, from about 10% to about 50%, from about 10% to about 55%, from about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%,10. The pharmaceutical composition of claim 8 or 9, in an amount of about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70% by weight.

11. The one or more monoglycerides are at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), and / or up to 10% (by weight), up to 15% (by weight), 5% (by weight), up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), or from about 10% to about 20%, from about 10% to about 25%, from about 10% to about 30%, from about 10% to about 35%, from about 10% to about 40%, from about 10% to about 45%, from about 10% to about 50%, from about 10% to about 55%, from about 10% to about 60%, from about 10% to about 25%, % to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 7 0%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%,9. The pharmaceutical composition of claim 8, in an amount of about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70% by weight.

12. 12. The pharmaceutical composition of any one of claims 5-11, wherein the one or more hard fats and the one or more liquid fats are in a hard fat to liquid fat ratio of about 5:1 to about 4:1, about 5:1 to about 3:1, about 5:1 to about 2:1, about 5:1 to about 1:1, about 4:1 to about 3:1, about 4:1 to about 2:1, about 4:1 to about 1:1, about 3:1 to about 2:1, about 3:1 to about 1:1, or about 2:1 to about 1:

1.

13. 12. The pharmaceutical composition of any one of claims 5 to 11, wherein the one or more hard fats and the one or more liquid fats are in a hard fat to liquid fat ratio of about 1:5 to about 1:4, about 1:5 to about 1:3, about 1:5 to about 1:2, about 1:5 to about 1:1, about 1:4 to about 1:3, about 1:4 to about 1:2, about 1:4 to about 1:1, about 1:3 to about 1:2, about 1:3 to about 1:1, or about 1:2 to about 1:

1.

14. The one or more digestive enhancers may be one or more bile acids, one or more phospholipids, one or more free C １４－２４ Fatty acid, one or more free C １４－２４ 14. The pharmaceutical composition of any one of claims 1 to 13, comprising a fatty acid surfactant, a tertiary glycerin surfactant, or any combination thereof.

15. The one or more digestive enhancers are at least 1% (by weight), at least 2.5% (by weight), at least 5% (by weight), at least 7.5% (by weight), at least 10% (by weight), at least 12.5% ​​(by weight), at least 15% (by weight), at least 17.5% (by weight), at least 20% (by weight), at least 22.5% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), at least 75% (by weight) and / or at most 1% (by weight), at most 2.5% (by weight), at most 5% (by weight), at most 7.5% (by weight), at most 10% (by weight), at most 12.5% ​​(by weight), at most 15% (by weight), at most 17.5% (by weight), at most 20% (by weight), at most 22.5% (by weight), at most 25% (by weight), at most 30% (by weight), at most 3 ... % (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), or up to 80% (by weight), or from about 1% to about 2.5% (by weight), from about 1% to about 5% (by weight), from about 1% to about 10% (by weight), from about 1% to about 15% (by weight), from about 1% to about 20% (by weight), from about 1% to about 25% (by weight), from about 2.5% to about 5% (by weight), from about 2.5% to about 10 % (by weight), about 2.5% to about 15% (by weight), about 2.5% to about 20% (by weight), about 2.5% to about 25% (by weight), about 5% to about 10% (by weight), about 5% to about 15% (by weight), about 5% to about 20% (by weight), about 5% to about 25% (by weight), about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 5 0%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%,about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35 % to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 40% to about 75%, about 40% to about 80%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 45% to about 75%, about 45% to 15. The pharmaceutical composition of claim 14, wherein the amount of the pharmaceutical composition is about 80%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 50% to about 75%, about 50% to about 80%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 55% to about 75%, about 55% to about 80%, about 60% to about 65%, about 60% to about 70%, about 60% to about 75%, about 60% to about 80%, about 65% to about 70% (by weight), about 65% to about 75%, about 65% to about 80%, about 70% to about 75%, about 70% to about 80%, or about 75% to about 80% (by weight).

16. 15. The pharmaceutical composition of claim 14, wherein the one or more bile acids comprise cholic acid, chenodeoxycholic acid, dafachronic acid, deoxycholic acid, glycocholic acid, glycohenodeoxycholic acid, lithocholic acid, taurochenodeoxycholic acid, taurocholic acid, any stereoisomers thereof, and any combination thereof.

17. The one or more bile acids are at least 0.1% (by weight), at least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), at least 10.0% (by weight), and / or at most 0.1% (by weight), at most 0.5% (by weight), at most 1.0% (by weight), at most 1.5% (by weight), at most 2.0% (by weight), at most 2.5% (by weight), at most 3.0% (by weight), at most 3.5% (by weight), at most 4.0% (by weight), at most 4.5% (by weight), at most 5.0% (by weight). , up to 5.5% (by weight), up to 6.0% (by weight), up to 6.5% (by weight), up to 7.0% (by weight), up to 7.5% (by weight), up to 8.0% (by weight), up to 8.5% (by weight), up to 9.0% (by weight), up to 9.5% (by weight), up to 10.0% (by weight), or from about 0.1% to about 0.5%, from about 0.1% to about 1.0%, from about 0.1% to about 2.0%, from about 0.1% to about 3.0%, from about 0.1% to about 4.0%, from about 0.1% to about 5.0%, from about 0.1% to about 6.0%, from about 0.1% to about 7.0%, from about 0.1% to about 8.0%, from about 0.1% to about 10.0% (by weight), About 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5.0%, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9. 0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%,about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% by weight.

18. The one or more free C １４－２４ At least 1% (by weight), at least 2.5% (by weight), at least 5% (by weight), at least 7.5% (by weight), at least 10% (by weight), at least 12.5% ​​(by weight), at least 15% (by weight), at least 17.5% (by weight), at least 20% (by weight), at least 22.5% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 50% (by weight), at least 60% (by weight) , at least 70% (by weight), at least 75% (by weight) and / or at most 1% (by weight), at most 2.5% (by weight), at most 5% (by weight), at most 7.5% (by weight), at most 10% (by weight), at most 12.5% ​​(by weight), at most 15% (by weight), at most 17.5% (by weight), at most 20% (by weight), at most 22.5% (by weight), at most 25% (by weight), at most 30% (by weight), at most 35% (by weight), at most 40% (by weight), at most 50% (by weight), at most 60% (by weight), at most 70% (by weight), at most 7 5% (by weight), or about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 10% (by weight), about 1% to about 15% (by weight), about 1% to about 20% (by weight), about 1% to about 25% (by weight), about 2.5% to about 5% (by weight), about 2.5% to about 10% (by weight), about 2.5% to about 15% (by weight), about 2.5% to about 20% (by weight), about 2.5% to about 25% (by weight), about 2.5% to about 30% (by weight), about 5% to about 10% (by weight), about 5% to about 15% (by weight), about 5% to about 20% (by weight), about 5% ~25% (by weight), approximately 5% to approximately 30% (by weight), approximately 10% to approximately 15% (by weight), approximately 10% to approximately 20% (by weight), approximately 10% to approximately 25% (by weight), approximately 10% to approximately 30% (by weight), approximately 10% to approximately 40% (by weight), approximately 10% to approximately 45% (by weight), approximately 1 0% to about 50% (by weight), about 10% to about 60% (by weight), about 10% to about 70% (by weight), about 15% to about 20% (by weight), about 15% to about 25% (by weight), about 15% to about 30% (by weight), about 15% to about 40% (by weight), about 15% to about 45% (by weight),About 15% to about 50% (by weight), about 15% to about 60% (by weight), about 15% to about 70% (by weight), about 20% to about 25% (by weight), about 20% to about 30% (by weight), about 20% to about 40% (by weight), about 20% to about 45% (by weight), about 2 0% to about 50% (by weight), about 20% to about 60% (by weight), about 20% to about 70% (by weight), about 30% to about 40% (by weight), about 30% to about 50% (by weight), about 30% to about 60% (by weight), about 30% to about 70% (by weight), about 30% 15. The pharmaceutical composition of claim 14, in an amount of about 35% to about 40% by weight, about 35% to about 50% by weight, about 35% to about 60% by weight, about 35% to about 70% by weight, about 35% to about 75% by weight, about 40% to about 50% by weight, about 40% to about 60% by weight, about 40% to about 70% by weight, about 40% to about 75% by weight, about 50% to about 60% by weight, about 50% to about 70% by weight, or about 60% to about 70% by weight.

19. The one or more free C １４－２４ At least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), at least 10.0% (by weight) and / or at most 0.1% (by weight), at most 0.5% (by weight), at most 1.0% (by weight), at most 1.5% (by weight), at most 2.0% (by weight), at most 2.5% (by weight), at most 3.0% (by weight), at most 3.5% (by weight), at most 4.0% (by weight), at most 4.5% (by weight), at most 5.0% (by weight), at most 5.5% (by weight), at most 6.0% (by weight), by weight), up to 6.5% by weight, up to 7.0% by weight, up to 7.5% by weight, up to 8.0% by weight, up to 8.5% by weight, up to 9.0% by weight, up to 9.5% by weight, up to 10.0% by weight or about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5 % to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5.0%, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2 0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%,about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% 15. The pharmaceutical composition of claim 14, in an amount of about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% by weight.

20. The pharmaceutical composition according to any one of claims 1 to 19, wherein the pharmaceutical composition is not an emulsion or a self-emulsifying formulation.

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