Precipitation inhibitor softgel formulations

Abstract

Described herein are precipitation inhibitor softgel capsule formulations, dosage forms, and methods for manufacturing and administration. In one embodiment, the precipitation inhibitor softgel capsules dissolve in about 2-10 minutes under laboratory conditions. Dosage forms comprising such capsules can prevent precipitation of BCS Class II active pharmaceutical ingredients when administered to subjects in need thereof.

Description

[0001] PRECIPITATION INHIBITOR SOFTGEL FORMULATIONS BACKGROUND Numerous researchers have investigated the use of polymeric precipitation inhibitors (PI) to maintain the supersaturation state of poorly soluble active pharmaceutical ingredients (APIs). This method is valuable for enhancing bioavailability by preventing or delaying API precipitation within the gastrointestinal tract. The suitability of precipitation inhibitors in oral dosage forms, especially soft capsules, is limited due to their poor solubility in commonly used excipients in the fill material. Even though precipitation inhibitor agents are typically soluble in hydrophilic co-solvents such as (poly)alkylene glycol, (poly)alkylene glycol alkyl ether, or alcohol, they have a low solubility in lipid excipients like oils, e.g., fatty acid ester of glycerol or derivative thereof, polar oils, e.g., fatty acid mono-diester of glycerol or propylene glycol or derivative thereof, water-insoluble surfactants having a hydrophilic-lipophilic balance (HLB) of less than 11, e.g., phospholipids, sorbitan fatty acid ester, propylene glycol fatty acid ester, glycerol fatty acid ester, or polyoxylglyceride, and water-soluble surfactants having an HLB of 11 or greater, e.g., polyoxyl castor oil, polyoxyl hydrogenated castor oil, polyoxyl sorbitan fatty acid ester, polyoxyl tocopherol ester derivatives, or polyoxylglyceride. This limitation restricts their application for APIs with low aqueous solubility and / or permeability since they usually need the adoption of advanced techniques like Self-Emulsifying Drug Delivery Systems (SEDDS), which make use of the above-mentioned excipients. The combination of precipitation inhibitors with SEDDS formulations represents a state- of-the-art approach, known as Supersaturable Self-Emulsifying Drug Delivery Systems (Su- SEDDS). This approach has demonstrated effectiveness in enhancing bioavailability and reducing variability in in vivo drug precipitation. Su-SEDDS may have been applied in solid dosage forms, including powders, granules, tablets, suppositories, implants, or related formulations. Liquid Su-SEDDS formulations face limitations with soft or hard capsules, primarily due to physical incompatibility issues. There is a need for capsule formulations that incorporate various precipitation inhibitors into the softgel capsule shell. SUMMARY One embodiment described herein is a precipitation inhibitor softgel capsule formulation, the formulation comprising: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. In one aspect, the one or more film-forming polymers comprises gelatin, gelatin hydrolysates, collagen, carrageenans, or agars. In another aspect, the one or more film-forming polymers comprises gelatin having a Bloom value of about 50 Bloom to about 300 Bloom. In another aspect, the gelatin has a Bloom value of about 150 Bloom. In another aspect, the formulation comprises about 20–40% by mass of the one or more film-forming polymers. In another aspect, the one or more precipitation inhibitors comprise one or more of polyvinylpyrrolidone, polyvinyl acetate phthalate, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer, poloxamers, polymethylmethacrylates, cellulose acetate phthalate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, derivatives thereof, or combinations thereof. In another aspect, the formulation comprises about 0.1–10% by mass of the one or more precipitation inhibitors. In another aspect, the formulation comprises about 1–8% by mass of the one or more precipitation inhibitors. In another aspect, the formulation comprises about 2.5–5% by mass of the one or more precipitation inhibitors. In another aspect, the one or more plasticizers or co-solvents comprises solutions of polyols, monosaccharides, disaccharides, oligosaccharides, blended hydrophilic molecules, glycerol, sorbitol, polyethylene glycols, or maltitol. In another aspect, the formulation comprises about 10–20% by mass of the one or more plasticizers or co-solvents. In another aspect, the one or more neutralization agents comprises NH4OH, NaOH, KOH, or combinations thereof. In another aspect, the formulation comprises about 0.1–0.5% by mass of the one or more neutralization agents. In another aspect, the one or more solvents comprises water. In another aspect, the formulation further comprises one or more of colorants, opacifiers, flavors or sweeteners, humectants, preservatives, coatings, viscosity modifiers, fillers or bulking agents, active pharmaceutical ingredients, or buffering salts and acids. In another aspect, the formulation comprises about 0.01–10% by mass of one or more colorants comprising synthetic dyes, natural dyes, or a combination thereof. In another aspect, the formulation comprises about 0.01–1% by mass of one or more opacifiers comprising titanium dioxide, zinc oxide, iron oxide, calcium carbonate, or combinations thereof. In another aspect, the formulation comprises about 0.01–1% by mass of one or more flavors or sweeteners. In another aspect, the capsule immediately releases at 37 °C at pH 1.2–7 and delivers the precipitation inhibitor into the medium. In another aspect, the capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7. Another embodiment described herein is a method for manufacturing a precipitation inhibitor softgel capsule, the method comprising: (a) preparing a gel mass composition comprising one or more film-forming polymers, one or more precipitation inhibitors, one or more plasticizers or co-solvents, and one or more solvents to form a gel mass; (b) heating the gel mass to create a homogenous and de-aerated gel mass; optionally, one or more antifoaming agents may be incorporated to suppress foam during the preparation of the gels. (c) ageing the homogenous and de-aerated gel mass to create an aged gel mass; (d) casting the aged gel mass into films or ribbons using heat-controlled drums or surfaces; (e) transferring a homogenized fill solution to an encapsulation line; (f) encapsulating the homogenized fill solution within the gel mass films or ribbons using rotary dye encapsulation to create a capsule; (g) drying and finishing the capsule; (h) optionally, printing identification on the capsule; (i) optionally, coating the capsule with a coating and drying; and (j) post processing and packaging. In another aspect, the gel mass comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. In another aspect, heating the gel mass in step (b) comprises a temperature of about 57–80 °C under vacuum for about 15–30 minutes to create the homogenous and de-aerated gel mass. In another aspect, ageing the homogenous and de-aerated gel mass in step (c) comprises a temperature of about 50–60 °C for about 12–96 hours to create the aged gel mass. A precipitation inhibitor softgel capsule manufactured by the methods described herein. Another embodiment described herein is a pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7 and releases the precipitation inhibitor and the one or more B BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250. In one aspect, the precipitation inhibitor softgel capsule comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. Another embodiment described herein is a method for administering one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to a subject in need thereof, the method comprising administering to the subject a pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising the one or more BCS Class II APIs, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes following administration and releases the precipitation inhibitor and the matrix fill comprising the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to the subject, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250. In one aspect, the precipitation inhibitor softgel capsule comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. DESCRIPTION OF THE DRAWINGS FIG.1A–B shows the results of rheological properties of the precipitation inhibitor softgel capsule gel masses. FIG. 1A shows the viscosity of the gel masses containing precipitation inhibitors at 56 °C. FIG.1B shows the gel strength of the gel masses containing precipitation inhibitors at 15 °C. FIG.2 shows the results of gel swatch disintegrations performed in 50 mL of 0.1 M HCl (pH ~ 1) at 37 °C for 30 min with 2.5 and 5% by mass precipitation inhibitors. The control was a typical soft gel mass without precipitation inhibitor. DETAILED DESCRIPTION Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. For example, any nomenclatures used in connection with, and techniques of pharmaceutical formulation, medicinal chemistry, biochemistry, molecular biology, immunology, microbiology, genetics, cell and tissue culture, and protein and nucleic acid chemistry described herein are well known and commonly used in the art. In case of conflict, the present disclosure, including definitions, will control. Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the embodiments and aspects described herein. As used herein, the terms such as “include,” “including,” “contain,” “containing,” “having,” and the like mean “comprising.” The present disclosure also contemplates other embodiments “comprising,” “consisting essentially of,” and “consisting of” the embodiments or elements presented herein, whether explicitly set forth or not. As used herein, the term “a,” “an,” “the” and similar terms used in the context of the disclosure (especially in the context of the claims) are to be construed to cover both the singular and plural unless otherwise indicated herein or clearly contradicted by the context. In addition, “a,” “an,” or “the” means “one or more” unless otherwise specified. As used herein, the term “or” can be conjunctive or disjunctive. As used herein, the term “and / or” refers to both the conjunctive and disjunctive. As used herein, the term “substantially” means to a great or significant extent, but not completely. As used herein, the term “about” or “approximately” as applied to one or more values of interest, refers to a value that is similar to a stated reference value, or within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, such as the limitations of the measurement system. In one aspect, the term “about” refers to any values, including both integers and fractional components that are within a variation of up to ± 10% of the value modified by the term “about.” Alternatively, “about” can mean within 3 or more standard deviations, per the practice in the art. Alternatively, such as with respect to biological systems or processes, the term “about” can mean within an order of magnitude, in some embodiments within 5-fold, and in some embodiments within 2-fold, of a value. As used herein, the symbol “~” means “about” or “approximately.” All ranges disclosed herein include both points as discrete values as well as all integers and fractions specified within the range. For example, a range of 0.1–2.0 includes 0.1, 0.2, 0.3, 0.4...2.0. If the end points are modified by the term “about,” the range specified is expanded by a variation of up to ±10% of any value within the range or within 3 or more standard deviations, including the end points. As used herein, the terms “control,” or “reference” are used herein interchangeably. A “reference” or “control” level may be a predetermined value or range, which is employed as a baseline or benchmark against which to assess a measured result. “Control” also refers to control experiments or control cells. As used herein, “treatment” or “treating” refers to prophylaxis of, preventing, suppressing, repressing, reversing, alleviating, ameliorating, or inhibiting the progress of biological process including a disorder or disease, or completely eliminating a disease. A treatment may be either performed in an acute or chronic way. The term “treatment” also refers to reducing the severity of a disease or symptoms associated with such disease prior to affliction with the disease. “Repressing” or “ameliorating” a disease, disorder, or the symptoms thereof involves administering a cell, composition, or compound described herein to a subject after clinical appearance of such disease, disorder, or its symptoms. “Prophylaxis of” or “preventing” a disease, disorder, or the symptoms thereof involves administering a cell, composition, or compound described herein to a subject prior to onset of the disease, disorder, or the symptoms thereof. “Suppressing” a disease or disorder involves administering a cell, composition, or compound described herein to a subject after induction of the disease or disorder thereof but before its clinical appearance or symptoms thereof have manifest. As used herein, the term “prophylaxis” refers to preventing or reducing the progression of a disorder, either to a statistically significant degree or to a degree detectable by a person of ordinary skill in the art. As used herein, the terms “effective amount” or “therapeutically effective amount,” refers to a substantially non-toxic, but sufficient amount of an action, agent, composition, or cell(s) being administered to a subject that will prevent, treat, or ameliorate to some extent one or more of the symptoms of the disease or condition being experienced or that the subject is susceptible to contracting. The result can be the reduction or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. An effective amount may be based on factors individual to each subject, including, but not limited to, the subject’s age, size, type or extent of disease, stage of the disease, route of administration, the type or extent of supplemental therapy used, ongoing disease process, and type of treatment desired. As used herein, the terms “inhibit,” “inhibition,” or “inhibiting” refer to the reduction or suppression of a process, condition, symptom, disorder, or disease, or a significant decrease in the activity of a process. In one aspect, the term “inhibitor” refers to one or more compounds that inhibits, retards, or prevents precipitation or crystallization of an API in an aqueous environment. See “precipitation inhibitor” below. As used herein, the term “subject” refers to an animal. Typically, the subject is a mammal. A subject also refers to primates (e.g., humans, male or female; infant, adolescent, or adult), non- human primates, rats, mice, rabbits, pigs, cows, sheep, goats, horses, dogs, cats, fish, birds, and the like. In one embodiment, the subject is a primate. In one embodiment, the subject is a human. As used herein, a subject is “in need of treatment” if such subject would benefit biologically, medically, or in quality of life from such treatment. A subject in need of treatment does not necessarily present symptoms, particularly in the case of preventative or prophylaxis treatments. As used herein, the term “active ingredient” or “active pharmaceutical ingredient” or “active pharmaceutical agent” or “API” or “drug” refers to an agent, active ingredient, compound, or substance, compositions, or mixtures thereof, that provide a pharmacological, often beneficial, effect. Reference to a specific active ingredient includes, where appropriate, the active ingredient and any of its pharmaceutically acceptable salts or esters. In some embodiments, one or more active pharmaceutical ingredients may be incorporated into a matrix fill as described herein. In some embodiments, one or more active pharmaceutical ingredients may be incorporated into a pressed tablet as described herein. In some embodiments, one or more active pharmaceutical ingredients may be incorporated into a softgel capsule formulation as described herein. As used herein, the Biopharmaceutics Classification System (BCS) is a system to differentiate APIs based on their solubility and permeability. An API is considered highly soluble when the highest dose strength is soluble in 250 mL or less of aqueous media over the pH range of 1 to 7.5. The volume estimate of 250 mL is derived from typical bioequivalence study protocols that prescribe administration of a drug product to fasting human volunteers with a glass of water. An API is considered highly permeable when the extent of absorption in humans is determined to be 90% or more of the administered dose based on a mass-balance determination or in comparison to an intravenous dose. There are four BCS classifications, BCS I, BCS II, BCS III, and BCS IV. BCS Class I APIs have high permeability and high solubility. These APIs are highly absorbed. BCS Class II APIs have high permeability and low solubility. The bioavailability of BCS Class II APIs is dependent on their solubility. BCS Class III APIs have low permeability and high solubility. BCS Class III APIs solvate rapidly and the absorption rate of is dependent on the permeation rate. BCS Class IV APIs have low permeability and low solubility and consequently low bioavailability. The terms “dosage” or “dose” denote any form of the active ingredient formulation or composition that contains an amount sufficient to initiate or produce a therapeutic effect with at least one or more administrations. The dosage form used herein is for oral administration. The preferred oral dosage forms are soft capsules. As used herein, the term “pharmaceutical composition” refers to a composition comprising at least one active ingredient, nutraceutical, nutritional, or vitamin. In some embodiments described herein, a pharmaceutical composition comprises a soft capsule shell having been formed into a capsule, for example, using rotary die encapsulation comprising one or more polyunsaturated fatty acids, optionally with one or more vitamins, antioxidants, or other active ingredients. As used herein, the term “formulation” or “composition” refers to the active pharmaceutical ingredient or drug in combination with pharmaceutically acceptable excipients. This includes orally administrable formulations as well as formulations administrable by other means. “Formulation” and “composition” are used interchangeably herein. As used herein, the terms “room temperature,” “RT,” or “ambient temperature” refer to the typical temperature in an indoor laboratory setting. In one aspect, the laboratory setting is climate controlled to maintain the temperature at a substantially uniform temperature or with a specific range of temperatures. In one aspect, “room temperature” refers a temperature of about 15–30 °C, including all integers and endpoints within the specified range. In another aspect, “room temperature” refers a temperature of about 15–30 °C; about 20–30 °C; about 22–30 °C; about 25–30 °C; about 27–30 °C; about 15–22 °C; about 15–25 °C; about 15–27 °C; about 20–22 °C; about 20–25 °C; about 20–27 °C; about 22–25 °C; about 22–27 °C; about 25–27 °C; about 15 °C ± 10%; about 20 °C ± 10%; about 22 °C ± 10%; about 25 °C ± 10%; about 27 °C ± 10%; ~20 °C, ~22 °C, ~25 °C, or ~27 °C, at standard atmospheric pressure. As used herein, the terms “mass percent,” “percent mass,” “weight percent,” or “% wt,” refer to the mass of a specific component of a composition as a percentage of the total mass of the composition (assumed to be 100%). The terms “percent (or %) ... wet mass” refers to the mass percentage of a composition that contains a mass of solvent, typically water, in the composition. Likewise, “percent (or %) . . . dry mass” refers to the mass percentage of a composition containing only or predominately dry ingredients. As used herein, the term “wet shell mass,” or “wet capsule mass” refer to the mass of the capsule during formulation and manufacturing but before drying. During the manufacturing process, softgel capsules are dried and a portion of the solvent (typically water) evaporates. This increases the integrity and rigidity of the capsule shell. Consequently, the relative mass percentage of the non-fugative components increases proportionate to the decrease in the amount of solvent that has evaporated during drying. It is difficult to measure the “dry shell mass” or “dry shell mass percentage,” but these values can be estimated based on the difference in mass of the capsule immediately after manufacturing and after drying, assuming that the difference in mass is solely due to solvent evaporation. As used herein, the terms “release” or “releasing” refer to the discharge of a portion of the active ingredient from a softgel matrix into a medium, such as a buffer or stomach fluid. As used herein, the terms “rapid release” or “rapid releasing” refer to a softgel capsule that rapidly releases a portion of the active ingredient from a softgel matrix fill into a medium as compared to a typical softgel capsule. In one aspect, “rapid releasing” refers to a softgel capsule that rapidly releases a portion of the active ingredient from the matrix fill into the medium within about 0.5 min, 1 minute, 2 min, 3 min, 4 min, 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 15 min, 20 min, or 30 min. A used herein, the term “rupture” refers to the initial opening of a softgel capsule where the contents begin to release from the matrix and dissolve into the medium. As used herein, the terms “rapid rupture” or “rapid rupturing” refer to a softgel capsule that rapidly ruptures in a medium as compared to a standard soft gel capsule. In one aspect, “rapid rupturing” refers to a softgel capsule that rapidly releases a portion of the active ingredient from the matrix fill into the medium within about 0.5 min, 1 minute, 2 min, 3 min, 4 min, 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 15 min, 20 min, or 30 min. One embodiment described herein is a rapid rupturing soft capsule. As used herein, the term “dissolution” refers to the solvation of a softgel capsule. Without being bound by any theory, a softgel capsule shell begins slowly dissolving upon entering a medium such as a buffer or stomach fluid. As the capsule shell dissolves, the capsule typically ruptures at a point of weakness, such as a manufacturing seam. The capsule matrix begins to release the fill from the initial rupture opening while the medium enters the rupture and begins solvating the matrix remaining in the capsule. Simultaneously, the capsule shell continues to dissolve, and the rupture opening grows in size, while the matrix is released. Over a period of time, both the matrix and capsule shell are completely solvated, and the capsule is dissolved. As used herein, the terms “rapid dissolution” or “rapid dissolving” refer to a softgel capsule that rapidly dissolves in a medium as compared to a standard soft gel capsule. In one aspect, “rapid dissolving” refers to a softgel capsule that rapidly dissolves within about 0.5 min, 1 min, 2 min, 3 min, 4 min, 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min, 55 min, or 60 min. As used herein, the terms “typical softgel capsule” or “standard softgel capsule” refer to a softgel capsule having a shell that contains one or more film forming polymers (e.g., gelatin), a plasticizer (e.g., glycerol), and water and that is manufactured by rotary die encapsulation. Typical softgel capsules do not contain precipitation inhibitors as described herein. Typical softgel capsules containing an aqueous (non-oil) fill generally rupture in a buffer medium within 15–20 minutes and completely dissolve within 30–45 min. As used herein, rupture testing, dissolution testing, comparative dissolution, and similar experiments are conducted in compliance with and according to protocols established by ICH Q4B Annex 5 and Annex 7 (EMA / CHMP / ICH / 308895 / 2008 and EMA / CHMP / ICH / 645469 / 2008) and the United States Pharmacopeia (USP), including USP Disintegration Method 〈701〉 and USP General Chapter 〈2040〉, each of which are incorporated by reference herein for such teachings. Specific apparatus are described in USP General Chapter 〈711〉 Dissolution and consists of Apparatus I – Basket Apparatus; Method II – Paddle Apparatus; Method III – Reciprocating Cylinder; and Method IV – Flow-Through Cell. See USP General Chapter 〈711〉 DISSOLUTION, Stage 6 Harmonization, The United States Pharmacopeial Convention (2011), which is incorporated by reference herein for such teachings. As used herein, the term “film-forming polymer” refers to a water-soluble polymer agent capable of forming a film that enhances the integrity of a softgel capsule shell. Typical film forming polymers are gelatin, gelatin hydrolysates, collagen, or the like. As used herein, the term “plasticizer” refers to an agent that adds extensibility, dispensability, flexibility, elasticity, rigidity, pliability, and / or enhanced mechanical properties to a softgel capsule shell by interacting with the film-forming polymer. The plasticizer can minimize brittleness and cracking of the softgel capsule shell. As used herein, the term “co-solvent” refers to an agent that aids in the solubility of a softgel capsule. As used herein, the term “precipitation inhibitor,” “precipitation inhibitor agent,” or “polymeric precipitation inhibitor” refers to a compound that inhibits, retards, or prevents precipitation of an API in an aqueous environment (in vitro or in vivo), thereby maintaining the API’s solubility in the aqueous environment. In one embodiment, precipitation inhibitors are incorporated into a softgel capsule shell encapsulating a BCS Class II API formulation in the capsule matrix. Upon dissolution of the capsule shell, the API formulation is released and the precipitation inhibitor is available in the environment to prevent precipitation of the API. Exemplary precipitation inhibitors comprise polyvinylpyrrolidone (PVP), polyvinyl acetate phthalate, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer, poloxamers, hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose, cellulose acetate phthalate, derivatives thereof, or combinations thereof. As used herein, the term “solvent” refers to an aqueous agent used to solubilize the various components of a softgel capsule formulation. As used herein, the term “Cmax” as used herein refers to the maximum observed blood (plasma, serum, or whole blood) concentration or the maximum blood concentration calculated or estimated from a concentration to time curve and is expressed in units of mg / L or ng / mL, as applicable. As used herein, the term “Cmin” refers to the minimum observed blood (plasma, serum, or whole blood) concentration or the minimum blood concentration calculated or estimated from a concentration to time curve and is expressed in units of mg / L or ng / mL, as applicable. As used herein, the term “Cavg” refers to the blood (plasma, serum, or whole blood) concentration of the drug within the dosing interval, is calculated as AUC / dosing interval, and is expressed in units of mg / L or ng / mL, as applicable. As used herein, the term “Tmax” refers to the time after administration at which Cmaxoccurs and is expressed in units of hours (h) or minutes (min), as applicable. As used herein, the term “AUC0→τ” refers to area under the blood (plasma, serum, or whole blood) concentration versus time curve from time zero to time tau (τ) over a dosing interval at steady state, where tau is the length of the dosing interval, and is expressed in units of h·mg / L or h·ng / mL, as applicable. For example, the term AUC0→12as used herein refers to the area under the concentration versus time curve from 0 to 12 hours. As used herein, the term “AUC0→∞” refers to the area under the blood (plasma, serum, or whole blood) concentration versus time curve from time 0 hours to infinity and is expressed in units of h·mg / L or h·ng / mL, as As used herein, the term “AUCoverall” refers to the combined area under the blood (plasma, serum, or whole blood) concentration versus time curve, and is expressed in units of h·mg / L (or h·ng / mL) for at least one or more doses of the pharmaceutical compositions described herein. In one aspect, the “AUCoverall” refers to the combined area under the blood concentration versus time curve for at least two doses of the pharmaceutical compositions described herein. Described herein are softgel capsule formulations that comprise precipitation inhibitors such as polyvinylpyrrolidones, celluloses, or tri-block-co-polymers incorporated into the capsule shell. These formulations overcome compatibility issues between precipitation inhibitors and oil- based capsule fills; precipitation inhibitors are typically insoluble in oil based fills such as those used in Self-Emulsifying Drug Delivery Systems (SEDDS). These solubility challenges can be overcome by the incorporation of precipitation inhibitors in the capsule shell composition. This approach eliminates the need for precipitation inhibitor solubilization within oil-based capsule fills such as with SEDDS. Precipitation inhibitor agents are readily soluble in aqueous or polar solutions such as water, glycerol, and sorbitol, which are commonly used for the preparation of soft capsule shells. However, a challenge is the formulation of soft gel capsules comprising precipitation inhibitors that do not adversely affect the shell integrity or elasticity and still remain compatible with rotary-die encapsulation manufacturing. Described herein, are precipitation inhibitor soft gel capsules (“PrecInGel”). In one embodiment, the precipitation inhibitor soft gel capsules comprise one or more film forming polymers, one or more precipitation inhibitors, one or more plasticizers, one or more solvents, optionally one or more alkali-neutralizing agents, optionally one or more colorants, optionally, one or more opacifiers, optionally one or more flavoring agents, that have suitable physical properties for soft capsule applications. In one aspect, the precipitation inhibitor soft gel capsules comprise one or more film forming polymers, one or more precipitation inhibitors, one or more plasticizers, and one or more solvents. It is understood that the softgel capsule formulations, precipitation inhibitor softgel capsules, or any other formulation described herein maintain the supersaturation state of APIs, preventing crystallization and ensuring that the APIs remain dissolved and absorbable in the gastrointestinal tract. This significantly enhances the bioavailability and therapeutic efficacy of APIs. Capsule Compositions One embodiment described herein is a formulation for a precipitation inhibitor softgel capsule. An exemplary precipitation inhibitor capsule composition is shown in Table 1. In one embodiment, the precipitation inhibitor softgel capsule has the composition of Table 1, including all possible combinations of the specified ranges that collectively constitute 100% of the total weight percentage. This includes options with or without the inclusion of optional excipients, opacifiers, solvents, colorants, and flavorings. Table 1: Exemplary Precipitation Inhibitor Capsule Shell Components Component Function Exemplary ComponentsMass Range(%)Gelatin, gelatin Film-forming polymers Capsule Shell hydrolysates, collagen, 15–45 carrageenan, agars polyvinylpyrrolidones, poloxamers, polyvinyl caprolactam-polyvinyl Inhibit precipitatioacetate-polyethylene Precipitation Inhibitorsnof APIglycol graft co-polymers, 0.01–20% hydroxypropyl- methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose Extensibility, Polyols, Dispensability, monosaccharides, dis Plasticizers Flexibility, accharides, Elasticity, Rigidity oligosaccharides, blended 5–30 and Mechanical hydrophilic molecules, Properties glycerol, sorbitol, polyethylene glycols Alkali-neutralizing NH OH (30%), NaOH agent (optional)Adjust pH4, KOH, triethylamine0.01–2Cosolvents (optional) Aids solubilityMaltitol (hydrogenatedglucose syrup; Lycasin®) 5–2510–45 Water Solvent Purified water (q.s. to reach 100%) Colorant (optional) Color shellNatural and syntheticFD&C colors 0.01–2Opacifiers (optional) Opacify shellTitanium dioxide, IronOxide 0.01–7.5Flavorants (optional) Flavor shellOrange, grape, cherry,sweeteners, etc. 0.01–2dimethicone, silicone oil, Anti-foaming agents Prevent foaming / simethicone, (optional) Aids process polydimethylsiloxane, 0.1-1.0 polyethylene glycol, propylene glycol alginate Total Shell Mass Percentage (%) 100 Theoretical Total Shell Weight (Dry shell) 1–3000 mg Film Forming Polymers Examples of film-forming polymers that are useful for creating soft capsules as described herein comprise gelatins, including acid bone gelatin, lime bone gelatin, beef skin gelatin, pig skin gelatin, chicken skin gelatin, fish gelatin, acid hide gelatin, gelatin hydrolysate, collagens, or combinations thereof. The gelatin can be Type A or Type B gelatin. Type A gelatin is derived from the acid hydrolysis of collagen (e.g., acid bone gelatin or pig skin gelatin), while Type B gelatin (e.g., lime bone gelatin) is derived from the alkaline hydrolysis of collagen. Traditionally, bovine bones and skins are used as raw materials for manufacturing Type A and Type B gelatin, while porcine skins are used extensively for manufacturing Type A gelatin. In addition, at neutral pH values, Type A gelatins (acid processed gelatins) are typically net cationic (e.g., isoelectric point of about 7–9) and Type B gelatins (alkali processed gelatins) are typically net anionic (e.g., isoelectric point of about 4.5–5.3). Type A gelatin typically has higher plasticity and elasticity than type B gelatin; type B gelatin typically has higher gel strength than type A gelatin. The strength of gelatin compositions is typically defined by their Bloom strength or grade. The Bloom test determines the weight (in grams) needed by a 0.5-inch diameter probe to deflect the surface of a gel 4 mm without breaking it. The result is expressed as “Bloom” or “Bloom strength.” The soft capsules described herein utilize gelatins with Bloom strengths in the range of about 20 Bloom to about 400 Bloom, including each integer within the specified range. In one embodiment, Bloom strengths for soft capsules described herein are about 30 Bloom to about 250 Bloom including each integer within the specified range. In some embodiments, the gelatin Bloom strength is about 30 Bloom, about 50 Bloom, about 80 Bloom, about 100 Bloom, about 120 Bloom, about 150 Bloom, about 180 Bloom, about 200 Bloom, about 250 Bloom, about 300 Bloom, about 350 Bloom, or about 400 Bloom. In one embodiment, the gelatin Bloom strength is 100 Bloom. In another embodiment, the gelatin Bloom strength is 150 Bloom. In another embodiment, the gelatin Bloom strength is 175 Bloom. In another embodiment, the gelatin Bloom strength is 200 Bloom. In another embodiment, the gelatin Bloom strength is 140–160 Bloom. Examples of film-forming polymers that are useful for creating non-animal / non-gelatin soft capsules described herein are kappa carrageenan, iota carrageenan, lambda carrageenan, or combinations thereof. Examples of film-forming anionic polysaccharides, as described herein, comprise polygalacturonic acid, carboxymethyl pullulan, carboxymethyl cellulose, hyaluronic acid, cellulose phthalate, cellulose succinate, alginate, sodium alginate, and pectin, acrylic and methacrylate acid copolymers, cellulose acetate phthalate (CAP), cellulose acetate butyrate, hydroxypropylmethylcellulose phthalate (HPMCP), algenic acid salts such as sodium or potassium alginate, or shellac. Poly(methacylic acid-co-methyl methacrylate) anionic copolymers based on methacrylic acid and methyl methacrylate are particularly stable and are preferred in some embodiments. Poly(meth)acrylates (methacrylic acid copolymer), available under the trade name EUDRAGIT®(Evonik Industries AG, Essen, Germany), are provided as powder or aqueous dispersions. In one aspect, the methacrylic acid copolymer can be EUDRAGIT®L 30 D-55; EUDRAGIT®L 100-55; EUDRAGIT®L 100; EUDRAGIT®L 12.5; EUDRAGIT®S 100; EUDRAGIT®S 12.5; EUDRAGIT®FS 30 D; EUDRAGIT®E 100; EUDRAGIT®E 12.5; EUDRAGIT®E PO; EUDRAGIT®RL 100; EUDRAGIT®RL PO; EUDRAGIT®RL 30 D; EUDRAGIT®RL 12.5; EUDRAGIT®RS 100; EUDRAGIT®RS PO; EUDRAGIT®RS 30 D; EUDRAGIT®RS 12.5; EUDRAGIT®NE 30 D; EUDRAGIT®NE 40 D; EUDRAGIT®NM 30 D; or other poly(meth)acrylate polymers. Film-forming polymers typically comprise a mass percentage of about 15–60% of the total wet mass of a shell, including each integer and fraction within the specified range. For example, one or more film-forming polymers may comprise a mass percentage of about 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60%, or about 15–20%, 15–25%, 15–30%, 15–35%, 15– 40%, 15–45%, 15–50%, 15–55%, 20–25%, 20–30%, 20–35%, 20–40%, 20–45%, 20–50%, 20– 55%, 20–60%, 25–30%, 25–35%, 25–45%, 25–50%, 25–55%, 25–60%, 30–35%, 30–40%, 30– 45%, 30–50%, 30–55%, 30–60%, 35–40%, 35–45%, 35–50%, 35–55%, 35–60%, 40–45%, 40– 50%, 40–55%, 40–60%, 45–50%, 45–55%, 45–60%, 50–55%, 50–60%, or 55–60% of the total wet mass of a shell, including each integer and fraction within these specified values and ranges. In some embodiments, one or more film-forming polymers may comprise a mass percentage of about 20–40% of the total wet mass of a shell, including each integer and fraction within this specified range. In one non-limiting embodiment, one or more film-forming polymers may comprise a mass percentage of about 35–45%, or about 35–40%, of the total wet mass of a shell, including each integer and fraction within these specified ranges. Precipitation Inhibitors (PI) Precipitation inhibitors can prevent or retard the nucleation of APIs. This can be done thermodynamically by increasing the solubility of the API, e.g., using surfactants, or kinetically by interaction of polymeric precipitation inhibitors with the API. The mechanisms of kinetic inhibition by polymeric precipitation inhibitors consist of hydrogen bonding and hydrophobic interactions. Hydrogen bonds between the precipitation inhibitor and the API increase the nucleation activation energy. Hydrophobic interactions between the precipitation inhibitor and a precipitated crystal of an API prevent crystal growth due to steric hindrance of the precipitation inhibitor, which forms a protective layer around the crystal from the aqueous environment to prevent further crystal growth. Here, hydrophilic polymeric precipitation finhibitors are explored which mainly exhibit kinetic inhibition. Other important factors are the molecular weight and the rigidity of the polymeric precipitation inhibitors in their kinetic inhibition behavior. The molecular weight of the polymer correlates with the number of functional groups that can interact with the API. Furthermore, the rigidity of the polymer is directly related to the extent of its interaction with the surface of the API, since a flexible polymer can form loops that do not interact with the API. For example, in one embodiment, the precipitation inhibitor can be polyvinylpyrrolidone, e.g., poly(1-vinyl-2- pyrrolidone) (PVP), polyvinyl acetate phthalate (PVAP), polyvinylpyrrolidone-vinyl acetate copolymer (PVP-VA), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co- polymer, poloxamers (nonionic triblock copolymers of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene; Pluronic™, Kolliphor™), polymethylmethacrylates (Eudragits®), cellulose acetate phthalate (CAP), carboxymethyl ethylcellulose (CMEC), hydroxypropyl methylcellulose (hypromellose, HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose phthalate (HPMCP), hydroxyethylcellulose (HEC), hydroxymethylcellulose (HMC), hydroxypropylcellulose (HPC), derivatives thereof, or combinations thereof. In one embodiment, the precipitation inhibitors comprise polyvinylpyrrolidone (e.g., poly(1- vinyl-2-pyrrolidone)) with molecular weights ranging from 2,000 to 1,200,000 Da, poloxamers with a molecular weight between 10,000–14,600 Da, polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft co-polymer with a molecular weigh between 90,000 and 140,000 Da, hydroxypropyl methylcellulose (HPMC) with a hydroxypropyl content between 1–35%, and a methoxy content between 15–35%, hydroxypropylcellulose (HPC) with a molecular weight of 95,000 Da, hydroxyethylcellulose (HEC) with a molecular of 90,000 Da, methylcellulose (HMC), or combinations thereof. The mass percentages of the one or more precipitation inhibitors in the gel mass comprise about 0.01–20% including the end points and all integers and subranges within the specified range. In one aspect, the one or more precipitation inhibitors comprise about 0.01%, 0.05%, 0.1%, 0.5%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% by mass of the gel mass. In one embodiment described herein, the precipitation inhibitor comprises 0.01–10% of polyvinylpyrrolidone with a molecular weight of about 2–3 kDa (e.g., Kollidon® 12PF). In another embodiment described herein, the precipitation inhibitor comprises 0.01–10% of polyvinylpyridine with a molecular weight of about 44–54 kDa (e.g., Kollidon® 30). In another embodiment described herein, the precipitation inhibitor comprises 0.01–10% of polyvinylpyridine with a molecular weight of about 900–1,200 kDa (e.g., Kollidon® 90F). In another embodiment described herein, the precipitation inhibitor comprises 0.01–10% of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer with a molecular weight between 90–140 kDa (e.g., Soluplus®). In another embodiment described herein, the precipitation inhibitor comprises 0.01–10% of poloxamer with a molecular weight of about 10–14.6 kDa (e.g., Kolliphor® P 407 Geismar). In another embodiment described herein, the precipitation inhibitor comprises 0.01–10% of hydroxypropylcellulose with a molecular weight of about 95 kDa (e.g., Klucel™ LF PH). In another embodiment described herein, the precipitation inhibitor comprises 0.01–10% of hydroxyethylcellulose with a molecular weight of about 90 kDa (e.g., Natrosol™ 250 L PH). In one embodiment described herein, the precipitation inhibitor comprises hydroxypropyl- methylcellulose (e.g., Benecel™ 250 L PH). Alkaline Neutralizing Agents In some embodiments, one or more alkaline neutralizing agents are added to the gel mass composition to solubilize the precipitation inhibitor and / or adjust the pH of the solution. Soluble or volatile alkali neutralizing agents, such as ammonia (NH4OH), sodium hydroxide, potassium hydroxide, ethylene diamine, hydroxylamine, triethylamine, or hydroalcoholic solutions of the same are useful. The alkali neutralizing agent is added such that the final pH of the gel mass is between pH 5–8. In one embodiment, the alkali is adjusted such that the pH does not exceed pH 7. The amount of alkaline neutralizing agent is typically 0.1 to 2% by mass of the gel mass. In one embodiment, the amount of alkaline neutralizing agent is quantum sufficit (q.s.) to adjust the pH to 5–8 and / or solubilize the precipitation inhibitor. This solution is subsequently mixed with one or more plasticizers and blended with gelatin to yield a gel mass. Antifoaming Agents In some embodiments, one or more antifoaming agents are incorporated into the gel mass composition to reduce foam generated when precipitation inhibitor is dissolved (during dissolution) in the gel mass. Surface-active properties of these agents help prevent foam formation during this process. Examples of antifoaming agents include dimethicone, silicone oil, simethicone, polydimethylsiloxane, polyethylene glycol, propylene glycol alginate, sorbitan stearate, stearyl alcohol, cetyl alcohol, glyceryl monostearate, magnesium stearate, calcium stearate, stearic acid, triethyl citrate, octadecanol, hydrogenated castor oil, beeswax, carnauba wax, and talc. The concentration of antifoaming agents may range from 0.1% to 1%. For example, one or more antifoaming agents may comprise a mass percentage of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, or 0.7%. In certain embodiments, an antifoaming agent may not be necessary unless foam generation affects solubility. Plasticizers Plasticizers and / or co-solvents that are useful for creating soft capsules as described herein are maltitol (hydrogenated corn syrup; e.g., Lycasin®, Roquette), sorbitol, glycerol, partially dehydrated sorbitol, a blend of D-sorbitol, 1,4-sorbitan, mannitol, and water; e.g., Sorbitol Special®(SPI Pharma); Anidrisorb®or Polysorb®, (Roquette), corn syrup, xylitol, mannitol, propylene glycol, low molecular weight polyethylene glycols, poly-alcohols with 3 to 6 carbon atoms, or a combination thereof. Plasticizers and / or co-solvents typically comprise a mass percentage of about 5–30% of the total wet mass of a shell, including each integer and fraction within the specified range. For example, one or more plasticizers or co-solvents may comprise a mass percentage of about 5%, 8%, 10%, 12%, 15%, 18%, 20%, 22%, 25%, 28%, or 30%, or about 5– 8%, 5–10%, 5–12%, 5–15%, 5–18%, 5–20%, 5–22%, 5–25%, 5–28%, 8–10%, 8–12%, 8–15%, 8–18%, 8–20%, 8–22%, 8–25%, 8–28%, 8–30%, 10–12%, 10–15%, 10–18%, 10–20%, 10–22%, 10–25%, 10–28%, 10–30%, 12–15%, 12–18%, 12–20%, 12–22%, 12–25%, 12–28%, 12–30%, 15–18%, 15–20%, 15–22%, 15–25%, 15–28%, 15–30%, 18–20%, 18–22%, 18–25%, 18–28%, 18–30%, 20–22%, 20–25%, 20–28%, 20–30%, 22–25%, 22–28%, 22–30%, 25–28%, 25–30%, or 28–30% of the total wet mass of a shell, including each integer and fraction within these specified values and ranges. In some embodiments, one or more plasticizers or co-solvents may comprise a mass percentage of about 10–20% of the total wet mass of a shell, including each integer and fraction within this specified range. In one non-limiting embodiment, one or more plasticizers or co-solvents may comprise a mass percentage of about 15–20%, or about 15–18%, of the total wet mass of a shell, including each integer and fraction within these specified ranges. The weight ratio between the film-forming polymer, plasticizer and / or co-solvent, and solvent is adjusted so that the gel mass is flowable and not too viscous and can be made into soft capsules using rotary die encapsulation methods. Disintegrating agents that are useful for creating soft capsules as described herein include, but are not limited to, sodium starch glycolate (“SSG”), croscarmellose sodium, crospovidone, calcium silicate, magnesium aluminum silicate, cross-linked alginic acid, or combinations thereof. In one aspect, the disintegrating agent is sodium starch glycolate. Disintegrating agents typically comprise a mass percentage of about 1–40% of the total wet mass of a shell, including each integer and fraction within the specified range. Solvents In some embodiments, the solvent comprises about 10% to about 45% by mass of the softgel capsule composition, including all integers and fractions within the specified range. In one embodiment, the solvent is water (e.g., purified water and / or extra purified water). The quantity of water in the composition varies depending on the quantities of the other ingredients. For example, the quantity of additional ingredients such as opacifiers, colorants, flavorings, or other excipients can change the percentage of water present in the composition. In one embodiment, the weight percentage of water is as much as suffices to bring the total mass percentage to 100% (i.e., quantum sufficiat; q.s.). In another embodiment, the water comprises about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, or about 45% by mass of the softgel capsule composition. In another embodiment, water comprises about 35% to about 40% of the softgel capsule composition. In one embodiment, water comprises about 37% by mass of the composition. The solvent typically comprises a mass percentage of about 10–45% of the total wet mass of a shell, including each integer and fraction within this specified range. For example, the solvent may comprise a mass percentage of about 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 45%, or about 10–15%, 10–20%, 10–25%, 10–30%, 10–35%, 10–40%, 15–20%, 15–25%, 15– 30%, 15–35%, 15–40%, 15–45%, 20–25%, 20–30%, 20–35%, 20–40%, 20–45%, 25–30%, 25– 35%, 25–40%, 25–45%, 30–35%, 30–40%, 30–45%, 35–40%, 35–45%, or 40–45% of the total wet mass of a shell, including each integer and fraction within these specified values and ranges. In some embodiments, the solvent may comprise a mass percentage of about 25–40% of the total wet mass of a shell, including each integer and fraction within this specified range. In one non- limiting embodiment, the solvent may comprise a mass percentage of about 30–40%, or about 35–40%, of the total wet mass of a shell, including each integer and fraction within these specified ranges. Additives and Excipients Other suitable shell additives include opacifiers, colorants, humectants, preservatives, viscosity modifiers, flavorings, and buffering salts and acids. Opacifiers can be used to opacify the capsule shell when the encapsulated active agents are light sensitive. Suitable opacifiers include titanium dioxide, zinc oxide, iron oxide, calcium carbonate and combinations thereof. When included in softgel capsule compositions, as described herein, opacifiers typically comprise a mass percentage of about 0.01–1% of the total wet mass of a shell, including each fraction within this specified range. For example, one or more opacifiers may comprise a mass percentage of about 0.01%, 0.1%, 0.25%, 0.5%, 0.75%, 0.9%, or 1%, or about 0.01–0.1%, 0.01–0.25%, 0.01–0.5%, 0.01–0.75%, 0.01–0.9%, 0.1–0.25%, 0.1– 0.5%, 0.1–0.75%, 0.1–0.9%, 0.1–1%, 0.25–0.5%, 0.25–0.75%, 0.25–0.9%, 0.25–1%, 0.5–0.75%, 0.5–0.9%, 0.5–1%, 0.75–0.9%, 0.75–1%, or 0.9–1% of the total wet mass of a shell, including each fraction within these specified values and ranges. In some embodiments, one or more opacifiers may comprise a mass percentage of about 0.01–1% of the total wet mass of a shell, including each fraction within this specified range. Colorants can be used to for marketing and product identification / differentiation purposes. Suitable colorants include synthetic and natural dyes and combinations thereof. When included in softgel capsule compositions, as described herein, colorants typically comprise a mass percentage of about 0.01–10% of the total wet mass of a shell, including each integer and fraction within this specified range. For example, one or more colorants may comprise a mass percentage of about 0.01%, 0.1%, 0.25%, 0.5%, 1%, 2%, 2.5%, 5%, 7.5%, or 10%, or about 0.01–0.1%, 0.01–0.25%, 0.01–0.5%, 0.01–1%, 0.01–2%, 0.01–2.5%, 0.01–5%, 0.01–7.5%, 0.1–0.25%, 0.1– 0.5%, 0.1–1%, 0.1–2%, 0.1–2.5%, 0.1–5%, 0.1–7.5%, 0.1–10%, 0.25–0.5%, 0.25–1%, 0.25–2%, 0.25–2.5%, 0.25–5%, 0.25–7.5%, 0.25–10%, 0.5–1%, 0.5–2%, 0.5–2.5%, 0.5–5%, 0.5–7.5%, 0.5–10%, 1–2%, 1–2.5%, 1–5%, 1–7.5%, 1–10%, 2–2.5%, 2–5%, 2–7.5%, 2–10%, 2.5–5%, 2.5– 7.5%, 2.5–10%, 5–7.5%, 5–10%, or 7.5–10% of the total wet mass of a shell, including each integer and fraction within these specified values and ranges. In some embodiments, one or more colorants may comprise a mass percentage of about 0.01–10% of the total wet mass of a shell, including each integer and fraction within this specified range. Humectants can be used to suppress the water activity of the softgel. Suitable humectants include glycerin and sorbitol, which are often components of the plasticizer composition. Due to the low water activity of dried, properly stored softgel capsules, the greatest risk from microorganisms comes from molds and yeasts. For this reason, preservatives can be incorporated into the capsule shell. Suitable preservatives include alkyl esters of p-hydroxy benzoic acid such as methyl, ethyl, propyl, butyl and heptyl (collectively known as “parabens”), or combinations thereof. Flavorings or “flavorants” can be used to mask unpleasant odors and tastes of fill formulations. Suitable flavorings include synthetic and natural flavorings. The use of flavorings can be problematic due to the presence of aldehydes which can cross-link gelatin. As a result, buffering salts and acids can be used in conjunction with flavorings that contain aldehydes in order to inhibit cross-linking of the gelatin. When included in softgel capsule compositions, as described herein, flavorings typically comprise a mass percentage of about 0.01–1% of the total wet mass of a shell, including each fraction within this specified range. For example, one or more flavorings may comprise a mass percentage of about 0.01%, 0.1%, 0.25%, 0.5%, 0.75%, 0.9%, or 1%, or about 0.01–0.1%, 0.01–0.25%, 0.01–0.5%, 0.01–0.75%, 0.01–0.9%, 0.1–0.25%, 0.1– 0.5%, 0.1–0.75%, 0.1–0.9%, 0.1–1%, 0.25–0.5%, 0.25–0.75%, 0.25–0.9%, 0.25–1%, 0.5–0.75%, 0.5–0.9%, 0.5–1%, 0.75–0.9%, 0.75–1%, or 0.9–1% of the total wet mass of a shell, including each fraction within these specified values and ranges. In some embodiments, one or more flavorings may comprise a mass percentage of about 0.01–1% of the total wet mass of a shell, including each fraction within this specified range. Examples of suitable viscosity modifiers include guar gum, locust bean gum, xanthan gum, agar, and gellan gum. Fillers or bulking agents can be added to the shell composition if needed. Useful fillers or bulking agents are hydroxypropyl starch phosphate, acacia, alginic acid, microcrystalline cellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, methylcellulose, ethylcellulose, pregelatinized starch, potato starch, tapioca starch, rice starch, corn starch, wheat starch, pea starch, modified starches, pregelatinized starch, microcrystalline cellulose, hydroxypropyl methylcellulose, lactose, dextrates, dextrin, dextrose, maltodextrin, glucose, sucrose, powdered sugar, sucrose syrup, mannitol, gums like xanthan gum, tragacantha, guar gum, acacia gum, arabic gum, ferula gummosa boiss, gum olibanum, beilschmiedia seed gum, aegle marmelos gum, okra gum, cassia roxburghii seeds gum, kaolin, talc, bentonite, calcium phosphates, calcium carbonate, magnesium carbonate, magnesium oxide, calcium sulphate, hydrogenated sodium chloride, potassium chloride, combinations or mixtures thereof, and others known in the art. Other useful fillers are N-Lok®, (starch sodium octenyl succinate), Hi-Cap™, and Ultra Sperse®M. In some embodiments, the soft capsule shell composition comprises a top coating or a moisture barrier that is applied to the capsule shell. In one embodiment, the moisture barrier comprises one or more polyvinyl alcohols (PV) and appropriate pharmaceutically acceptable excipients. In one embodiment, the moisture barrier comprises polyvinyl alcohol, sodium lauryl sulfate, glyceryl mono-caprylate-caprate, and talc. In one aspect, the moisture barrier aids in preserving the cosmetic appearance of the dosage forms by preventing dimpling, sticking, or other processing or storage induced blemishes. The top coating may also comprise a sealant. In one aspect, the sealant can be a methacrylic acid copolymer, hydroxypropylmethylcellulose, or a proprietary sealant such as Kollicoat®Protect (BASF). Coatings, top coatings, or subcoatings are applied to the soft capsules using various methods known in the art. The coatings are typically prepared as suspensions and sprayed on capsules in perforated coating pans through one or more spray nozzles at a specific temperature. Coating solutions or dispersion may be applied at spray rates between 100 and 400 g / min. The spray rate may be proportionately higher for coatings with higher solid content and lower for more dilute dispersions. In one embodiment, capsules are coated using a pan coater. After the coating suspension is applied, the coated capsules are dried in the pan coater for a period of time at a specific temperature. In some embodiments, a softgel capsule as described herein may enrobe or encapsulate a pressed tablet comprising one or more active pharmaceutical ingredients for easier swallowing of the pressed tablet by a subject. As used herein, “enrobe” generally refers to coating a pressed tablet with a softgel capsule formulation to form an “enrobed tablet.” As used herein, “encapsulate” generally refers to coating a pressed tablet with a softgel capsule formulation to form an “encapsulated tablet,” where additional components or excipients may be present in the encapsulated tablet. In some embodiments, a softgel capsule as described herein may have one or more active pharmaceutical ingredients incorporated into the softgel capsule formulation in addition to or instead of in the matrix fill. In some embodiments, a precipitation inhibitor softgel capsule as described herein may be utilized in chewable soft capsules containing solid, semisolid, gelatinous, or liquid fills, e.g., Chewels® or LiquiSoft® (Patheon Softgels Inc). See e.g., U.S. Pat. Nos.8,097,279; 8,241,665; 8,765,174; 8,414,916; 9,072,677; 9,668,976; 9,861,586; 10,342,763; 9,867,779; and 10,555,901 each of which is incorporated by reference herein for such teachings. In some embodiments, precipitation inhibitor softgel capsules may also be pre-stressed to enhance the release rate. Exemplary examples of pre-stressing include laser drilling, mechanical drilling, scoring, or other known means to pre-stress the gel capsule. Fill Compositions Fill compositions for the softgel capsules described herein can be aqueous or oil-based fills. Aqueous fills typically contain one or more polyethylene glycols, solubilizers, and other pharmaceutical excipients in addition to the API. Oil-based fills contain oils, waxes, surfactants, and other pharmaceutical excipients in addition to the API. Exemplary fill compositions are shown in Table 2. In one embodiment, BCS Class II APIs are particularly suited for use with the precipitation inhibitor softgel capsules because these APIs often precipitate in subject’s intestines. Table 2: Exemplary Precipitation Inhibitor Capsule Fill Components Component Examples Mass Range (mg) Active Pharmaceutical IngredientsAny, but particularlyBCS Class II APIs 0.1–2000Nutraceuticals Agent Any 0.1–2000 Neutralizing Agents Any compatible 0.1–2000 Solvents Any compatible 0.1–2000 Co-solvents Any compatible 0.1–2000 Surfactants Any compatible 0.1–2000 Co-surfactants Any 0.1–2000 Theoretical Total Fill Weight 0.1–2000 mg In one embodiment, the fill contains one or more hydrophilic vehicles which may be anhydrous and compatible with soft gelatin capsules. Non-limiting exemplary vehicles comprise Capmul®MCM, Captex®355, Cremophor®RH 40, Croscarmellose, Crospovidone, Crospovidone CL, Crospovidone CL-F, Crospovidone CL-M, Imwitor®742, Kollidon®CL, Kollidon®CL-F, Kollidon®CL-M, Labrafac™ Lipophile WL 1349, Labrafil®M2125CS, Labrasol®, Lutrol®F 68, Maisine™ 35-1, mannitol, Miglyol®812, Pearlitol®Flash, Peceol®, Plurol®Oleique CC 497, Povidone K 17, Povidone K 30, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyethylene glycol 3350, propylene glycol, glycerol, Lycasin 80 / 55, sorbitol special, xylitol, maltitol or mixtures thereof. In one embodiment, the hydrophilic vehicle comprises one or more hydro-alcohols including polyethylene glycols of a molecular weight ranging from about 200 to about 8000, or a mixture or combination thereof. In another embodiment, the hydrophilic vehicle may comprise a hygroscopic polymer. In one embodiment, the hygroscopic polymers include polyvinylpyrrolidone, crospovidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, ethyl cellulose, methylcellulose, and polyethylene oxide. Suitable hygroscopic polymers include polyvinyl alcohol, a copolymer of polyvinylpyrrolidone and polyvinyl acetate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, gelatin, polyethylene oxide, such as POLYOX™ 100,000–600,000 MW, acacia, dextrin, cyclodextrins, starch, poly hydroxyethylmethacrylate, a water-soluble non-ionic polymethacrylate or copolymer thereof, a modified cellulose, a modified polysaccharide, a non-ionic gum, or a non-ionic polysaccharide. In another embodiment, the fill may comprise one or more lipids or lipophilic vehicles. In one aspect, the lipid or lipophilic vehicle may be a liquid or a solid or a semisolid lipid or lipophilic vehicle. Suitable non-limiting liquid lipid or lipophilic vehicles comprise olive oil, soybean oil, sunflower oil, canola oil, palmitoleic acid, oleic acid, myristoleic acid, linoleic acid, arachidonic acid, paraffin oil, mineral oil, or a mixture or combination thereof. The lipid or lipophilic vehicle can be a semi-solid lipophilic vehicle such as a polyethylene glycol glyceride ester, e.g., Gelucire®33 / 01, Gelucire®37 / 02, Gelucire®39 / 01, Gelucire®43 / 01, Gelucire®44 / 14, Gelucire®50 / 02, Gelucire®50 / 13, Gelucire®53 / 10, or Gelucire®62 / 02; a paraffin wax, carnauba wax, or bee’s wax. In another embodiment, the fill may comprise release regulators such as fatty acid salts, fatty acid esters, or fatty acid polyoxyethylene derivatives. The release regulator can also be a surfactant having a hydrophilic / lipophilic balance (HLB) value between about 2 and about 40. The HLB characteristic of surfactants can be determined in accordance with “Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences,” Fourth Edition, pp. 371-373, A. Martin, Ed., Lippincott Williams & Wilkins, Philadelphia (1993), which is incorporated by reference herein for such teachings. In another embodiment, the fill may comprise emulsifying or solubilizing agents such as acacia, cholesterol, diethanolamine, glyceryl monostearate, lanolin alcohols, lecithin, mono- and di-glycerides, monoethanolamines, oleic acids, oleyl alcohols, poloxamer, polyoxyethylene 50 stearate, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, propylene glycol diacetate, propylene glycol monostearate, sodium lauryl sulfate, sodium stearate, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, stearic acid, simethicone, trolamine, emulsifying wax, or combinations thereof. Other suitable solvents include surfactants and copolymers of polyethylene glycols of a molecular weight ranging from about 200 to about 8000. Optionally, glycerin, polyvinyl pyrrolidone (PVP) or propylene glycol (PG) can be added to enhance the solubility of the drug agent. In another embodiment described herein, the matrix fill comprises one or more flavorings. In one embodiment, the one or more flavorings comprise citric acid, lactic acid, sodium citrate, anethole, benzaldehyde, ethyl vanillin, Eucalyptol, glycine, menthol, methyl salicylate, monosodium glutamate, orange flower oil, peppermint, peppermint oil, peppermint spirit, rose oil, stronger rose water, thymol, tolu balsam tincture, vanilla, vanilla tincture, vanillin, or combinations thereof. In one aspect, the flavorings comprise one or more of citric acid, acetic acid, lactic acid, malic acid, tartaric acid, or combinations thereof. In another aspect, the flavorings comprise citric acid, lactic acid, or combinations thereof. In another embodiment, the matrix fill comprises at least one or more sweeteners. In one embodiment, the one or more sweeteners comprise mannitol, thaumatin, glycyrrhizic acid salt, maltitol, sucralose, acesulfame salts, steviol glycosides (e.g., Stevia®, Truvía®), saccharin, calcium saccharin, sodium saccharin, aspartame, acesulfame potassium, agave nectar, high- fructose corn syrup, honey, dextrates, dextrose, excipient dextrose and simple sugars such as glucose, fructose, sucrose, sucralose, lactose, or combinations thereof. In one aspect, the sweeteners comprise one or more of mannitol, maltitol (e.g., Lycasin®), xylitol, sucralose, thaumatin (e.g., Talin®), glycyrrhizic acid salts (MagnaSweet®), or combinations thereof. In another embodiment, the matrix fill comprises at least one solvent. In one aspect, the solvent is water. The matrix fill can optionally include one or more pharmaceutically acceptable excipients. Examples of pharmaceutically acceptable excipients include buffers, such as phosphate buffers, citrate buffer, and buffers with other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers, such as polyvinyl pyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates, including glucose, mannose, or dextrins; chelating agents, such as EDTA; sugar alcohols, such as mannitol or sorbitol; salt-forming counterions, such as sodium; and / or nonionic surfactants, such as TWEEN®(ICI, Inc.; Bridgewater, New Jersey), and PLURONICS™ (BASF; Florham Park, NJ). Diluents commonly used in the art can also be encapsulated within the shell, including water or other solvents, solubilizing agents, and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, 1,3-butylene glycol, dimethylformamide, oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil, sesame oil, glycerol, tetrahydrofurfuryl alcohol, and fatty acid esters of sorbitan, and mixtures of these substances. Additional pharmaceutical excipients useful for matrix fills include, for example, the following: Acidifying agents (acetic acid, glacial acetic acid, citric acid, fumaric acid, hydrochloric acid, diluted hydrochloric acid, malic acid, nitric acid, phosphoric acid, diluted phosphoric acid, sulfuric acid, tartaric acid); Alkalizing agents (ammonia solution, ammonium carbonate, diethanolamine, diisopropanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine); Antifoaming agents (dimethicone, simethicone); Antimicrobial preservatives (benzalkonium chloride, benzalkonium chloride solution, benzethonium chloride, benzoic acid, benzyl alcohol, butylparaben, cetylpyridinium chloride, chlorobutanol, chlorocresol, cresol, dehydroacetic acid, ethylparaben, methylparaben, methylparaben sodium, phenol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric nitrate, potassium benzoate, potassium sorbate, propylparaben, propylparaben sodium, sodium benzoate, sodium dehydroacetate, sodium propionate, sorbic acid, thimerosal, thymol); Antioxidants (ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium thiosulfate, sulfur dioxide, tocopherol, tocopherols excipient); Buffering agents (acetic acid, ammonium carbonate, ammonium phosphate, boric acid, citric acid, lactic acid, phosphoric acid, potassium citrate, potassium metaphosphate, potassium phosphate monobasic, sodium acetate, sodium citrate, sodium lactate solution, dibasic sodium phosphate, monobasic sodium phosphate); Chelating agents (edetate disodium, ethylenediaminetetraacetic acid and salts, edetic acid); Coating agents (sodium carboxymethylcellulose, cellulose acetate, cellulose acetate phthalate, ethylcellulose, gelatin, pharmaceutical glaze, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, methacrylic acid copolymer, methylcellulose, polyvinyl acetate phthalate, shellac, sucrose, titanium dioxide, carnauba wax, microcrystalline wax, zein); Colorants (caramel, red, yellow, black or blends, ferric oxide); Complexing agents (ethylenediaminetetraacetic acid and salts (EDTA), edetic acid, gentisic acid ethanolamide, oxyquinoline sulfate); Desiccants (calcium chloride, calcium sulfate, silicon dioxide); Emulsifying and / or solubilizing agents (acacia, cholesterol, diethanolamine (adjunct), glyceryl monostearate, lanolin alcohols, mono- and di-glycerides, monoethanolamine (adjunct), lecithin, oleic acid (adjunct), oleyl alcohol (stabilizer), poloxamer, polyoxyethylene 50 stearate, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, diacetate, monostearate, sodium lauryl sulfate, sodium stearate, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, stearic acid, trolamine, emulsifying wax); Filtering aids (powdered cellulose, purified siliceous earth); Flavors and perfumes (anethole, benzaldehyde, ethyl vanillin, menthol, methyl salicylate, monosodium glutamate, orange flower oil, peppermint, peppermint oil, peppermint spirit, rose oil, stronger rose water, thymol, tolu balsam tincture, vanilla, vanilla tincture, vanillin); Humectants (glycerin, hexylene glycol, sorbitol); Plasticizers (e.g., castor oil, diacetylated monoglycerides, diethyl phthalate, glycerin, mono- and di-acetylated monoglycerides, propylene glycol, triacetin, triethyl citrate); Polymers (e.g., cellulose acetate, alkyl celluloses, hydroxyalkyl, acrylic polymers and copolymers); Solvents (acetone, alcohol, diluted alcohol, amylene hydrate, benzyl benzoate, butyl alcohol, carbon tetrachloride, chloroform, corn oil, cottonseed oil, ethyl acetate, glycerin, hexylene glycol, isopropyl alcohol, methyl alcohol, methylene chloride, methyl isobutyl ketone, mineral oil, peanut oil, propylene carbonate, sesame oil, water for injection, sterile water for injection, sterile water for irrigation, purified water); Sorbents (powdered cellulose, charcoal, purified siliceous earth); Carbon dioxide sorbents (barium hydroxide lime, soda lime); Stiffening agents (hydrogenated castor oil, cetostearyl alcohol, cetyl alcohol, cetyl esters wax, hard fat, paraffin, polyethylene excipient, stearyl alcohol, emulsifying wax, white wax, yellow wax); Suspending and / or viscosity-increasing agents (acacia, agar, alginic acid, aluminum monostearate, bentonite, purified bentonite, magma bentonite, carbomer, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carboxymethylcellulose sodium, carrageenan, microcrystalline and carboxymethylcellulose sodium cellulose, dextrin, gelatin, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium aluminum silicate, methylcellulose, pectin, polyethylene oxide, polyvinyl alcohol, povidone, alginate, silicon dioxide, colloidal silicon dioxide, sodium alginate, tragacanth, xanthan gum); Sweetening agents (aspartame, dextrates, dextrose, excipient dextrose, fructose, mannitol, saccharin, calcium saccharin, sodium saccharin, sorbitol, solution sorbitol, sucrose, compressible sugar, confectioner’s sugar, syrup); Tablet binders (acacia, alginic acid, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethylcellulose, gelatin, liquid glucose, guar gum, hydroxypropyl methylcellulose, methylcellulose, polyethylene oxide, povidone, pregelatinized starch, syrup); Tablet and / or capsule diluents (calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, powdered cellulose, dextrates, dextrin, dextrose excipient, fructose, kaolin, lactose, mannitol, sorbitol, starch, pregelatinized starch, sucrose, compressible sugar, confectioner’s sugar); Tablet disintegrants (alginic acid, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, starch, pregelatinized starch); Tablet and / or capsule lubricants (calcium stearate, glyceryl behenate, magnesium stearate, light mineral oil, sodium stearyl fumarate, stearic acid, purified stearic acid, talc, hydrogenated vegetable oil, zinc stearate); Tonicity agent (dextrose, glycerin, mannitol, potassium chloride, sodium chloride); Vehicle: flavored and / or sweetened (aromatic elixir, compound benzaldehyde elixir, iso-alcoholic elixir, peppermint water, sorbitol solution, syrup, tolu balsam syrup); Vehicle: oleaginous (almond oil, corn oil, cottonseed oil, ethyl oleate, isopropyl myristate, isopropyl palmitate, mineral oil, light mineral oil, myristyl alcohol, octyldodecanol, olive oil, peanut oil, persic oil, sesame oil, soybean oil, squalane); Vehicle: solid carrier (sugar spheres); Vehicle: sterile (Bacteriostatic water for injection, bacteriostatic sodium chloride injection); Viscosity-increasing (see suspending agent); Water repelling agent (cyclomethicone, dimethicone, simethicone); and / or solubilizing agent (benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, docusate sodium, nonoxynol 9, nonoxynol 10, octoxynol 9, poloxamer, polyoxyl 35 castor oil, polyoxyl 40, hydrogenated castor oil, polyoxyl 50 stearate, polyoxyl 10 oleyl ether, polyoxyl 20, cetostearyl ether, polyoxyl 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, sodium lauryl sulfate, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, tyloxapol). This list is not meant to be exclusive, but instead merely representative of the classes of excipients and the particular excipients that may be used in the softgel dosage forms as described herein. In one embodiment, the matrix fill can include a release regulator such as a fatty acid salt, fatty acid ester, or fatty acid polyoxyethylene derivative. The release regulator can also be a surfactant having a hydrophilic / lipophilic balance (HLB) value between about 2 and about 40. The HLB characteristic of surfactants can be determined in accordance with Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences, 4thed., 371-373, A. Martin, Ed., Lippincott Williams & Wilkins, Philadelphia (1993), which is incorporated by reference herein for such teachings. In one embodiment, the matrix fill may include one or more hydrophilic carriers. Examples of hydrophilic carriers are all natural, synthetic, or semi-synthetic products, which can be defined as aqueous carriers not mixable or only partially mixable with oil. All components can be used alone or if possible, in mixtures with different percentages. Among aqueous components which can be used as a dispersing phase or also as a dispersed phase. Examples of aqueous solutions of hydrophilic polymers, which are hydrosoluble or hydrodispersable of various nature, such as polyethylenglycol, polyvinyl pyrrolidone, polyacrylic acids and derivatives, such as Carbopol®971, polymethacrylic acids polyoxyethylenepolyoxypropylene copolymers (for example Poloxamer®, Lutrol™), hydrophilic polysaccharides of various nature, for example dextran, xanthan, scleroglucan, arabic gum, guar gum, chitosan, cellulose, or starch derivatives. In one embodiment, the matrix fill can include a neutralizing agent. In one aspect, the neutralizing agent comprises an organic acid, ester, or salt. In another aspect, the neutralizing agent comprises at least one of lactate, fumarate, caprylate, caprate, oleate, maleate, succinate, tartrate, citrate, glutamate, gluconate, esters or salts thereof, or combinations thereof. In one embodiment, the matrix fill can include a hydrophilic internal phase and a lipid or lipophilic external phase. The internal phase of the matrix fill can include a plasticizer, such as propylene glycol, or a solubility enhancing agent, such as polyethylene glycol of molecular mass ranging from about 200 g / mol to about 8000 g / mol. In another embodiment, the internal phase can include hydroalcoholic solutions of cellulose derivatives, hydrophilic polymers, polyacrylates, polyacrylic acids and derivatives (e.g., Carbopol™) polyvinyl polymers, chitosan, or combinations thereof. In another embodiment, the internal phase of the matrix fill can include polymers, such as methylcellulose, hydroxypropylmethylcellulose, polymethylmethacrylate, or polyvinylpyrrolidone (PVP). The internal phase of the matrix fill can also be structured. A “structured” internal phase of the matrix fill, as used herein, means a solid, semisolid, or a gel whose shape is relatively stable and does not usually aggregate to form a large globule. A structured internal phase of the matrix fill therefore provides controlled drug release and stabilizes the physical state of the matrix. Without being bound by any theory, it is believed that the structured nature of the matrix fill impedes solvation and / or diffusion of the active pharmaceutical ingredient out of the matrix fill. In another embodiment, the external phase of the matrix fill can include a vegetable oil, hydrogenated vegetable oil (including shortening), fatty acids, fatty acid esters, wax, bee’s wax, soybean oil, or a combination thereof. In another embodiment, an active pharmaceutical ingredient can be dispersed in the internal phase of the matrix fill as a suspension form. In one embodiment, the matrix fill is a liquid (e.g., a solution, suspension, or dispersion) or a semisolid (e.g., a paste or gel). In one aspect, the active pharmaceutical ingredient can be innately a liquid or semisolid. In another aspect, the active ingredient can be prepared as a liquid or semisolid by, for example, by dissolving or otherwise mixing an active ingredient and optionally one or more pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, glycerol, glycols (e.g., propylene glycol), ethanol, fatty acids, glycerides, oils, sterols, phospholipids, and the like, to thereby form a solution. In one embodiment described herein, the matrix fill comprises a lipid or lipophilic vehicle that provides a suspension of an active pharmaceutical ingredient having defined sizes. In one aspect, a soft capsule comprising a suspension of an active pharmaceutical ingredient provides rapid release delivery of the active pharmaceutical ingredient. In one embodiment described herein, the pharmaceutical composition provides matrix fills for an active pharmaceutical ingredient, or derivatives thereof, based on lipids or lipophilic materials. The described matrices have a hydrophobic (lipophilic) surface in contact with a hydrophilic soft capsule shell to minimize any potential shell-fill interactions, such as when the soft capsules are filled with hydrophilic materials. APIs Examples of active pharmaceutical ingredients that can be included comprise agents classified as, for example, an adrenocortical steroid, adrenocortical suppressant, aldosterone antagonist, amino acid, anabolic steroid, androgen, antagonist, anthelmintic, anti-acne agent, anti-adrenergic, anti-allergic, anti-amebic, anti-androgen, anti-anemic, anti-anginal, anti-arthritic, anti-asthmatic, anti-atherosclerotic, antibacterial, anticholelithic, anticholelithogenic, anticholinergic, anticoagulant, anticoccidal, antidiabetic, antidiarrheal, antidiuretic, antidote, anti- estrogen, antifibrinolytic, antifungal, antiglaucoma agent, antihemophilic, antihemorrhagic, antihistamine, antihyperlipidemic, antihyperlipoproteinemic, antihypertensive, antihypotensive, anti-infective, anti-infective, anti-inflammatory, antikeratinizing agent, antimalarial, antimicrobial, antimitotic, antimycotic, antineoplastic, antineutropenic, antiparasitic, antiperistaltic, antipneumocystic, antiproliferative, antiprostatic hypertrophy, antiprotozoal, antipruritic, antipsoriatic, antirheumatic, antischistosomal, antiseborrheic, antisecretory, antispasmodic, antithrombotic, antitussive, anti-ulcerative, anti-urolithic, antiviral, appetite suppressant, benign prostatic hyperplasia therapy agent, bone resorption inhibitor, bronchodilator, carbonic anhydrase inhibitor, cardiac depressant, cardioprotectant, cardiotonic, cardiovascular agent, choleretic, cholinergic, cholinergic agonist, cholinesterase deactivator, coccidiostat, contrasting agent, diagnostic aid, diuretic, ectoparasiticide, enzyme inhibitor, estrogen, fibrinolytic, free oxygen radical scavenger, glucocorticoid, gonad-stimulating principle, hair growth stimulant, hemostatic, hormone, hypocholesterolemic, hypoglycemic, hypolipidemic, hypotensive, imaging agent, immunizing agent, immunomodulator, immunoregulator, immunostimulant, immunosuppressant, impotence therapy adjunct, inhibitor, keratolytic, LHRH agonist, liver disorder treatment, luteolysin, mucolytic, mydriatic, nasal decongestant, neuromuscular blocking agent, non- hormonal sterol derivative, nonsteroidal anti-inflammatory drugs, oxytocic, plasminogen activator, platelet activating factor antagonist, platelet aggregation inhibitor, potentiator, progestin, prostaglandin, prostate growth inhibitor, prothyrotropin, radioactive agent, regulator, relaxant, repartitioning agent, scabicide, sclerosing agent, selective adenosine A1 antagonist, steroid, suppressant, symptomatic multiple sclerosis, synergist, thyroid hormone, thyroid inhibitor, thyromimetic, amyotrophic lateral sclerosis agents, Paget’s disease agents, unstable angina agents, uricosuric, vasoconstrictor, vasodilator, vulnerary, wound healing agent, and xanthine oxidase inhibitor. Further examples of suitable pharmaceutical ingredients include those as listed in the Merck Index (13thEdition, Wiley, 2001), The United States Pharmacopeia–National Formulary (USP–NF), and the FDA’s Orange book, which are each incorporated by reference herein for their teachings of pharmaceutically active ingredients. The formulation can contain any therapeutic, diagnostic, prophylactic or nutraceutical agent. Exemplary agents include, but are not limited to, analeptic agents; analgesic agents; anesthetic agents; antiasthmatic agents; antiarthritic agents; anticancer agents; anticholinergic agents; anticonvulsant agents; antidepressant agents; antidiabetic agents; antidiarrheal agents; antiemetic agents; antihelminthic agents; antihistamines; antihyperlipidemic agents; antihypertensive agents; anti-infective agents; anti-inflammatory agents; antimigraine agents; antineoplastic agents; antiparkinson drugs; antipruritic agents; antipsychotic agents; antipyretic agents; antispasmodic agents; antitubercular agents; antiulcer agents; antiviral agents; anxiolytic agents; appetite suppressants (anorexic agents); attention deficit disorder and attention deficit hyperactivity disorder drugs; cardiovascular agents including calcium channel blockers, antianginal agents, central nervous system (“CNS”) agents, beta-blockers and antiarrhythmic agents; central nervous system stimulants; diuretics; genetic materials; hormonolytics; hypnotics; hypoglycemic agents; immunosuppressive agents; muscle relaxants; narcotic antagonists; nicotine; nutritional agents; parasympatholytics; peptide drugs; psychostimulants; sedatives; sialagogues, steroids; smoking cessation agents; sympathomimetics; tranquilizers; vasodilators; beta-agonist; and tocolytic agents. A first class of drugs is selected based on inclusion in the molecule of a weakly acidic, basic, or amphoteric group that can form a salt. Any drug that bears an acidic or a basic functional group, for example, an amine, imine, imidazoyl, guanidine, piperidinyl, pyridinyl, quaternary ammonium, or other basic group, or a carboxylic, phosphoric, phenolic, sulfuric, sulfonic, or other acidic group, can react with the de-ionizing agent. Some specific drugs that bear acidic or basic functional groups and thus may be converted to the corresponding salt for use in the described formulations include, but are not limited to, acetaminophen, acetylsalicylic acid, alendronic acid, alosetron, amantadine, amlodipine, anagrelide, argatroban, atomoxetine, atorvastatin, azithromycin dehydrate, balsalazide, bromocriptin, bupropion, candesartan, carboplatin, ceftriaxone, clavulanic acid, clindamycin, cimetadine, dehydrocholic (acid), dexmethylphenidate, diclofenac, dicyclomine, diflunisal, diltiazem, donepezil, doxorubicin, doxepin, epirubicin, etodolic acid, ethacrynic acid, fenoprofen, fluoxetine, flurbiprofen, furosemide, gemfibrozil, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoprofen, levothyroxine, maprotiline, meclizine, methadone, methylphenidate, minocycline, mitoxantrone, moxifloxacin, mycophenolic acid, naproxen, niflumic acid, ofloxacin, ondansetron, pantoprazole, paroxetine, pergolide, pramipexole, phenytoin, pravastatin, probenecid, rabeprazole, risedronic acid, retinoic acid, ropinirole, selegiline, sulindac, tamsulosin, telmisartan, terbinafine, theophyline, tiludronic acid, tinzaparin, ticarcillin, tomentin, valproic acid, salicylic acid, sevelamer, ziprasidone, zoledronic acid, acetophenazine, albuterol, almotriptan, amitriptyline, amphetamine, atracurium, beclomethasone, benztropine, biperiden, bosentan, bromodiphenhydramine, brompheniramine carbinoxamine, caffeine, capecitabine, cabergoline, cetirizine, chlocylizine, chlorpheniramine, chlorphenoxamine, chlorpromazine, citalopram, clavulanate potassium, ciprofloxacin, clemastine, clomiphene, clonidine, clopidogrel, codeine, cyclizine, cyclobenzaprine, cyproheptadine, delavirdine, diethylpropion, divalproex, desipramine, dexmethylphenidate, dexbrompheniramine, dexchlopheniramine, dexchlor, dextroamphetamine, dexedrine, dextromethorphan, fiflunisal, diphemanil methylsulphate, diphenhydramine, dolasetron, doxylamine, enoxaparin, ergotamine, ertepenem, eprosartan, escitalopram, esomeprazole, fenoldopam, fentanyl, fexofenadine, flufenamic acid, fluvastatin, fluphenazine, fluticasone, fosinopril, frovatriptan, gabapentin, galatamine, gatifloxacin, gemcitabine, haloperidol, hyalurondate, hydrocodone, hydroxychloroquine, hyoscyamine, imatinib, imipenem, ipatropin, lisinopril, leuprolide, levopropoxyphene, losartan, meclofenamic acid, mefanamic acid, mesalamine, mepenzolate, meperidine, mephentermine, mesalimine, mesoridazine, metaproteranol, metformin, methdialazine, methscopolamine, methysergide, metoprolol, metronidazole, mibefradil, montelukast, morphine, mometasone, naratriptan, nelfinavir, nortriptylene, noscapine, nylindrin, omeprazole, orphenadrine, oseltamivir, oxybutynin, papaverine, pentazocine, phendimetrazine, phentermine, pioglitazone, pilocarpine, prochloroperazine, pyrilamine, quetapine, ranitidine, rivastigmine, rosiglitazone, salmetrol, sertaline, sotalol, sumatriptan, tazobactam, tacrolimus, tamoxifen, ticlopidine, topiramate, tolterodine, triptorelin, triplennamine, triprolidine, tramadol, trovofloxacin, ursodiol, promazine, propoxyphene, propanolol, pseudoephedrine, pyrilamine, quinidine, oxybate sodium, sermorelin, tacrolimus, tegaseroid, teriparatide, tolterodine, triptorelin pamoate, scoplolamine, venlafaxine, zamivir, aminocaproic acid, aminosalicylic acid, hydromorphone, isosuprine, levorphanol, melhalan, nalidixic acid, and para-aminosalicylic acid. In one embodiment, the compositions described herein comprise one or more active pharmaceutical ingredients useful for treating, retarding the progression of, delaying the onset of, prophylaxis of, amelioration of, or reducing the symptoms of pain, inflammation, fever, or symptoms stemming from cough or cold. In one embodiment described herein, the active pharmaceutical ingredient comprises one or more of astemizole, azelastine, azatadine, brompheniramine, carbinoxamine, cetirizine, chlorpheniramine, clemastine, cyproheptadine, desloratadine, dexbrompheniramine, dexchlorpheniramine, diphenhydramine, fexofenadine, hydroxyzine, levocetirizine, loratadine, phenindamine, pheniramine, phenyltoloxamine, promethazine, pyrilamine, terfenadine, tripelennamine, triprolidine, acetyl dihydrocodeine, benproperine, benzonatate, benzylmorphine, bibenzonium bromide, butamirate, butorphanol, carbetapentane, chlophedianol, clobutinol, clofedanol, cloperastine, codeine, dextromethorphan, diacetylmorphine, dibunate, dihydrocodeine, dimemorfan, dimethoxanate, diphenhydramine, dropropizine, droxypropine, ethylmorphine, fedrilate, glaucine, hydrocodone, hydromorphone, isoaminile, laudanum, levodropropizine, levomethadone, levopropoxyphene, meprotixol, methadone, morclofone, nepinalone, nicocodine, nicodicodine, normethadone, noscapine, oxeladin, oxolamine, pentoxyverine, pholcodine, pipazetate, piperidione, prenoxdiazine, tipepidine, zipeprol, acetylcysteine, althea root, ambroxol, antimony pentasulfide, bromhexine, carbocisteine, cineole, combinations, combinations, creosote, dembrexine hydrochloride, domiodol, dornase alfa, eprazinone, erdosteine, guaiacolsulfonate, guaifenesin, hederae helicis folium, ipecacuanha, letosteine, levo verbenone, mannitol, mesna, neltenexine, potassium iodide, senega, sobrerol, stepronin, tiopronin, tyloxapol, or combinations thereof. In one aspect, the active pharmaceutical ingredient comprises one or more of dextromethorphan hydrobromide, menthol, or combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient is an anti- allergy agent. Exemplary anti-allergy agents include pseudoephedrine, cetirizine, loratadine, fexofenadine, diphenhydramine, levocetirizine, desloratadine, or combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient is an oral rinsing agent. Exemplary oral rinsing agents include phenol, ethanol, thymol, eucalyptol, ethanol, methyl salicylate, chlorhexidine gluconate, cetylpyridinium chloride, hexetidine, triclosan, hydrogen peroxide, domiphen bromide, or combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient comprises an oral rinsing agent comprising one or more of ethanol (about 20% to about 30%) menthol (0.042%), thymol (0.064%), methyl salicylate (0.06%), and eucalyptol (0.092%). In one embodiment described herein, the active pharmaceutical ingredient is an antidiarrheal or antacid comprising bismuth subsalicylate, loperamide hydrochloride, aluminum hydroxide, magnesium hydroxide, simethicone, aluminum carbonate, calcium carbonate, sodium bicarbonate, magnesium aluminum silicate, hydrotalcite, magaldrate, cimetidine, famotidine, nizatidine, ranitidine, lansoprazole, omeprazole, esomeprazole, rabeprazole, pantoprazole, dexlansoprazole, or combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient comprises one or more of bismuth subsalicylate (~17.6 mg), benzoic acid, D&C Red No. 22, D&C Red No. 28, flavoring, magnesium aluminum silicate, methylcellulose, sodium saccharin, salicylic acid, sodium salicylate, sorbic acid, and water. In another embodiment, the active pharmaceutical ingredient is an irritable bowel syndrome therapeutic. Exemplary non-limiting active pharmaceutical ingredients useful for the treatment of irritable bowel syndrome comprise antidiarrheals such as atropine, diphenoxylate (Lomotil®), dicyclomine (Bentyl®), loperamide (Imodium®), rifaximin (Xifaxan®), alosetron (Lotronex®); bile acid binding agents such as cholestyramine (Prevailite®); constipation therapeutics such as linaclotide (Linzess®) or lubiprostone (Amitiza) or combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient is a constipation therapeutic such as linaclotide (Linzess®) or lubiprostone (Amitiza®), methylcellulose, polycarbophil, psyllium, mineral oil, glycerol, docusate sodium, sodium bicarbonate, sodium phosphate, magnesium citrate, magnesium oxide, magnesium sulfate, bisacodyl, sennosides, senna, castor oil or combinations thereof. In another embodiment described herein, the active pharmaceutical ingredient comprises one or more corticosteroids for treating inflammatory diseases and conditions and inflammation of the gastrointestinal tract, including but not limited to esophageal inflammation. In one embodiment described herein, the active pharmaceutical ingredient comprises one or more corticosteroids including but not limited to alclometasone, amcinonide, beclometasone, betamethasone, budesonide, ciclesonide, clobetasol, clobetasone, clocortolone, cloprednol, cortivazol, deflazacort, deoxycorticosterone, desonide desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, fluclorolone, fludrocortisone, fludroxycortide, flumetasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin, fluocortolone, fluorometholone, fluperolone, fluticasone, fluticasone propionate, fluprednidene, formocortal, halcinonide, halometasone, hydrocortisone aceponate, hydrocortisone buteprate, hydrocortisone butyrate, loteprednol, medrysone, meprednisone, methylprednisolone, methylprednisolone aceponate, mometasone furoate, paramethasone, prednicarbate, prednisone, prednisolone, prednylidene, rimexolone, tixocortol, triamcinolone, ulobetasol, combinations thereof, or pharmaceutically acceptable salts, or esters thereof. In another embodiment described herein, the active pharmaceutical ingredient comprises one or more of 5-fluorouracil, 5-fluorodeoxyuridine, capecitabine, derivatives thereof, or combinations thereof for treating neoplasia, including but not limited to head and neck neoplasia. In another embodiment described herein, the active pharmaceutical ingredient comprises one or more of calcium supplements or calcimimetics including but not limited to cinacalcet, derivatives thereof, or combinations thereof for treating hyperthyroidism, hypercalcemia, hyperparathyroidism, parathyroid carcinoma, or a combination thereof. In some embodiments, the active pharmaceutical ingredient is a sleep aid. Examples of sleep aids include, but are not limited to doxylamine, diphenhydramine hydrochloride, melatonin, l-theanine, or combinations thereof. In some embodiments, the active pharmaceutical ingredient is an oral saliva substitute, such as, for example: monofluorophosphate, lactoferrin, lysozyme, lactoperoxidase, glucose oxidase, mutanase, dextranase, glycerol, or combinations thereof. In some embodiments, the active pharmaceutical ingredient is a teeth-bleaching or teeth- whitening agent, including but not limited to carbamide peroxide, sodium bicarbonate, hydrated silica, silicon dioxide, polyvinylpyrrolidone, potassium nitrate, sodium monofluorophosphate, sodium tripolyphosphate, strontium chloride, or combinations thereof. In another embodiment, the active pharmaceutical ingredient is a tooth enamel-enhancing agent. Exemplary tooth enamel enhancing agents include potassium nitrate, strontium acetate, strontium chloride, calcium sodium phosphosilicate, or combinations thereof. In another embodiment, the active pharmaceutical ingredient is an oral anesthetic, including but not limited to benzocaine, lidocaine, clove oil, or combinations thereof. In one embodiment, the active pharmaceutical ingredient is an effervescent including but not limited to sodium bicarbonate, citric acid, tartaric acid, or combinations thereof. Effervescent may be combined with one or more cold, cough, allergy, nasal decongestant, antitussive, expectorant, antihistamine, stimulant, sedative, anti-inflammatory, antibiotic, anti-viral, anti- asthmatic, anti-migraine, hypnotic, narcotic analgesic, or narcotic antagonist active pharmaceutical ingredients, or further combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient is one or more non-steroidal anti-inflammatory drugs (NSAID). Non-limiting examples of NSAID active pharmaceutical ingredients comprise aspirin, ibuprofen, aceclofenac, acemetacin, aloxiprin, azapropazone, benorilate, bromfenac, carprofen, celecoxib, choline magnesium salicylate, diclofenac, diflunisal, etodolac, etoricoxib, faislamine, fenbufen, fenoprofen, flurbiprofen, indometacin, ketoprofen, ketorolac, lornoxicam, loxoprofen, meloxicam, meclofenamic acid, mefenamic acid, meloxicam, metamizole, methyl salicylate, magnesium salicylate, nabumetone, naproxen, nimesulide, oxyphenbutazone, paracetamol, parecoxib, phenylbutazone, piroxicam, salicyl salicylate, sulindac, sulfinpyrazone, suprofen, tenoxicam, tiaprofenic acid, tolmetin, valdecoxib, or combinations thereof. In another embodiment, suitable active pharmaceutical ingredients can comprise analgesics, such as, for example: acetylsalicylic acid, aloxiprin, aminophenazone, anilides, benorilate, benzomorphan derivatives, bezitramide, bucetin, buprenorphine, butorphanol, carbasalate calcium, choline salicylate, codeine, dextromoramide, dextropropoxyphene, dezocine, diamorphine, diflunisal, dihydrocodeine, dihydrocodone, dihydromorphine, diphenylpropylamine derivatives, dipyrocetyl, ethenzamide, fentanyl, floctafenine, flupirtine, glafenine, guacetisal, hydrocodone, hydrocodone bitartrate, hydromorphone, hydromorphone hydrochloride, imidazole salicylate, ketobemidone, metamizole sodium, methadone, morphinan derivatives, morphine, morphine sulphate pentahydrate, morphine-6-glucuronode, morpholine salicylate, nalbuphine, natural opium alkaloids, nefopam, nicomorphine, nifenazone, norhydrocodone, noroxycodone, opioids, opium, oripavine derivatives, oxycodeine, oxycodone, oxycodone hydrochloride, oxymorphone, papaveretum, pentazocine, pethidine, phenacetin, phenazocine, phenazone, phenylpiperidine derivatives, piritramide, potassium salicylate, propacetamol, propyphenazone, pyrazolones, rimazolium, salicylamide, salicylic acid derivatives, salsalate, sodium salicylate, tapentadol, tilidine, tramadol, viminol, ziconotide, or combinations thereof. In another embodiment, the active pharmaceutical ingredient disclosed herein includes an opioid, the opioid is selected from buprenorphine, codeine, dextromoramide, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, morphine, pentazocine, oxycodeine, oxycodone, oxymorphone, norhydrocodone, noroxycodone, morphine-6-glucuronode, tramadol, tapentadol, dihydromorphine, or combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient is a probiotic. Exemplary probiotics include Bifidobacterium infantis 35624, Bifidobacterium lactis HN019, Lactobacillus reuteri ATCC55730, Lactobacillus rhamnosus, Lactobacillus casei DN-114 001, Bifidobacterium lactis Bb-12 or combinations thereof. In another embodiment, the active pharmaceutical ingredient comprises active drug substances used in the treatment of addictive disorders, such as, for example: nicotine, nicotine polacrilex, bupropion, varenicline, disulfiram, calcium carbimide, acamprosate, naltrexone, buprenorphine, methadone, levacetylmethadol, lofexidine, betahistine, cinnarizine, flunarizine, acetylleucine, gangliosides, ganglioside derivatives, tirilazad, riluzole, xaliproden, hydroxybutyric acid, amifampridine, or combinations thereof. In one embodiment described herein, the active pharmaceutical ingredient comprises one or more of nicotine (~2 mg), acesulfame potassium, magnesium oxide, menthol, peppermint oil, xylitol, sodium bicarbonate, sodium carbonate, or combinations thereof. In another embodiment, the active pharmaceutical ingredient can comprise those found in energy drinks, including caffeine, taurine, ginko biloba, glucuronolactone, inositol, niacin, niacinamide, D-pantothenol, panax ginseng root extract, pyridoxine HCl, vitamin B12, cyanocobalamin, riboflavin, guarana, L-carnitine, or combinations thereof. In another embodiment, the pharmaceutical composition can comprise vitamins or minerals. “Vitamins” as used herein refer to nutraceuticals or pharmaceutical ingredients comprising organic substances that are typically considered essential for the normal growth and activity of a subject (e.g., a human or non-human animal patient to whom the composition is to be administered). Non-limiting examples of vitamins include, but are not limited to, vitamin A (retinol), B1 (thiamine), B2 (riboflavin), B complex, B6 (pyridoxine), B12 (cobalamin), C (ascorbic acid), D (cholecalciferol), E (tocopherol), F (linoleic acid), G, H (biotin), and K, and choline, folic acid, inositol, niacin, pantothenic acid, para-aminobenzoic acid or combinations thereof. Vitamins can also include naturally occurring inorganic substances (e.g., minerals) that are typically considered essential for the normal growth and activity of a subject (e.g., a human or non-human animal patient to whom the composition is to be administered). Examples of minerals include, but are not limited to, boron, calcium, chromium, copper, iron, magnesium, manganese, molybdenum, nickel, phosphorus, selenium, silicon, tin, vanadium, or zinc. In some embodiments, the active pharmaceutical ingredient is a pharmaceutical a nutraceutical. Examples of nutraceuticals include, but are not limited to, amino acids, terpenoids (e.g., carotenoid terpenoids and non-carotenoid terpenoids), herbal supplements, homeopathic supplements, glandular supplements, polyphenolics, flavonoid polyphenolics, phenolic acids, curcumin, resveratrol, lignans, glucosinolates, isothiocyanates, indoles, thiosulfinates, phytosterols, anthraquinones, capsaicin, piperine, chlorophyll, betaine, oxalic acid, acetyl-L- carnitine, allantoin, androstenediol, androstendione, betaine (trimethylglycine), caffeine, calcium pyruvate (pyruvic acid), carnitine, carnosine, carotene, carotenoid, choline, chlorogenic acid, cholic acid, chondroitin sulfate, chondroitin sulfate, cholestan, chrysin, coenzyme Q10, conjugated linoleic acid, corosolic acid, creatine, dehydroepiandrosterone, dichlorophen, diindolymethane, dimethylglycine, dimercapto succinic acid, ebselen, ellagic acid, enzymes, fisetin, formononetin, glucaric acid (glucarate), glucosamine (HCl or sulfate), glucosamine (N- acetyl), glutathione, hesperidine, hydroxy-3-methylbutyric acid, 5-hydroxytryptophan, indole-3- carbinol, inositol, isothiocyanates, linolenic acid-gamma, lipoic acid (alpha), melatonin, methylsulfonylmethane, minerals, naringin, pancreatin, para-aminobenzoic acid, paraben (methyl or propyl), phenolics, phosphatidylcholine, phosphatidylserine, phospholipids, phytosterols, progesterone, pregnenolone, omega-3 fatty acids, quercetin, resveratrol, D-ribose, rutin, S- adenosylmethionine, salicylic acid, sulforaphane, tartaric acid, taxifolin, tetrahydropalmatine, theophyline, theobromine, tigogenin, troxerutin, tryptophan, tocotrienol (alpha, beta, and gamma), zeaxanthin, gingko biloba, ginger, cat’s claw, hypericum, aloe vera, evening primrose, garlic, ginseng, capsicum, dong quai, ginseng, feverfew, fenugreek, echinacea, green tea, marshmallow, saw palmetto, tea tree oil, fish oil, psyllium, kava-kava, licorice root, mahonia aquifolium, hawthorne, tumeric, witch hazel, yohimbe, aleurain, mistletoe, bilberry, bee pollen, peppermint oil, beta-carotene, genistein, lutein, lycopene, polyphenols, and the like. Further examples of suitable nutraceuticals include those listed in Handbook of Nutraceuticals and Functional Foods, Robert E. C. Wildman, Ed., CRC Press (2001), which is incorporated by reference herein for the teachings related to nutraceuticals. Other useful pharmaceutical ingredients or nutraceuticals that can be included as an active ingredient include fish oils, egg oils, squid oils, krill oils, nut oils, seed oils; soy oils, avocado oils, seabuckthorn seed or berry oils, clary sage seed oils, algal oils, flaxseed oils, sacha ichi oils, echium oils, hemp oils, omega-3 fatty acids, polyunsaturated omega-3 fatty acids, hexadecatrienoic acid (HTA), alpha-linolenic acid (ALA), stearidonic acid (SDA), eicosatrienoic acid (ETE), eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA, timnodonic acid), heneicosapentaenoic acid (HPA), docosapentaenoic acid (DPA), clupanodonic acid), docosahexaenoic acid (DHA, cervonic acid), tetracosapentaenoic acid, tetracosahexaenoic acid (nisinic acid), and free acids, etheyl esters, or other esters or salts thereof. In one aspect, the pharmaceutical ingredient is a highly purified omega-3 fatty acid, ester, or salt thereof. In one embodiment described herein, an active pharmaceutical ingredient is the only active ingredient in the pharmaceutical composition. In another embodiment, the active ingredient or drug can be an active pharmaceutical ingredient, derivatives thereof, or combinations thereof. In one embodiment, the pharmaceutical compositions as described herein are suitable for use for water soluble as well as slightly soluble or insoluble active drug substances. In another embodiment, the pharmaceutical compositions described herein may comprise pharmaceutically acceptable salts of any of the above-mentioned active drug substances. The term “pharmaceutically acceptable salts” of an active pharmaceutical ingredient includes alkali metal salts such as, for example, sodium or potassium salts, alkaline earth metal salts such as, for example, calcium and magnesium salts, and salts with organic or inorganic acid such as, for example, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, maleic acid, succinic acid, tartaric acid, methanesulphonic acid, toluenesulphonic acid etc. In another embodiment, the active pharmaceutical ingredient may also be in the form of pharmaceutically acceptable salts, uncharged or charged molecules, molecular complexes, solvates, or anhydrates thereof, and, if relevant, single isomers, enantiomers, racemic mixtures, or mixtures thereof. In another embodiment, the active pharmaceutical ingredient may be in any of its crystalline, polymorphous, semi-crystalline, amorphous, or polyamorphous forms or mixtures thereof. In one embodiment described herein, the ratio of the active ingredient or drug to the total matrix fill, e.g., matrix fill ingredient(s) and active pharmaceutical ingredient(s), can be from about 1:50 to about 1:1 by weight, including all ratios in the specified range. In another embodiment described herein, the active ingredient to total matrix fill ratio can also be from about 1:16 to about 1:1 by weight, including all ratios in the specified range. The active ingredient to total matrix fill ratio can also be about 1:16; about 1:9; about 1:3; about 1:2; or about 1:1 including all ratios in the specified range. In one embodiment described herein, the active ingredient or drug comprises from about 5% to about 80% of the matrix fill mass including all iterations of integers within the specified range. In one aspect described herein, the active ingredient or drug comprises about 80% of the matrix fill mass. In another aspect, the active ingredient or drug comprises about 60% of the matrix fill mass. In another aspect, the active ingredient or drug comprises about 40% of the matrix fill mass. In another aspect, the active ingredient or drug comprises about 6% of the matrix fill mass. In another embodiment described herein, the active ingredient or drug comprises about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, about 15%, about 10%, about 5%, about 2%, or about 1% of the matrix fill mass. In one embodiment described herein, the weight ratio range of the active pharmaceutical ingredient to the matrix fill mass is about 1:20 to about 10:1. In one aspect, the weight ratio of the active pharmaceutical ingredient to the matrix fill mass is about 1:3. In another aspect, the weight ratio of the active pharmaceutical ingredient to the matrix fill mass is about 1:9. In another aspect, the weight ratio of the active pharmaceutical ingredient to the matrix fill mass is about 1:17. In some embodiments, one or more active pharmaceutical ingredients may be incorporated into a softgel capsule as described herein. In one embodiment, the composition described herein can provide a dosage of an active ingredient for administration. The dosage form can be administered, for example, to a subject, or a subject in need thereof. In one aspect, the subject may be a mammal, or a mammal in need thereof. In another aspect, the dosage form can be administered, for example, to a human or a human in need thereof. In another aspect, the human subject or a human subject in need thereof is a medical patient. In one embodiment, the pharmaceutical composition described herein comprises an active pharmaceutical ingredient of about 0.01 mg to about 2000 mg, including all integers within the specified range. In one aspect, the active pharmaceutical ingredient is about 0.01 mg, 0.05 mg, 0.1 mg, 0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, about 1320 mg, about 1330 mg, about 1340 mg, about 1350 mg, about 1360 mg, about 1370 mg, about 1380 mg, about 1390 mg, about 1400 mg, about 1410 mg, about 1420 mg, about 1430 mg, about 1440 mg, about 1450 mg, about 1460 mg, about 1470 mg, about 1480 mg, about 1490 mg, about 1500 mg, about 1510 mg, about 1520 mg, about 1530 mg, about 1540 mg, about 1550 mg, about 1560 mg, about 1570 mg, about 1580 mg, about 1590 mg, about 1600 mg, about 1610 mg, about 1620 mg, about 1630 mg, about 1640 mg, about 1650 mg, about 1660 mg, about 1670 mg, about 1680 mg, about 1690 mg, about 1700 mg, about 1710 mg, about 1720 mg, about 1730 mg, about 1740 mg, about 1750 mg, about 1760 mg, about 1770 mg, about 1780 mg, about 1790 mg, about 1800 mg, about 1810 mg, about 1820 mg, about 1830 mg, about 1840 mg, about 1850 mg, about 1860 mg, about 1870 mg, about 1880 mg, about 1890 mg, about 1900 mg, about 1910 mg, about 1920 mg, about 1930 mg, about 1940 mg, about 1950 mg, about 1960 mg, about 1970 mg, about 1980 mg, about 1990 mg, about 2000 mg, or even more. Methods of Manufacturing In one aspect, softgel capsules are made using a rotary die apparatus as described in U.S. Patent Nos. 5,459,983; 5,146,730; and 6,482,516, each of which are incorporated by reference herein for such teachings. Another embodiment described herein includes a process of manufacturing softgel capsules comprising the methods as described herein. The process includes preparing a gel mass composition comprising a film-forming, water-soluble polymer, one or more precipitation inhibitors, an appropriate plasticizer or co-solvent, and solvent; casting the gel mass into films or ribbons using heat-controlled drums or surfaces; and manufacturing a soft capsule comprising a matrix fill using rotary die technology. Optionally, one or more antifoaming agents may be incorporated to suppress foam during the preparation of the gels. Example amounts of antifoaming agent(s) in relation to different amounts precipitation inhibitor are shown in Table 10. In one embodiment, the preparation of precipitation inhibitor softgel capsules involves first dissolving the precipitation inhibitor in an aqueous solution. This solution is subsequently mixed with one or more plasticizers and blended with gelatin to yield a final uniform gel mass. In another embodiment, the preparation and manufacture of precipitation inhibitor softgel capsules involves dissolving the precipitation inhibitor in an aqueous solution, followed by the addition of one or more alkali-neutralizing agent such as ammonia, sodium hydroxide, potassium hydroxide, or liquid amines such as tri-ethanol amine or ethylene diamine. The amount of alkali is adjusted to give a final pH between 5.0 to 8.0. In another embodiment, the final pH does not exceed 7.0. This solution is subsequently mixed with one or more plasticizers and blended with gelatin to yield a final uniform gel mass. The precipitation inhibitor softgel capsules are typically made using a rotary die process. The rotary die production process used to manufacture soft gelatin capsules works by leading two gel ribbons over a heated wedge into the heated pockets of the two rotating dies while injecting a liquid film into the capsule formed by the rotating dies. For this production process, the gelatin needs to have the viscoelastic properties necessary to flow at 56 °C, form a strong thick ribbon when cooled to 15 °C, and produce a robust seam when encapsulating the fill material. For example, precipitation inhibitor softgel capsule gel masses exhibit the desired flow characteristics at both 56 °C and at 15 °C. The thickness of the films or ribbons that form the soft capsule shell comprises from about 0.010 inches (≈0.254 mm) to about 0.050 inches (≈1.27 mm), including all integers within the specified range. The shell thickness can be about 0.010 inch (≈0.254 mm), about 0.015 inch (≈0.381 mm), about 0.02 in (≈0.508 mm), about 0.03 in (≈0.762 mm), about 0.04 in (≈1.02 mm), or about 0.05 in (≈1.27 mm). In one embodiment, the thickness comprises from about 0.02 inches (≈0.508 mm) to about 0.040 inches (≈1.02 mm). In one embodiment, the shell thickness is about 0.028 inches (≈0.711 mm). In another embodiment, the shell thickness is about 0.033 inches (≈0.838 mm). In another embodiment, the shell thickness is about 0.038 inches (≈0.965 mm). In one embodiment described herein, the soft capsule shell described herein, encapsulates a matrix fill as described herein. In another embodiment described herein, the soft capsule shell and encapsulated matrix fill comprises an outer dimension from about 2 oval to about 30 oval including all iterations of capsule size within the specified range (e.g., 2 oval, 3 oval, 4 oval, 5 oval, 6 oval, 7 oval, 8 oval, 10 oval, 12 oval, 16 oval, 20, or 30 oval). In another embodiment described herein, the soft capsule shell and encapsulated matrix fill comprises an outer dimension from about 2 round to about 28 round including all iterations of capsule size within the specified range (e.g., 2 round, 3 round, 4 round, 5 round, 6 round, 7 round, 8 round, 10 round, 12 round, 16 round, 20 round or 28 round). In another embodiment described herein, the soft capsule shell and encapsulated matrix fill comprises an outer dimension from about 2 oblong to about 22 oblong including all iterations of capsule size within the specified range (e.g., 2 oblong, 3 oblong, 4 oblong, 5 oblong, 6 oblong, 7 oblong, 8 oblong, 10 oblong, 11, oblong, 12 oblong, 14 oblong, 16 oblong, 20 oblong, or 22 oblong). Dimension specifications of soft capsules and tablets are known to those skilled in the art. See Remington’s Essentials of Pharmaceutics, Pharmaceutical Press Publishing Company, London, UK, 1stEdition, 2013, which is incorporated by reference herein for such teachings. In one non-limiting exemplary embodiment, the soft capsule can be manufactured by the following steps: (a) preparing a gel mass composition comprising one or more film-forming polymers, one or more precipitation inhibitors, one or more plasticizers or co-solvents, and one or more solvents to form a gel mass, optional use of one or more anti-foaming agents; (b) heating the gel mass at 57–80 °C under vacuum for 15–30 min to create a homogenous and de-aerated gel mass; (c) ageing the homogenous and de-aerated gel mass 12–96 hr at 50–60 °C to create an aged gel mass; (d) casting the aged gel mass into films or ribbons using heat-controlled drums or surfaces; (e) transferring a homogenized fill solution to an encapsulation line; (f) encapsulating the homogenized fill solution within the gel mass films or ribbons using rotary dye encapsulation to create a capsule; (g) drying and finishing the capsule; (h) optionally, printing identification on the capsule; (i) optionally, coating the capsule with a coating and drying; and (j) post processing and packaging. Additional processing aids that can be used during the manufacturing process are shown in Table 3. Nitrogen is used to purge oxygen from the gel mass. Medium chain triglycerides and lecithin are used as lubricants to prevent the gel ribbon from sticking to the spreader box and rotary die encapsulation machinery. Capsules are also lubricated to prevent sticking during post- manufacturing processing. Table 3. Exemplary Processing Aids Component Function Mass Range (mg) Nitrogen Oxygen purge – Medium Chain Triglycerides (MCT) Gelatin Ribbon Lubricant Trace 97% MCT & 3% Lecithin Capsule Lubricant Trace When softgel capsules are manufactured they are typically dried for a period of time. This permits water to evaporate from the capsule shell to increase rigidity and strength. A range of about 5–30% by mass of water from the shell can evaporate. Consequently, the relative mass percentages of the other shell components increase as water is lost to evaporation. In addition, when fills with low water are encapsulated, water from the capsule shell can migrate from the shell into the fill via osmosis. This can also contribute to water loss from the shell. Table 4 shows the estimated masses of the fill, shell, and total capsule immediately after manufacturing and after drying (for an oil-filled capsule). Table 4. Finished Capsule Target Composition Capsule Components Mass (mg)* Total fill weight (prior to drying) 1000 Total shell weight (prior to drying) 635 Total capsule weight (prior to drying) 1635 Total fill weight (after drying) 1000 Total shell weight (after drying) 440 Total capsule weight (after drying) 1440 Mass percent difference in fill after drying 0% Mass percent difference in shell after drying 30% Mass percent difference in total capsule after drying 12% * Estimated based on capsules from a prototype batch with the assumption: 20-oblong die (wet shell 635mg, dry shell 440mg) In some embodiments, rapid releasing softgel capsules may also be pre-stressed to enhance the release rate. Exemplary examples of pre-stressing including laser drilling, mechanical drilling, scoring, or other known means to pre-stress the gel capsule. In one embodiment, rapid releasing softgel capsules may be pre-stressed by laser drilling or other known means during manufacturing, regardless of the particular softgel capsule formulation or the fill formulation. In other embodiments, rapid releasing softgel capsules may be pre-stressed during manufacturing with a particular softgel capsule formulation as described herein. Methods of Administration The dosage form can be administered, for example, 1×, 2×, 3×, 4×, 5×, 6× per day, or even more. One or more dosage forms can be administered, for example, for 1, 2, 3, 4, 5, 6, 7 days, or even longer. One or more dosage forms can be administered, for example, for 1, 2, 3, 4 weeks, or even longer. One or more dosage forms can be administered, for example, for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months, or even longer. One or more dosage forms can be administered until the patient, subject, mammal, mammal in need thereof, human, or human in need thereof, does not require treatment, prophylaxis, or amelioration of any disease or condition. The dosage form can be administered quaque die (QD), bis in die (BID), ter in die (TID), quater in die (QID) or in other dosing regimens, such as X capsules every Y hours, where X is the number of capsules and Y is the hourly interval. In one embodiment, the dosage form described herein is administered in multiple doses simultaneously. For example, two or more identical doses are administered at one time. In another embodiment, two or more different doses are administered at one time. Such dual or different simultaneous doses can be used to provide an effective amount of the pharmaceutical composition to a subject in need thereof. In another embodiment, the dosage forms as described herein can be administered with or without food. In one aspect, the dosage forms as described herein can be administered with food. In another aspect, the dosage forms as described herein can be administered without food. Kits and Packaging Another embodiment described herein is a kit for dispensing an oral pharmaceutical composition comprising at least one rapid releasing soft capsule and at least one receptacle comprising a tamper evident, moisture proof packaging comprising blister or strip packs, aluminum blister, transparent or opaque polymer blister with pouch, polypropylene tubes, colored blister materials, tubes, bottles, and bottles optionally containing a child-resistant feature, optionally comprising a desiccant, such as a molecular sieve or silica gel; and optionally, an insert comprising instructions or prescribing information for the active pharmaceutical ingredient. In one aspect, the tamper evident packaging comprises: bottles, film wrappers, blister or strip packs, bubble packs, heat shrink bands or wrappers, foil, paper, or plastic pouches, container mouth inner seals, tape seals, breakable caps, sealed metal tubes or plastic heat-sealed tubes, sealed cartons, aerosol containers, cans including metal and composite materials, or any combination thereof. The packaging may also contain a label, appropriate instructions for prescribing, instructions for use, warnings, or other appropriate information. In some embodiments, packaging may comprise the use of bottles and / or blisters having moisture barrier properties. In one aspect, high density polyethylene (HDPE) or aluminum bottles having moisture barrier properties may be used for packaging kits comprising softgel capsules as described herein. In some embodiments, packaging may further comprise the use of a desiccant. In one aspect, the dessicant may comprise a silica gel package, which is typically provided as a 1-gram packet. The use of dessicants and bottles and blisters having moisture barrier properties in packaging can help prevent the aggregation and nesting of softgels. One embodiment described herein is a precipitation inhibitor softgel capsule formulation, the formulation comprising: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. In one aspect, the one or more film-forming polymers comprises gelatin, gelatin hydrolysates, collagen, carrageenans, or agars. In another aspect, the one or more film-forming polymers comprises gelatin having a Bloom value of about 50 Bloom to about 300 Bloom. In another aspect, the gelatin has a Bloom value of about 150 Bloom. In another aspect, the formulation comprises about 20–40% by mass of the one or more film-forming polymers. In another aspect, the one or more precipitation inhibitors comprise one or more of polyvinylpyrrolidone, polyvinyl acetate phthalate, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer, poloxamers, polymethylmethacrylates, cellulose acetate phthalate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, derivatives thereof, or combinations thereof. In another aspect, the formulation comprises about 0.1–10% by mass of the one or more precipitation inhibitors. In another aspect, the formulation comprises about 1–8% by mass of the one or more precipitation inhibitors. In another aspect, the formulation comprises about 2.5–5% by mass of the one or more precipitation inhibitors. In another aspect, the one or more plasticizers or co-solvents comprises solutions of polyols, monosaccharides, disaccharides, oligosaccharides, blended hydrophilic molecules, glycerol, sorbitol, polyethylene glycols, or maltitol. In another aspect, the formulation comprises about 10–20% by mass of the one or more plasticizers or co-solvents. In another aspect, the one or more neutralization agents comprises NH4OH, NaOH, KOH, or combinations thereof. In another aspect, the formulation comprises about 0.1–0.5% by mass of the one or more neutralization agents. In another aspect, the one or more solvents comprises water. In another aspect, the formulation further comprises one or more of colorants, opacifiers, flavors or sweeteners, humectants, preservatives, coatings, viscosity modifiers, fillers or bulking agents, active pharmaceutical ingredients, or buffering salts and acids. In another aspect, the formulation comprises about 0.01–10% by mass of one or more colorants comprising synthetic dyes, natural dyes, or a combination thereof. In another aspect, the formulation comprises about 0.01–1% by mass of one or more opacifiers comprising titanium dioxide, zinc oxide, iron oxide, calcium carbonate, or combinations thereof. In another aspect, the formulation comprises about 0.01–1% by mass of one or more flavors or sweeteners. In another aspect, the capsule immediately releases at 37 °C at pH 1.2–7 and delivers the precipitation inhibitor into the medium. In another aspect, the capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7. Another embodiment described herein is a method for manufacturing a precipitation inhibitor softgel capsule, the method comprising: (a) preparing a gel mass composition comprising one or more film-forming polymers, one or more precipitation inhibitors, one or more plasticizers or co-solvents, and one or more solvents to form a gel mass; (b) heating the gel mass to create a homogenous and de-aerated gel mass; (c) ageing the homogenous and de-aerated gel mass to create an aged gel mass; (d) casting the aged gel mass into films or ribbons using heat- controlled drums or surfaces; (e) transferring a homogenized fill solution to an encapsulation line; (f) encapsulating the homogenized fill solution within the gel mass films or ribbons using rotary dye encapsulation to create a capsule; (g) drying and finishing the capsule; (h) optionally, printing identification on the capsule; (i) optionally, coating the capsule with a coating and drying; and (j) post processing and packaging. In another aspect, the gel mass comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. In another aspect, heating the gel mass in step (b) comprises a temperature of about 57–80 °C under vacuum for about 15–30 minutes to create the homogenous and de-aerated gel mass. In another aspect, ageing the homogenous and de-aerated gel mass in step (c) comprises a temperature of about 50–60 °C for about 12–96 hours to create the aged gel mass. A precipitation inhibitor softgel capsule manufactured by the methods described herein. Another embodiment described herein is a pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7 and releases the precipitation inhibitor and the one or more B BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250. In one aspect, the precipitation inhibitor softgel capsule comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. Another embodiment described herein is a method for administering one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to a subject in need thereof, the method comprising administering to the subject a pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising the one or more BCS Class II APIs, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes following administration and releases the precipitation inhibitor and the matrix fill comprising the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to the subject, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250. In one aspect, the precipitation inhibitor softgel capsule comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. It will be apparent to one of ordinary skill in the relevant art that suitable modifications and adaptations to the compositions, formulations, methods, processes, and applications described herein can be made without departing from the scope of any embodiments or aspects thereof. The compositions and methods provided are exemplary and are not intended to limit the scope of any of the specified embodiments. All of the various embodiments, aspects, and options disclosed herein can be combined in any variations or iterations. The scope of the compositions, formulations, methods, and processes described herein include all actual or potential combinations of embodiments, aspects, options, examples, and preferences herein described. The exemplary compositions and formulations described herein may omit any component, substitute any component disclosed herein, or include any component disclosed elsewhere herein. The ratios of the mass of any component of any of the compositions or formulations disclosed herein to the mass of any other component in the formulation or to the total mass of the other components in the formulation are hereby disclosed as if they were expressly disclosed. Should the meaning of any terms in any of the patents or publications incorporated by reference conflict with the meaning of the terms used in this disclosure, the meanings of the terms or phrases in this disclosure are controlling. Furthermore, the foregoing discussion discloses and describes merely exemplary embodiments. All patents and publications cited herein are incorporated by reference herein for the specific teachings thereof. Various embodiments and aspects of the inventions described herein are summarized by the following clauses: Clause 1. A precipitation inhibitor softgel capsule formulation, the formulation comprising: about 15–40% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. Clause 2. The formulation of clause 1, wherein the one or more film-forming polymers comprises gelatin, gelatin hydrolysates, collagen, carrageenans, or agars. Clause 3. The formulation of clause 1 or 2, wherein the one or more film-forming polymers comprises gelatin having a Bloom value of about 50 Bloom to about 300 Bloom. Clause 4. The formulation of any one of clauses 1–3, wherein the gelatin has a Bloom value of about 150 Bloom. Clause 5. The formulation of any one of clauses 1–4, wherein the formulation comprises about 20–40% by mass of the one or more film-forming polymers. Clause 6. The formulation of any one of clauses 1–5, wherein the one or more precipitation inhibitors comprise one or more of polyvinylpyrrolidone, polyvinyl acetate phthalate, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft co-polymer, poloxamers, polymethylmethacrylates, cellulose acetate phthalate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, derivatives thereof, or combinations thereof. Clause 7. The formulation of any one of clauses 1–6, wherein the formulation comprises about 0.1–10% by mass of the one or more precipitation inhibitors. Clause 8. The formulation of any one of clauses 1–7, wherein the formulation comprises about 1–8% by mass of the one or more precipitation inhibitors. Clause 9. The formulation of any one of clauses 1–8, wherein the formulation comprises about 2.5–5% by mass of the one or more precipitation inhibitors. Clause 10. The formulation of any one of clauses 1–9, wherein the one or more plasticizers or co-solvents comprises solutions of polyols, monosaccharides, disaccharides, oligosaccharides, blended hydrophilic molecules, glycerol, sorbitol, polyethylene glycols, or maltitol. Clause 11. The formulation of any one of clauses 1–10, wherein the formulation comprises about 10–20% by mass of the one or more plasticizers or co-solvents. Clause 12. The formulation of any one of clauses 1–11, wherein the one or more neutralization agents comprises NH4OH, NaOH, KOH, or combinations thereof. Clause 13. The formulation of any one of clauses 1–12, wherein the formulation comprises about 0.1–0.5% by mass of the one or more neutralization agents. Clause 14. The formulation of any one of clauses 1–13, wherein the one or more solvents comprises water. Clause 15. The formulation of any one of clauses 1–14, further comprising one or more of colorants, opacifiers, flavors or sweeteners, humectants, preservatives, coatings, viscosity modifiers, fillers or bulking agents, active pharmaceutical ingredients, or buffering salts and acids. Clause 16. The formulation of any one of clauses 1–15, wherein the formulation comprises about 0.01–10% by mass of one or more colorants comprising synthetic dyes, natural dyes, or a combination thereof. Clause 17. The formulation of any one of clauses 1–16, wherein the formulation comprises about 0.01–1% by mass of one or more opacifiers comprising titanium dioxide, zinc oxide, iron oxide, calcium carbonate, or combinations thereof. Clause 18. The formulation of any one of clauses 1–17, wherein the formulation comprises about 0.01–1% by mass of one or more flavors or sweeteners. Clause 19. The formulation of any one of clauses 1–18, wherein the capsule immediately releases at 37 °C at pH 1.2–7 and delivers the precipitation inhibitor into the medium. Clause 20. The formulation of any one of clauses 1–19, wherein the capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7. Clause 21. A method for manufacturing a precipitation inhibitor softgel capsule, the method comprising: (a) preparing a gel mass composition comprising one or more film-forming polymers, one or more precipitation inhibitors, one or more plasticizers or co-solvents, and one or more solvents to form a gel mass; (b) heating the gel mass to create a homogenous and de-aerated gel mass; (c) ageing the homogenous and de-aerated gel mass to create an aged gel mass; (d) casting the aged gel mass into films or ribbons using heat-controlled drums or surfaces; (e) transferring a homogenized fill solution to an encapsulation line; (f) encapsulating the homogenized fill solution within the gel mass films or ribbons using rotary dye encapsulation to create a capsule; (g) drying and finishing the capsule; (h) optionally, printing identification on the capsule; (i) optionally, coating the capsule with a coating and drying; and (j) post processing and packaging. Clause 22. The method of clause 21, wherein the gel mass comprises: about 15–40% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. Clause 23. The method of clause 21 or 23, wherein heating the gel mass in step (b) comprises a temperature of about 57–80 °C under vacuum for about 15–30 minutes to create the homogenous and de-aerated gel mass. Clause 24. The method of any one of clauses 21–23, wherein ageing the homogenous and de-aerated gel mass in step (c) comprises a temperature of about 50–60 °C for about 12– 96 hours to create the aged gel mass. Clause 25. A precipitation inhibitor softgel capsule manufactured by the method of any one of clauses 21–24. Clause 26. A pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7 and releases the precipitation inhibitor and the one or more B BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250. Clause 27. The pharmaceutical dosage form of clause 26, wherein the precipitation inhibitor softgel capsule comprises: about 15–40% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. Clause 28. A method for administering one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to a subject in need thereof, the method comprising administering to the subject a pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising the one or more BCS Class II APIs, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes following administration and releases the precipitation inhibitor and the matrix fill comprising the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to the subject, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250. Clause 29. The method of clause 28, wherein the precipitation inhibitor softgel capsule comprises: about 15–40% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents. Clause 30. The formulation or pharmaceutical dosage form of any previous clause, wherein the formulation or pharmaceutical dosage form comprises about 0.1-1% by mass of one or more antifoaming agents. Clause 31. The method of any previous clause, wherein the method comprising: adding about 0.1-1% by mass of the one or more antifoaming agents to the precipitation inhibitor softgel capsule during its preparation process to suppress foam formed when mixing one or more plasticizers or co-solvents. Clause 32. A precipitation inhibitor softgel capsule formulation, the formulation comprising: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents.

[0002] EXAMPLES Example 1 Exemplary precipitation inhibitors used in this study are shown in Table 5. Table 5. Exemplary Precipitation Inhibitors Compound MolecularWeight (kDa)Brand Name ManufacturerPolyvinylpyrrolidone 2–3 Kollidon® 12PF BASF Polyvinylpyrrolidone 44–54 Kollidon® 30 BASF Polyvinylpyrrolidone 900–1200 Kollidon® 90F BASF Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co- 90–140 Soluplus® BASF polymer Poloxamer, copolymer of ethylene Kolliphor® P 407 oxide and propylene oxide4GeismarBASFHydroxypropylcellulose Klucel™ LF PH Ashland Hydroxyethylcellulose Natrosol™ 250 L PH Ashland hydroxypropyl-methylcellulose 200 Benecel™ 250 L PH Ashland Preparation of Precipitation Inhibitor Solutions The preparation of precipitation inhibitor solutions involved the initial dissolution of the precipitation inhibitor in a solvent such as water, or water combined with glycerol (if required, antifoaming agent), sorbitol, or other low molecular weight alcohols or polyols. The detailed formulation process started with the preparation of an aqueous precipitation inhibitor solution in a sealable glass container. The desired amount of precipitation inhibitor was dissolved in approximately 37 mL of water under continuous stirring to ensure uniform dissolution. To minimize water evaporation, the glass container was sealed during the stirring process, which was conducted using an overhead stirrer equipped with a cap featuring an opening for access. The solution was visually inspected for the presence of any precipitate. In the case of a cloudy solution, an upright microscope was employed for closer examination. The pH of the precipitation inhibitor solution was maintained within the range of 5 to 7 to prevent denaturation of the gelatin polymer. The pH was monitored using pH paper and adjusted, as necessary, to fall within this specified range. Adjustments were made using a solution of NaOH with a concentration of 0.5 M. Additionally, alternative bases such as ammonia, potassium hydroxide, or liquid amines such as tri-ethanolamine or ethylene diamine can be employed for the same purpose. Precipitation inhibitor solutions are shown in Table 6. Table 6. Precipitation Inhibitor Solutions Precipitation Inhibitor PI (% Water (% pH at PI NaOH added to (PI) mass) mass) Dissolution adjust pH (mmol) Kollidon® 12PF 6.4 93.6 5.0 – Kollidon® 30 6.4 93.6 4.0 Kollidon® 90F 6.4 93.6 5.5 – Soluplus® 6.4 93.6 5.0 – Kolliphor® P 407 Geismar 6.4 93.6 6.0 – Klucel™ LF PH 6.4 93.6 5.0 – Natrosol™ 250 L PH 6.4 93.6 6.0 – Benecel™ 250 L PH 6.4 93.6 6.0 – Kollidon® 12PF 12.0 88.0 5.0 – Kollidon® 30 12.0 88.0 4.0 0.1 Kollidon® 90F 12.0 88.0 6.0 – Soluplus® 12.0 88.0 5.0 – Kolliphor® P 407 Geismar 12.0 88.0 6.0 – Klucel™ LF PH 12.0 88.0 6.0 – Natrosol™ 250 L PH 12.0 88.0 6.0 – Benecel™ 250 L PH 12.0 88.0 – – Example 2 Preparation of Precipitation Inhibitor Softgel Formulations The precipitation inhibitor softgel formulation preparation process involved the incorporation of glycerol, and if required, antifoaming agent, into the aqueous precipitation inhibitor solution under continuous stirring. Following a 5-min stirring period, the mixture was heated in a water bath until it reached a temperature of 70 °C. At this point, gelatin was added to the heated mixture and stirred for a duration ranging from 0.5 to 2 hours to facilitate gelatin cooking. To eliminate any entrapped air bubbles within the gel mass, the gel was subjected to overnight deaeration at 70 °C. After the deaeration process, the precipitation inhibitor softgel capsule gel mass was visually inspected to assess its attributes, including clarity, the presence of particles, and the absence of air bubbles. Subsequently, the temperature of the precipitation inhibitor softgel capsule gel mass was lowered to 56 °C, and the precipitation inhibitor softgel capsule gel mass was allowed to equilibrate for approximately 1 day prior to rheological characterization. Formulations of precipitation inhibitor softgel gel masses are shown in Table 7. Table 7. Precipitation Inhibitor Softgel Mass Compositions Precipitation InhibitorPI (% maGlycerol (% Water (% Gelatin (% (PI)ss)mass) mass) mass) Kollidon® 12PF 2.5 19.5 35.7 42.3 Kollidon® 30 2.5 19.5 35.7 42.3 Kollidon® 90F 2.5 19.5 35.7 42.3 Soluplus® 2.5 19.5 35.7 42.3 Kolliphor® P 407 Geismar 2.5 19.5 35.7 42.3 Klucel™ LF PH 2.5 19.5 35.7 42.3 Natrosol™ 250 L PH 2.5 19.5 35.7 42.3 Benecel™ 250 L PH 2.5 19.5 35.7 42.3 Kollidon® 12PF 4.8 19.1 34.8 41.3 Kollidon® 30 4.8 19.1 34.8 41.3 Kollidon® 90F 4.8 19.1 34.8 41.3 Soluplus® 4.8 19.1 34.8 41.3 Kolliphor® P 407 Geismar 4.8 19.0 34.9 41.3 Klucel™ LF PH 4.8 19.2 34.4 41.6 Natrosol™ 250 L PH 4.8 19.1 34.8 41.3 Example 3 Rheological Characterization The rheological properties of the precipitation inhibitor softgel capsule gel masses were investigated using an Anton Paar Physica MCR 301 rheometer. The precipitation inhibitors evaluated were Kollidon® 12PF, Kollidon® 30, Kollidon® 90F, Klucel™, Natrosol™, Soluplus®, and Kolliphor® P 407 Geismar, each incorporated into the gel mass at concentrations of approximately 2.5% and 5.0% by mass. To simulate the rotary die production of soft capsules, the rheological properties were determined under a controlled oscillatory shear strain (1 Hz) and a controlled strain (deformation) of 1% during a temperature sweep measurement from 56 °C to 15 °C. A parallel plate geometry was employed to apply the shear to the molten gel mass. The sample preparation and measurement procedure started by heating the gel mass sample to 56 °C and subsequently loaded onto the rheometer at that temperature. Following a 1-min equilibration period at 56 °C (1 °C / min), the measurement commenced. The gel sample was then cooled to 15 °C at a rate of 30 °C / min. Upon reaching 15 °C, the measurement continued for an additional 15 min (1 °C / min) at the isothermal condition. The rheological properties of the gel mass samples included the gelation point, the gel strength (G′) at 15 °C, and the loss factor (G″ / G′) at 15 °C. See Table 8A and FIG.1A–B. Table 8A. Precipitation Inhibitor Gel Mass Properties Complex Gel Loss Precipitation Inhibitor PI (% Viscosity Gelation Strength Factor (PI) mass) (mPa·s) at Point (°C) (G′) (Pa × (G″ / G′) 56 °C 105) at 15 °C at 15 °C Control (typical softgel capsule)None 19,514 ± 81 30.00 1.18 ± 0.04 0.07Kollidon® 12PF 2.4 23,552 ± 182 30.50 1.20 ± 0.04 0.07 Kollidon® 30 2.4 33,845 ± 294 31.14 1.27 ± 0.04 0.07 Kollidon® 90F 2.4 27,123 ± 51 30.36 1.14 ± 0.03 0.07 Soluplus® 2.5 21,803 ± 212 30.32 1.17 ± 0.03 0.09 Kolliphor® P 407 Geismar 2.5 23,944 ± 68 29.77 1.10 ± 0.03 0.09 Klucel™ LF PH 2.4 13,738 ± 103 29.57 1.04 ± 0.03 0.07 Natrosol™ 250 L PH 2.4 25,937 ± 260 30.58 1.14 ± 0.03 0.08 Kollidon® 12PF 4.8 29,906 ± 188 30.73 1.07 ± 0.03 0.07 Kollidon® 30 4.8 38,282 ± 354 31.30 1.10 ± 0.03 0.08 Kollidon® 90F 4.8 62,071 ± 656 31.59 1.17 ± 0.04 0.08 Soluplus® 4.8 22,070 ± 270 29.90 1.09 ± 0.03 0.11 Kolliphor® P 407 Geismar 4.8 89,195 ± 734 31.16 1.12 ± 0.03 0.11 Klucel™ LF PH 4.8 27,206 ± 294 30.12 1.06 ± 0.03 0.09 Natrosol™ 250 L PH 4.8 48,030 ± 551 30.91 1.20 ± 0.04 0.09 Further example properties of the gel mass samples at different PI (% mass) are shown in Table 8B, which include gelation point, gel G′ at 15 °C, and G″ / G′ at 15 °C. Complex viscosity (mPa·s) at 56 °C is consistent with the data presented in Table 8A, though it is not shown in Table 8B. Table 8B : Properties of gel mass with different PI and corresponding % mass. Precipitation PI (% Gelation Gel Strength (Gʹ) Loss Factor Kollidon® 12PF 2.4 30.50 1.20 ± 0.04 0.07 4.8 30.73 1.07 ± 0.03 0.07 7.0 30.00 1.64 ± 0.05 0.08 9.0 29.48 1.48 ± 0.05 0.08 Precipitation Inhibitor Soft Gel Swatch Disintegration Study To evaluate the disintegration properties of softgel capsules comprising precipitation inhibitor in conditions analogous to the pH of the lower stomach, 30 mg get swatch samples from Example 3 (2.5 and 5.0% by mass precipitation inhibitor) were submerged in 50 mL of 0.1 M HCl (pH ~ 1) at 37 °C for 30 min. The complete dissolution of the gel materials was visually monitored and timed using a stopwatch. This experiment simulates the acidic conditions of the lower stomach, where precipitation inhibitor soft gel capsules are expected to disintegrate and release the precipitation inhibitor. The solubilized precipitation inhibitor can then prevent precipitation in the alkaline environment of the duodenum and intestine where API precipitation typically occurs. Results are shown in Table 9 and FIG.1. Table 9. Precipitation Inhibitor Soft Gel Swatch Disintegration Time Precipitation Inhibitor (PI) Disintegration Time (min) Control (No PI; typical softgel capsule) 2 ~2.5% mass PI Kollidon® 12PF 1 Kollidon® 30 2 Kollidon® 90F 5 Soluplus® 2 Kolliphor® P 407 Geismar 3 Klucel™ LF PH 2 Natrosol™ 250 L PH 3 ~5% mass PI Kollidon® 12PF 4 Kollidon® 30 2 Kollidon® 90F 4 Soluplus® 3 Kolliphor® P 407 Geismar 3 Klucel™ LF PH 7 Natrosol™ 250 L PH 1 Example 5 The precipitation inhibitor softgel formulation was prepared by incorporating glycerol into an aqueous solution under continuous stirring, followed by heating to 70 °C. If required, antifoaming agent may be added as shown in Table 10. Gelatin was then added, and the mixture was stirred for 0.5 to 2 hours. The gel was deaerated overnight at 70 °C to remove air bubbles, then inspected for clarity, particles, and bubble-free consistency. The temperature was lowered to 56 °C, and the gel mass was equilibrated for one day before rheological characterization. Formulations of precipitation inhibitor softgel gel masses are shown in Table 10. Some exemplary ranges of the formulations are shown in Table 11. Table 10: Precipitation Inhibitor Softgel Mass Composition *Anti-foaming 7.0 21.0 34.2 37.8 − 8.3 19.7 34.2 37.8 − ne) to pp g p p g Anti-foaming agents may include but are not limited to dimethicone, silicone oil, simethicone, polydimethylsiloxane, polyethylene glycol, propylene glycol alginate, sorbitan stearate, stearyl alcohol, cetyl alcohol, glyceryl monostearate, magnesium stearate, calcium stearate, stearic acid, triethyl citrate, octadecanol, hydrogenated castor oil, beeswax, carnauba wax, talc. Table 11: The Workable Range of Precipitation Inhibitors (PI) for Manufacturing (i.e.5.0 w / w% or in the shown ranges of below table) PI Types % Mass mposition Table 12a Gel 1 (wet composition) Material name % p Material name % Exemplary Gel 1 and Gel 2 follow a similar manufacturing process, with the main distinction being the use of Soluplus in Gel 1 and Kollidon 12PF in Gel 2. Both gels exhibit similar properties, including slight opacity, and undergo identical steps for mixing, heating, cooking, de-aeration, and filtration. For example, Gel 1 may be prepared by adding Glycerol and (purified) water into a jacketed medicine tank, where the ingredients are mixed at a low speed. Soluplus is then added to the glycerol / water mixture and dissolves within 9 minutes of mixing. As the mixture is gradually heated to 70°C, foam forms and eventually transitions into a white solution. After the dissolution of Soluplus, Gelatin is added, which lowers the temperature of the mixture by approximately 10°C. The mixture is cooked under vacuum at 70°C for 84 minutes to achieve uniform gel formation. After cooking, the gel undergoes final de-aeration under vacuum for 7 minutes to eliminate any air trapped in the gel. The final gel is filtered through a 250-micron filter to remove undissolved particles, and it appears slightly opaque. Special care is taken during the cleaning process to ensure no residue or hard-to-clean white film remains, particularly on the dispersion blade. The exemplary Gel 1 and Gel 2 products, respectively Shell 1 and Shell 2, showed that both had a 20-oblong shape, and acceptable physical attributes in terms of appearance and softgel integrity with hardness of 7.0 N. Capsules with Shell 1 had clear yellow appearance, while capsules Shell 2 were slightly opaque. Burst strength testing revealed no burst capsules in Shell 1 (0 / 20) and 4 / 20 burst capsules in Shell 2, with a burst force of 389 N. Both shells passed the Ph.Eur. disintegration test, with a disintegration time of about 7 minutes.

Claims

CLAIMS What is claimed:

1. A precipitation inhibitor softgel capsule formulation, the formulation comprising: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; and about 10–40% by mass of one or more solvents.

2. The formulation of claim 1, wherein the one or more film-forming polymers comprises gelatin, gelatin hydrolysates, collagen, carrageenans, or agars.

3. The formulation of claim 2, wherein the one or more film-forming polymers comprises gelatin having a Bloom value of about 50 Bloom to about 300 Bloom.

4. The formulation of claim 3, wherein the gelatin has a Bloom value of about 150 Bloom.

5. The formulation of claim 1, wherein the formulation comprises about 20–45% by mass of the one or more film-forming polymers.

6. The formulation of claim 1, wherein the one or more precipitation inhibitors comprise one or more of polyvinylpyrrolidone, polyvinyl acetate phthalate, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co- polymer, poloxamers, polymethylmethacrylates, cellulose acetate phthalate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, derivatives thereof, or combinations thereof.

7. The formulation of claim 1, wherein the formulation comprises about 0.1–10% by mass of the one or more precipitation inhibitors.

8. The formulation of claim 7, wherein the formulation comprises about 1–8% by mass of the one or more precipitation inhibitors.

9. The formulation of claim 7, wherein the formulation comprises about 2.5–5% by mass of the one or more precipitation inhibitors.

10. The formulation of claim 1, wherein the one or more plasticizers or co-solvents comprises solutions of polyols, monosaccharides, disaccharides, oligosaccharides, blended hydrophilic molecules, glycerol, sorbitol, polyethylene glycols, or maltitol.

11. The formulation of claim 1, wherein the formulation comprises about 10–20% by mass of the one or more plasticizers or co-solvents.

12. The formulation of claim 1, wherein the formulation comprises about 0.1-1% by mass of the one or more antifoaming agents.

13. The formulation of claim 1, wherein the one or more neutralization agents comprises NH4OH, NaOH, KOH, or combinations thereof.

14. The formulation of claim 1, wherein the formulation comprises about 0.1–0.5% by mass of the one or more neutralization agents.

15. The formulation of claim 1, wherein the one or more solvents comprises water.

16. The formulation of claim 1, further comprising one or more of colorants, opacifiers, flavors or sweeteners, humectants, preservatives, coatings, viscosity modifiers, fillers or bulking agents, active pharmaceutical ingredients, or buffering salts and acids.

17. The formulation of claim 16, wherein the formulation comprises about 0.01–10% by mass of one or more colorants comprising synthetic dyes, natural dyes, or a combination thereof.

18. The formulation of claim 16, wherein the formulation comprises about 0.01–1% by mass of one or more opacifiers comprising titanium dioxide, zinc oxide, iron oxide, calcium carbonate, or combinations thereof.

19. The formulation of claim 16, wherein the formulation comprises about 0.01–1% by mass of one or more flavors or sweeteners.

20. The formulation of claim 1, wherein the capsule immediately releases at 37 °C at pH 1.2– 7 and delivers the precipitation inhibitor into the medium.

21. The formulation of claim 19, wherein the capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7.

22. A method for manufacturing a precipitation inhibitor softgel capsule, the method comprising: (a) preparing a gel mass composition comprising one or more film-forming polymers, one or more precipitation inhibitors, one or more plasticizers or co-solvents, one or more solvents to form a gel mass, and optionally one or more antifoaming agents; (b) heating the gel mass to create a homogenous and de-aerated gel mass; (c) ageing the homogenous and de-aerated gel mass to create an aged gel mass; (d) casting the aged gel mass into films or ribbons using heat-controlled drums or surfaces; (e) transferring a homogenized fill solution to an encapsulation line; (f) encapsulating the homogenized fill solution within the gel mass films or ribbons using rotary dye encapsulation to create a capsule; (g) drying and finishing the capsule; (h) optionally, printing identification on the capsule; (i) optionally, coating the capsule with a coating and drying; and (j) post processing and packaging.

23. The method of claim 22, wherein the gel mass comprises: about 15–40% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents;about 5–30% by mass of one or more plasticizers or co-solvents; about 10–40% by mass of one or more solvents; and optionally, about 0.1-1% by mass of one or more antifoaming agents.

24. The method of claim 22, wherein heating the gel mass in step (b) comprises a temperature of about 57–80 °C under vacuum for about 15–30 minutes to create the homogenous and de-aerated gel mass.

25. The method of claim 22, wherein ageing the homogenous and de-aerated gel mass in step (c) comprises a temperature of about 50–60 °C for about 12–96 hours to create the aged gel mass.

26. A precipitation inhibitor softgel capsule manufactured by the method of claim 22.

27. A pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes at 37 °C at pH ~1.2–7 and releases the precipitation inhibitor and the one or more B BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250.

28. The pharmaceutical dosage form of claim 27, wherein the precipitation inhibitor softgel capsule comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; about 10–40% by mass of one or more solvents; and optionally, about 0.1-1% by mass of one or more antifoaming agents.

29. A method for administering one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to a subject in need thereof, the method comprising administering to the subject a pharmaceutical dosage form comprising a precipitation inhibitor softgel capsule and a matrix fill comprising the one or more BCS Class II APIs, wherein the precipitation inhibitor softgel capsule dissolves within about 2–10 minutes following administration and releases the precipitation inhibitor and the matrix fill comprising the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250 to the subject, and the precipitation inhibitor inhibits, retards, or prevents precipitation of the one or more BCS Class II or IV active pharmaceutical ingredients (APIs) or APIs having a dose solubility ratio greater than 250.

30. The method of claim 29, wherein the precipitation inhibitor softgel capsule comprises: about 15–45% by mass of one or more film-forming polymers; about 0.01–15% by mass of one or more precipitation inhibitors; about 0.01–1% by mass of one or more neutralizing agents; about 5–30% by mass of one or more plasticizers or co-solvents; about 10–40% by mass of one or more solvents; and optionally, about 0.1-1% by mass of one or more antifoaming agents.

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