Chewable soft gelatin capsule formulation

Abstract

Here is a capsule composition comprising bio-polymers; one or more plasticizers; one or more sugars or sugar alternatives; a sweetener; one or more solvents. The capsule further comprising at least one active pharmaceutical ingredient; bio-polymers; sugars or sugar alternatives; sweeteners; polymeric surface-active agents; and flavoring agents.

Description

[0001] CHEWABLE SOFT GELATIN CAPSULE FORMULATION

[0002] CROSS-REFERENCES TO RELATED APPLICATION(S)

[0003] This application claims the benefit of priority to U.S. Provisional Patent Application No.

[0004] 63 / 776,860, filed March 24, 2025, the disclosures of which are considered part of, and incorporated in their entireties by reference in the disclosure of this application.

[0005] TECHNICAL FIELD

[0006] The present application relates to a formulation of chewable gelatin capsules designed to enhance chewability, taste masking, and patient compliance.

[0007] BACKGROUND

[0008] Gelatin capsules are widely used for oral drug administration due to their ease of swallowing and ability to encapsulate liquid or semisolid formulations. However, conventional gelatin capsules are typically intended to be swallowed whole and may not be suitable for patients with difficulty swallowing pills or capsules. Many active pharmaceutical ingredients (APIs) possess an inherently bitter taste, making palatability a significant challenge.

[0009] To address this, formulations have been developed to provide a more palatable and user-friendly alternative. These capsules should strike a balance between chewability, stability, and effective taste masking. The present invention relates to a chewable gelatin capsule formulated to ensure effective delivery of APIs while optimizing taste and mouthfeel.

[0010] SUMMARY

[0011] This summary introduces concepts further detailed below. It does not define the full scope of the claimed subject matter, and alternative embodiments achieving similar technical effects fall within the scope of the disclosed invention.

[0012] The present invention provides a chewable gelatin capsule formulation wherein the shell and fill matrix (or matrix fill or fill) comprise one or more bio-polymers. These polymers include enzymatically treated or digested gelatin to improve chewability and prevent undesirable crosslinking. The shell composition may further include one or more plasticizers, sugars or sugar alternatives, sweeteners, solvents, and flavoring agents to optimize taste and mouthfeel. The fill matrix may further include additional bio-polymers, polymeric surface-active agents, sweeteners, and complexation agents for taste masking.One aspect is a chewable gelatin capsule formulated comprising one or more biopolymers, wherein said one or more bio-polymers comprise enzymatically treated or digested gelatins. The bio-polymers may be used in either shell composition, fill matrix composition, or both. The capsule is formulated with one or more excipients to enhance chewability and mouthfeel, with the matrix composition solidifying and seamlessly fusing with the shell to create a unified, gummy-like texture.

[0013] Another aspect is a method of manufacturing the chewable gelatin capsule is also provided, comprising: (a) preparation of the shell composition, (b) preparation of the fill matrix, (c) encapsulation using a rotary die process, and (d) optimized drying and post-production processing.

[0014] Another aspect is a matrix composition comprising about 1% to 20% by weight of the matrix composition of at least one active pharmaceutical ingredient; about 5% to about 12% by weight of the matrix composition of bio-polymers; about 30% to about 60% by weight of the matrix composition of sugars or sugar alternatives; about 0.1% to about 5% by weight of the matrix composition of sweeteners; about 1% to about 15%, or up to 15%, by weight of the matrix composition of polymeric surface-active agents; and about less than 2% of flavoring agents.

[0015] Another aspect is a composition of a shell comprising about 20% to about 35% by weight of the wet shell composition of bio-polymers; about 8% to about 35% by weight of the shell composition of one or more plasticizers; about 15% to about 35% by weight of the shell composition of one or more sugars or sugar alternatives; about 0.1% to about 5%, or up to 5%, by weight of the shell composition of a sweetener; and about 10% to about 40% of the shell composition by weight of one or more solvents.

[0016] Another aspect is a composition of shell comprising about 20% to about 35% by weight of the shell composition of bio-polymers; about 8% to about 35% by weight of the shell composition of one or more plasticizers; about 15% to about 35% by weight of the shell composition of one or more sugars or sugar alternatives; about 0.1% to about 5% by weight of the shell composition of a sweetener; and about 10% to about 40% of the shell composition by weight of one or more solvents. Additionally or optionally, the composition comprises a fill matrix, wherein the fill matrix comprises about 1% to 3% by weight of the matrix composition of at least one active pharmaceutical ingredient; about 5% to about 12% by weight of the matrix composition of biopolymers; about 30% to about 60% by weight of the matrix composition of sugars or sugar alternatives; about 0.1% to about 5% by weight of the matrix composition of sweeteners; about 1% to about 15% by weight of the matrix composition of polymeric surface-active agents; and about less than 2% of flavoring agents.DETAILED DESCRIPTION

[0017] Embodiments of the present invention are described below by way of example only. These examples represent a way of putting the invention into practice that are currently known to the applicant although they are not the only ways in which this could be achieved. The description sets forth the functions of the example and the sequence of steps for constructing and operating the example. However, the same or equivalent functions and sequences may be accomplished by different examples.

[0018] Herein described is a chewable gelatin capsule formulation that comprises a shell and a fill matrix that work synergistically to improve the overall sensory experience and effectiveness of the pharmaceutical composition. The shell is composed of bio-polymers, including enzymatically treated or digested gelatin, which provides structural integrity while enhancing chewability. Plasticizers such as glycerol or sorbitol are incorporated to maintain flexibility and prevent brittleness. The inclusion of sugars or sugar alternatives further contributes to texture and sweetness, improving palatability. Additionally, artificial sweeteners and flavoring agents are added to ensure an enjoyable mouthfeel, while solvents facilitate the uniform distribution of ingredients.

[0019] The chewable gelatin capsule as formulated effectively masks the taste of bitter APIs. The integration of polymeric surface-active agents and complexation agents in the fill matrix prevents direct exposure of the Active Pharmaceutical Ingredient (API) to taste receptors, thereby significantly reducing bitterness. The incorporation of enzymatically treated or digested gelatin improves the texture and chewability of the capsule, creating a cohesive, gummy-like consistency that enhances patient compliance. The prevention of gelatin cross-linking further ensures product stability over time, maintaining a consistent mouthfeel and dissolution. It is adapted to enhance the palatability of the formulation. The presence of polymeric surface- active agents may enable the solubilization of poorly water-soluble drugs, it is posited that it could lead to improved absorption and faster onset of action. The inclusion of sugars, polyols, and sweeteners enhances palatability, ensuring a more enjoyable experience for the patient.

[0020] It is further understood that polymeric surface-active agents described herein may act synergistically to form micelles that encapsulate active ingredients. Depending on the hydrophobic or hydrophilic properties of the drug, the drug molecules may be positioned on the micelle surface, within the hydrophilic head groups, or in the outer or inner core of the micelle. Additionally, these non-ionic surfactants can coat the taste receptors, thereby improving the palatability of the chewable soft gelatin capsule.It is appreciated that the present invention represents a significant advancement in oral pharmaceutical dosage forms, providing a patient-friendly alternative to traditional softgel capsules. By combining enhanced taste masking, superior texture, and possibly improved bioavailability, the disclosed formulation optimizes patient compliance and therapeutic efficacy. Variations and modifications in formulation components, processing methods, and excipient selection are within the scope of the invention, as would be recognized by one skilled in the art.

[0021] Various ranges disclosed herein are understood to include both end 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. The term “etc.” refers to a combination of any of the specific percentages and ranges, as well as any other intermediate values and subranges within the broader range of the total wet mass of the shell. This includes all conceivable fractions and decimals and so forth.

[0022] The manufacturing process for the chewable soft gelatin capsule requires optimization to ensure product consistency, effective taste masking, and overall process efficiency. Excessive foaming during manufacturing can complicate handling, however, disrupt processing conditions, and compromise formulation uniformity. Modifications were made to the formulation, as described herein, to minimize foaming while preserving the desired product characteristics. The formulation may include one or more polymeric surface-active agents in one or more concentrations described herein. For example, the polymeric surface-active agents may comprise one or more of polyoxyl 40 hydrogenated castor oil (Kolliphor RH40), poloxamer 188, 124, 237, 407 (Kolliphor P 188), and polyvinylpyrrolidones, as kolliphors or kolliphor compounds, whereby kolliphor compounds refer to compounds chemically like Kolliphor or Kolliphor RH40. Kolliphor compounds may also be a group of nonionic surfactants that are generic equivalents of generic equivalents that function in the formulation as solubilizers, emulsifiers, solubilizers, dispersing agents, and / or stabilizers.

[0023] Moreover, the gelatin shell formation showed instances where fill-surface interactions led to a "ghosting" effect, where the fill and shell appeared to separate. This issue was observed in early tasting trials and was attributed to inconsistencies in gelatin hydration and fill viscosity. Modifications, such as refining the excipient ratios (i.e., plasticizer-to-gelatin ratio) with respect to other excipients (i.e., bio-polymers), helped to improve cohesion between the shell and fill, ensuring a more uniform texture and chewability.When Dextromethorphan is used as the API, it is shown experimentally to have significant improvements in these aspects, particularly improved capsule formulation successfully overcoming key challenges related to bitterness, texture, and manufacturing efficiency, leading to an improved consumer-acceptable product. For example, formulations containing 30 mg of Dextromethorphan HBr exhibited excessive bitterness and an unpleasant numbing effect. By reducing the API content to 15 mg per capsule and increasing the fill weight from 747 mg to 1000 mg in relation to the fill formation described herein, the capsule achieved a more acceptable taste profile. Additionally, the incorporation of polymeric surface-active agents effectively delayed the perception of bitterness, improving the overall sensory experience.

[0024] Experimentation also revealed hard-to-chew textures and a "ghosting" effect, where the shell and fill separated upon mastication. To address this, the excipient ratio was refined, enhancing cohesion between the shell and fill. Incorporating an enzymatically treated gelatin grade developed to mitigate crosslinking, along with adapting the gelatin content in the shell, enhanced chewability and eliminated the ghosting effect observed in various trials. Stability studies confirmed that the optimized formulation maintains API content within specification, with minimal loss due to process adjustments. Taste panel evaluations indicated that the final chewable formulation was rated as “pleasant” or “slightly bitter” with a fresh taste, marking a significant improvement compared to traditional capsules containing the same API.

[0025] As used herein, film-forming polymers refer to polymers capable of forming a continuous, cohesive, and stable film when applied in solution or dispersion form and subjected to drying or curing. Film-forming polymers may exhibit flexibility, adhesion, and mechanical strength, making them suitable for pharmaceutical, nutraceutical, and edible applications. Film-forming polymers may be used as protective coatings, encapsulating matrices, or structural shells, such as those used in gelatin capsules. Film-forming polymers may include both natural and synthetic polymers, which may be modified or unmodified, and are selected based on their compatibility with the API, flavoring agents, and other excipients. It is understood that some film-forming polymers may be bio-polymers.

[0026] One aspect of film-forming polymers may be used together with one or more bio-polymers such that some bio-polymers may include film-forming characteristics; a bio-polymer herein refers to a polymer with biological properties or produced biologically, such as an enzymatically modified gelatin. These polymers may comprise gelatin that has been chemically, enzymatically, or physically altered to modify its properties for specific applications. For example, a bio-polymer may comprise a water-soluble polymer agent capable of forming a film that enhances the integrity of a shell or shell capsule, i.e. , modified gelatin, or enzymatically treated or digested gelatin, whichenhances the chewability, flexibility, and stability of the shell, whereas film-forming polymers may also comprise gelatin, hydroxypropyl methylcellulose (HPMC), or Polyvinylpyrrolidone (PVP) may be used in addition to or in combination with modified gelatin to provide structural integrity and control the release of the API. In one aspect, one or more bio-polymers may comprise modified gelatin, enzymatically treated gelatin, digested gelatin, or a combination thereof.

[0027] In some embodiments, bio-polymers may comprise a mass percentage of about 20%-35% of the total wet mass of a shell, including each integer and fraction within the specified range. For example, one or more bio-polymers may comprise a mass percentage of about 20%, 25%, 30%, 35%, or about 20-25%, 20-30%, or 20-35% 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 bio-polymers may comprise a mass percentage of about 5%-12% of the total wet mass of a fill matrix, including each integer and fraction within the specified range.

[0028] Publications have discussed the use of enzymatically treated or digested gelatin, though not applicable in chewable technology. For example, a special blend of enzymatically treated or digested gelatin, used as a raw material (e.g., Gelatin Stabicaps™, sourced from gelatin manufacturer Rousselot), is substantially described in EP 3,487,486 B1, US 7,485,323 B2, and US 7,897,728 B2, which are hereby incorporated by reference in their entirety. It is appreciated that various types of enzymatically treated or digested gelatin may be used, either as a substitute for Gelatin Stabicaps™ or in combination with it. Further examples of the special blend of enzymatically treated / digested gelatin are described herein.

[0029] Plasticizers refer to substances added to polymer compositions to enhance flexibility, reduce brittleness, and improve the mechanical properties of the resulting film or structure, which are useful for forming durable, flexible, and chewable gelatin capsules, as well as for preventing cracking or breaking during processing and use. Plasticizers function by reducing the intermolecular forces within the polymer, thereby increasing polymer chain mobility.

[0030] Examples of a plasticizer may be an agent that adds extensibility, dispensability, flexibility, elasticity, rigidity, pliability, and / or enhanced mechanical properties to a shell by interacting with the bio-polymer. The plasticizer can minimize the brittleness and cracking of the shell. In fact, the mixtures of two or more plasticizers may be used to optimize the mechanical and organoleptic properties of the shell or matrix.

[0031] Plasticizers may be selected based on their compatibility with the bio-polymers, APIs, and other excipients used in the shell or matrix composition. Plasticizers may comprise glycerol or sorbitol, which provides optimal flexibility and stability to the gelatin shell. Plasticizers may also include one or more polyhydric alcohols such as glycerol (glycerin) sorbitol, mannitol, maltitol,xylitol, or a combination thereof. Plasticizers may be used to enhance chewability and improve the mouthfeel of the capsule.

[0032] One aspect of plasticizer may comprise glycerol (glycerin) sorbitol, mannitol, maltitol, xylitol, or a combination thereof, or a derivative thereof. Plasticizers may comprise a mass percentage of about 8%-35% of the total wet mass of a shell, including each integer and fraction within the specified range. For example, one or more plasticizers may comprise a mass percentage of about 8%, 10%, 12%, 15%, 18%, 20%, 22%, 25%, 28%, 30%, 35%, or 8-10%, 8-12%, 8-15%, 8-18%, 8-20%, 8-22%, 8-25%, 8-28%, 8-30%, 8-35%, etc. of the total wet mass of a shell, including each integer and fraction within these specified values and ranges. It is understood that the weight ratio between the bio-polymer, plasticizer, and solvent is adjusted so that the gel mass is flowable and not too viscous and can be made into capsules using rotary die encapsulation methods.

[0033] Sugar or sugar alternative refers to compounds that provide sweetness, contribute to the structural integrity of compositions, and enhance the organoleptic properties (taste, texture, and mouthfeel) of the product. These compounds may include mono-, di-, or polysaccharides, as well as non-caloric or low-caloric compounds, either in natural or synthetic forms. Sugars and sugar alternatives are critical in the shell and matrix compositions of chewable gelatin capsules to mask bitterness, improve palatability, and support the chewable texture. Sugars and sugar alternatives may be selected based on their compatibility with other components, their stability during processing, and their ability to mask unpleasant flavors of APIs. The sugars or sugar alternatives in suitable amounts may be used to achieve the desired sweetness, stability, and organoleptic properties. The sugar or sugar alternative used may comprise glucose, sucrose, polysaccharides, glucose liquid, sucralose, or a combination thereof. For example, a combination of sucrose and glucose liquid may be used with polymeric surface-active agents for masking or reducing the bitterness of the API while contributing to the chewable texture and mouthfeel.

[0034] One aspect of sugar or sugar alternatives may comprise glucose, sucrose, polysaccharides, glucose liquid, sucralose, or a combination thereof. Sugar or sugar alternatives may comprise a mass percentage of about 15%-35% of the total wet mass of a shell, including each integer and fraction within the specified range. For example, one or more plasticizers may comprise a mass percentage of about 15%, 18%, 20%, 22%, 25%, 28%, 30%, or 35% or 15-18%, 15-20%, 15-20%, 15-22%, 15-28%, 15-30%, 15-35%, etc., of the total wet mass of a shell, including each integer and fraction within these specified values and ranges.

[0035] Solvents refer to compounds that act as carriers or diluents to dissolve, disperse, or mix the components of the shell or matrix compositions. Solvents are essential for forminghomogenous solutions or dispersions of bio-polymers, plasticizers, APIs, and other excipients during the preparation process. In the final product, solvents may remain in trace amounts or may be partially or completely evaporated during drying or curing. Solvents may be selected based on their compatibility with the other components, safety profile, and processing requirements. For example, the solvent may comprise aqueous solvents such as purified water, semi-aqueous solvents organic solvents, or a combination thereof.

[0036] For example, a solvent may be an aqueous agent used to solubilize the various components of a shell formulation. In some embodiments, the solvent comprises about 10%-40% by mass of the shell, including all integers and fractions within the specified range. In one embodiment, the solvent is water (e.g., purified water). The quantity of water in the composition varies depending on the quantities of the other ingredients. 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%. In another embodiment, the water comprises about 15 to 35% by weight, about 15%, about 20% about 25%, about 30%, about 35% by mass of the shell formulation. In another embodiment, water comprises about 20%-36%. In one embodiment, water comprises about 35% by mass of the composition.

[0037] Flavoring agents refer to compounds or mixtures added to improve the taste and organoleptic properties of the product. The flavoring agents may comprise one or more essential oils such as peppermint oil, spearmint oil, and citrus oil to enhance taste and mask some bitterness of API percentage. In another embodiment, flavoring agent comprises about 2% by weight, or up to or less than 2% by mass of the shell formulation. In one embodiment, flavoring agent comprises about 1% or less than 1% by mass of the composition.

[0038] Colorants refer to substances added to impart or enhance the visual appeal of the product. Colorants may comprise one or more of FD&C Blue #1 (E133), FD&C Red #40 (E129), FD&C Yellow #5 (E102), FD&C Green #3 (E143), curcumin, anthocyanins, and chlorophyll to provide a visually appealing color, with the option to include titanium dioxide for additional opacity. In one embodiment, colorant comprises about 1%, less than 1%, or 0% by mass of the composition.

[0039] Colorants may be used for marketing and product identification / differentiation purposes. Suitable colorants include synthetic and natural dyes and combinations thereof. When included in shell composition, as described herein, colorants typically comprise a mass percentage of about 0-10% of the total wet mass of a shell, including each integer and fraction within this specified range. In some embodiments, one or more colorants may comprise a mass percentage of about 0%, 0.01%, 0.1%, 0.25%, 0.5%, 1%, 2%, 2.5%, 5%, 7.5%, or 10%, 0-0.01%, 0-0.1%, 0-0.5%, etc., 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 0-1% of the total wet mass of a shell, including each integer and fraction within this specified range.

[0040] Polymeric surface-active agents refer to high-molecular-weight compounds that possess both hydrophilic and hydrophobic regions, enabling them to reduce surface tension, stabilize emulsions, and enhance solubility or dispersion of hydrophobic components in aqueous systems. Polymeric surface-active agents may comprise one or more non-ionic surfactants that is used in amount described herein to taste mask, emulsify the APIs, and might improve the bioavailability of poorly water-soluble drugs. Polymeric surface-active agents may comprise non-ionic surfactants such as polyoxyl 40 hydrogenated castor oil, and poloxamer 188, 124, 237, 407. The polymeric surface-active agents may further comprise high molecular weight hydrophilic polymers like polyethylene oxides. Cyclodextrins may also be used as complexation agents. Amphiphilic polymers such as polyvinyl alcohol (PVA) and polyethylene glycol (PEG)-based surfactants may sometimes be used. Other examples of polymeric surface-active agents may also include block copolymers, such as Pluronics (e.g., F68 and F127), and natural emulsifiers like lecithin. The polymeric surface-active agents described herein act synergistically to enhance the solubility of hydrophobic active ingredients like Loratadine. Kolliphors described herein, i.e., polyoxyl 40 hydrogenated castor oil, provide effective emulsification and solubilization, while poloxamer 188 offers additional stabilization of the emulsion, contributing to uniform dispersion and taste masking. Together, these agents improve the palatability and bioavailability of the active ingredient, ensuring consistent therapeutic efficacy of the chewable gelatin capsule as herein described. In some embodiments, polymeric surface-active agents may comprise a mass percentage of about 0%, 1%, 2%, 5%, 7%, 10%, 12%, 15%, 0-1%, 0-2%, 0-5%, etc., of the total wet mass of a shell, including each integer and fraction within these specified values and ranges. In some embodiments, polymeric surface-active agents may comprise a mass percentage of about 0-15% of the total wet mass of a fill matrix, including each integer and fraction within this specified range. In one embodiment, a polymeric surface-active agent may comprise a mass percentage of about 12% of the total wet mass of a fill matrix.

[0041] Complexation agents refer to compounds capable of forming molecular complexes with other substances, i.e., APIs in the chewable gelatin capsule, to alter their physical, chemical, or sensory properties. These agents interact with APIs through non-covalent bonds, such as hydrogen bonding, van der Waals forces, or ionic interactions, to reduce bitterness, improve solubility, enhance stability, or control its release profile. Complexation agents may comprisebeta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, polyethylene oxides, which effectively encapsulate API such as Dextromethorphan Hydrobromide to reduce its bitterness and increase solubility. Complexation agents may be used alone or in combination with polymeric surfaceactive agents using one or more kolliphors, providing synergistic effects for taste masking and uniform dispersion. In some embodiments, complexation agents may comprise a mass percentage of about 0%, 1%, 2%, 5%, 7%, 10%, 12%, 15%, 0-1%, 0-2%, 0-5%, etc., of the total wet mass of a fill, including each integer and fraction within these specified values and ranges. In some embodiments, complexation agents may comprise a mass percentage of about 0-15% of the total wet mass of a fill, including each integer and fraction within this specified range. In one embodiment, a complexation agent may comprise a mass percentage of about 15% of the total mass of a fill.

[0042] Polymer modifiers refer to compounds added to enhance or alter the physical, chemical, or mechanical properties of bio-polymers in the shell or matrix compositions. Polymer modifiers improve processability, stability, and performance by adjusting parameters such as viscosity, elasticity, solubility, pH, or compatibility with other excipients. Polymer modifiers are particularly useful in optimizing the chewability, flexibility, and taste-masking characteristics of chewable gelatin capsules. The use of polymer modifiers is particularly advantageous in the present invention as it allows for fine-tuning of the mechanical and sensory properties of the capsule. Polymer modifiers may comprise lactic acid, fumaric acid, citric acid, tartaric acid, or a combination thereof. Their inclusion enables the formulation of a chewable capsule with improved patient compliance and consistent therapeutic efficacy. In one embodiment, polymer modifier comprises about 1%, less than 1%, or 0% by mass of the composition.

[0043] Sweeteners refer to compounds that provide sweetness to the formulation without significantly contributing to caloric content or glycemic impact. For example, sweeteners may comprise sucralose, acesulfame potassium, or a combination thereof. Less sugar or sugar alternatives, sweeteners function to enhance the organoleptic properties of the chewable gelatin capsule and improve the overall taste.

[0044] In one embodiment, the matrix fill comprises one or more sweeteners. In another embodiment, the shell composition comprises one or more sweeteners. In another embodiment, the matrix fill and the shell composition comprise 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®, Truvia®), saccharin, calcium saccharin, sodium saccharin, aspartame, Neotame®, acesulfame potassium, agave nectar, high-fructose corn syrup, honey, dextrates, dextrose, excipient dextrose and simple sugars such asglucose, fructose, sucrose, 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 (e,g MagnaSweet®), or combinations thereof. In some embodiments, sweeteners may comprise a mass percentage of about 0%, 0.1%, 0.5%, 1%, 2%, 5%, 7%, 10%, 12%, 15%, 0-0.1%, 0-0.5%, 0-1%, etc., of the total wet mass of a shell and / or fill composition, including each integer and fraction within these specified values and ranges. In some embodiments, sweeteners may comprise a mass percentage of about 0.1-5% or up to 5% of the total wet mass of a shell and / or fill composition, including each integer and fraction within this specified range. In one embodiment, sweeteners may comprise a mass percentage of about 0.2% of the total wet mass of a shell.

[0045] 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 terms “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.

[0046] 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.”

[0047] The term “active ingredient” or “active pharmaceutical ingredient” or “active pharmaceutical agent” or “API” or “drug” as used herein 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 activeingredient and any of its pharmaceutically acceptable salts or esters. In some embodiments, one or more APIs may be incorporated into a matrix fill as described herein. In some embodiments, one or more APIs may be incorporated into a pressed tablet as described herein. In some embodiments, one or more APIs may be incorporated into a formulation as described herein.

[0048] 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 capsules.

[0049] 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 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.

[0050] The term “formulation” or “composition” refers to the API 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.

[0051] The term “room temperature” refers to common ambient temperatures found in pharmaceutical laboratories ranging from about 20 °C to about 27 °C.

[0052] The term “weight percent,” “% wt,” “mass percent,” or “percent mass” refers 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 term “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.

[0053] The term “wet shell mass,” or “wet capsule mass” refers to the mass of the capsule during formulation and manufacturing but before drying. During the manufacturing process, 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-fugitive components increase 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.Other suitable shell additives include plasticizers, opacifiers, colorants, humectants, preservatives, viscosity modifiers, flavorings, and buffering salts and acids. Further suitable shell additives may also include viscosity modifying polymers. Unlike viscosity modifiers, the viscosity modifying polymers act as viscosity reducing agents rather than binding agents. The viscosity modifying polymers decrease the viscosity of the gel formulation while maintaining similar shell stability, and without affecting the shell rupture time and disintegration time.

[0054] In some embodiments, the capsule described herein includes one or more taste suppressors. In certain formulations, sodium salts such as sodium acetate, sodium chloride, and sodium saccharin may be incorporated at concentrations of about 0.5% to 3%. The formulation has been observed to reduce bitterness and enhance the overall taste profile.

[0055] Said one or more taste suppressors are believed to exert their effects through multiple mechanisms. One proposed mechanism is that sodium interacts with G-protein coupled receptors (GPCRs) by forming an ionic shield around specific protein regions, thereby reducing the receptor’s affinity for bitter compounds or altering protein folding to achieve a similar effect.

[0056] Studies have shown that sodium may also influence ion channels involved in taste transduction, further contributing to bitterness suppression. For example, taste suppressors such as sodium salts, when incorporated into a formulation, not only enhance salt perception but also modulate flavor by suppressing undesirable tastes, such as bitterness, while enhancing desirable ones, such as sweetness, in combination with one or more excipients, as part of said formulation described herein.

[0057] It is understood that various range or ranges described herein are tested and selected to optimize the chewability, stability, and overall effect of the chewable soft gelatin capsule. These ranges ensure a balance between mechanical integrity and flexibility, preventing brittleness while maintaining a pleasant texture. For example, selected ranges of bio-polymers may contribute to the formation of a cohesive shell that, in conjunction with one or more other excipients, maintains its structure while enhancing chewability. In another example, the inclusion of plasticizers within specified ranges prevents excessive hardness or stickiness, ensuring a smooth mouthfeel.

[0058] Shell Compositions

[0059] The shell composition comprises one or more bio-polymers, including enzymatically treated or digested gelatin, which enhances the chewability of the capsule and prevents undesirable cross-linking. The inclusion of plasticizers, such as glycerol and sorbitol, ensures flexibility, preventing brittleness and improving the mouthfeel of the shell. To further enhance thesensory experience, the shell incorporates sugars or sugar alternatives, such as maltitol or glucose syrup, contributing to sweetness while maintaining the required consistency.

[0060] Shell may further comprise artificial sweeteners and flavoring agents, such as sucralose, acesulfame potassium, and natural fruit flavors, which help mask any residual bitterness of the API. Solvents, primarily purified water, are utilized to facilitate the homogeneous dispersion of the ingredients during the manufacturing process, ensuring an even texture and optimal processing characteristics. In some embodiments, colorants and opacifiers may also be added to provide an aesthetically pleasing appearance and improve patient compliance.

[0061] It is understood that the shell composition is balanced to ensure a seamless fusion with the fill matrix, allowing for a cohesive, gummy-like consistency upon mastication. The weight ratio of the bio-polymer, plasticizer, and solvent is optimized to maintain proper gel mass flow properties suitable for rotary die encapsulation. By integrating these excipients, the chewable gelatin shell effectively encapsulates the fill while providing a pleasant sensory experience and ensuring the stability of the API.

[0062] It is further understood that chewable soft capsule shells are described in US8097279 BB, US8241665 BB, US8765174 BB, US8414916 BB, US9072677 BB, US9668976 BB, US9861586 BB, US10342763 BB, EP1496873 B1, CN102600104 B, DE60319355 D1, ES2302926 T3, ES2302926 T5, IN240622 B, JP4995407 B2, each of which is in incorporated by reference herein for such teachings.

[0063] Fill Compositions

[0064] The fill (matrix) comprises bio-polymers, such as modified gelatin or HPMC, which contribute to the cohesive structure of the matrix while allowing for controlled release of the API. The incorporation of polymeric surface-active agents, i.e., kolliphors, facilitates the solubilization and dispersion of hydrophobic APIs, enhancing their bioavailability and therapeutic efficacy. It is appreciated that polymeric surface-active agents may also be used as coating agents for the API. This is due to the nature of polymeric surface-active agents being able to mask the burning sensation of certain bitter tastes (i.e., from Zinc in mouthwash). The preparation of polymeric surface-active agents, i.e., Kolliphor RH 40, which are hereby incorporated by reference in their entirety.

[0065] The fill composition may further comprise complexation agents, such as cyclodextrins and polyethylene oxides, which interact with the API to minimize its exposure to taste receptors. Additionally, sweeteners, including sorbitol, maltitol, and sucralose, are included to enhancepalatability and contribute to the overall sensory profile. Plasticizers, such as propylene glycol or glycerol, are added to modify viscosity and ensure smooth consistency.

[0066] The fill composition may further comprise solvents, primarily purified water, to maintain homogeneity during manufacturing and prevent phase separation. In some embodiments, buffering agents and polymer modifiers, such as citric acid or tartaric acid, may be incorporated to regulate pH and optimize stability. The fill matrix is designed to be homogeneous and stable, ensuring uniform API distribution within each capsule while providing a pleasant mouthfeel and effective drug delivery.

[0067] One aspect is a matrix composition comprising about 1% to 20%, up to 20%, or up to 25% by weight of the matrix composition of at least one active pharmaceutical ingredient; about 5% to about 12% by weight of the matrix composition of bio-polymers; about 30% to about 60% by weight of the matrix composition of sugars or sugar alternatives; about 0.1% to about 5% by weight of the matrix composition of sweeteners; about 1% to about 15% by weight of the matrix composition of polymeric surface-active agents; and about less than 2% of flavoring agents.

[0068] Another aspect is a composition of a shell comprising about 20% to about 35% by weight of the shell composition of bio-polymers; about 8% to about 35% by weight of the shell composition of one or more plasticizers; about 15% to about 35% by weight of the shell composition of one or more sugars or sugar alternatives; about 0.1% to about 5% by weight of the shell composition of a sweetener; and about 10% to about 40% of the shell composition by weight of one or more solvents.

[0069] Another aspect is a composition of shell comprising about 20% to about 35% by weight of the shell composition of bio-polymers; about 8% to about 35% by weight of the shell composition of one or more plasticizers; about 15% to about 35% by weight of the shell composition of one or more sugars or sugar alternatives; about 0.1% to about 5% by weight of the shell composition of a sweetener; and about 10% to about 40% of the shell composition by weight of one or more solvents. Additionally or optionally, the composition comprising a fill matrix, wherein the fill matrix comprising about 1% to 3% by weight of the matrix composition of at least one active pharmaceutical ingredient; about 5% to about 12% by weight of the matrix composition of biopolymers; about 30% to about 60% by weight of the matrix composition of sugars or sugar alternatives; about 0.1% to about 5% by weight of the matrix composition of sweeteners; about 1% to about 15% by weight of the matrix composition of polymeric surface-active agents; and about less than 2% of flavoring agents.

[0070] Another aspect or option is about 1% or less than 1% by weight of flavoring agents and colorants. Another aspect or option is polymeric surface-active agents comprising one or morenon-ionic surfactants. Another aspect or option is said one or more non-ionic surfactants comprise a combination of one or more kolliphors. Another aspect or option is the polymeric surface-active agents comprise one or more complexation agents. Another aspect or option is said one or more complexation agents comprise up to about 15% of cyclodextrins. Another aspect or option is the polymeric surface-active agents comprise one or more high molecular weight polymers. Another aspect or option is said one or high molecular weight polymers comprise up to about 15% of polyethylene oxides. Another aspect or option is the matrix composition further comprising about 1% by weight of the matrix composition of polymer modifiers of lactic acid, fumaric acid, citric acid, tartaric acid, or a combination thereof. Another aspect or option is said at least one active pharmaceutical ingredient comprises dextromethorphan hydrobromide at about 1.5% by weight of the matrix composition. Another aspect or option is said at least one active pharmaceutical ingredient comprises paracetamol at about 15% by weight of the matrix composition.

[0071] Another aspect or option is the shell composition comprising about 30% by weight of the shell composition of a bio-polymer; about 21% by weight of the shell composition of a plasticizer; about 24% by weight of the shell composition of a sugar; about 0.2% by weight of a sweetener; and about 24% of the shell composition by weight of water.

[0072] Another aspect or option is the matrix composition comprising: about 2% by weight of the matrix composition of at least one active pharmaceutical ingredient; about 7% by weight of the matrix composition of a bio-polymer; about 24% by weight of the matrix composition of glucose; about 24% by weight of the matrix composition of sucrose; about 2.5% by weight of the matrix composition of sweeteners; about 12% by weight of the matrix composition of polymeric surfaceactive agents; about less than 1% of the matrix composition of a flavoring agent; about less than 1% of the matrix composition of a polymer modifier; and about 30% of the matrix composition of a solvent.

[0073] Another aspect or option is the bio-polymers comprise one or more modified gelatin polymers. Another aspect or option is said one or more modified gelatin polymers comprise enzymatically treated gelatin, digested gelatin, or a combination thereof. Another aspect or option is said one or more plasticizers comprise glycerol, sorbitol, mannitol, maltitol, xylitol, or a combination thereof. Another aspect or option is said one or more sugar or sugar alternatives comprise glucose, sucrose, polysaccharides, glucose liquid, sucralose, ora combination thereof. Another aspect or option is said one or more sweeteners comprise sucralose, acesulfame potassium, or a combination thereof. Another aspect or option is said one or more solvents comprise purified water.Another aspect or option is a method of manufacturing the chewable soft gelatin capsule comprising the steps of: preparing a shell composition by heating and homogenizing one or more bio-polymers, plasticizers, sugars, sugar alternatives, and sweeteners, optionally incorporating one or more flavoring agents and colorants; preparing a matrix composition by incorporating at least one active pharmaceutical ingredient with one or more sugars, sugar alternatives, sweeteners, polymeric surface-active agents, and flavoring agents to form a homogeneous mixture; encapsulating the homogeneous mixture within the shell composition through a rotary die process; drying the encapsulated homogeneous mixture to form the chewable soft gelatin. Another aspect or option comprising conducting one or more post-production activities on the chewable soft gelatin to achieve desired physical and organoleptic attributes.

[0074] Some embodiments are shell composition and fill matrix composition of the chewable soft gelatin capsule. In one embodiment, the shell comprises about 30% by weight of a bio-polymer, specifically a special blend of enzymatically treated or digested gelatin, which improves chewability and prevents crosslinking. The shell may further comprise about 21% by weight of plasticizers selected from glycerol, sorbitol, mannitol, maltitol, or xylitol, providing optimal elasticity and softness. Additionally, about 24% by weight of sugars, such as glucose and sucrose, contribute to sweetness and mouthfeel. Sweetness is further enhanced by the inclusion of about 0.2% by weight of artificial sweeteners, such as sucralose or acesulfame potassium, and about 24% by weight of purified water serves as a solvent. Flavoring agents and colorants may be included at about 1% or less by weight to improve taste and appearance.

[0075] In another embodiment, the fill matrix comprises about 7% by weight of the same special blend of enzymatically treated or digested gelatin as the matrix-forming polymer, ensuring structural cohesion. The matrix also includes about 2% by weight of the active pharmaceutical ingredient, preferably dextromethorphan hydrobromide, for therapeutic effectiveness. Sugars and sugar alternatives, such as glucose and sucrose, are present at about 24% by weight each, providing sweetness and chewability. Artificial sweeteners, including sucralose and acesulfame potassium, are included at about 2.5% by weight for additional taste masking. To further suppress the bitterness of the active ingredient, about 12% by weight of polymeric surface-active agents, specifically a combination one or more kolliphors, are used. Optional polymer modifiers such as citric acid or tartaric acid may be added at less than 1% by weight to optimize pH and stability. The solvent, primarily purified water, makes up about 30% by weight of the fill matrix, ensuring homogeneity and proper dispersion of ingredients.

[0076] In another embodiment, the chewable soft gelatin capsule comprises enzymatically treated or digested gelatin to ensure seamless fusion between layers of the shell and fill matrix.The inclusion of polymeric surface-active agents, such as polyoxyl 40 hydrogenated castor oil and poloxamer 188, within the fill matrix effectively encapsulates and disperses the bitter active ingredient, while the combination of sugars, polyols, sweeteners, and flavoring agents in both the shell and fill matrix improves taste and mouthfeel.

[0077] APIs

[0078] The chewable soft gelatin capsule formulation described herein is suitable for delivering a wide range of APIs, including but not limited to antitussives, analgesics, antihistamines, decongestants, vitamins, and other therapeutic agents. This formulation may be advantageous for APIs that exhibit poor palatability, low water solubility, or require enhanced bioavailability. The inclusion of polymeric surface-active agents and complexation agents within the fill matrix allows for improved solubilization of hydrophobic APIs, facilitating more efficient absorption in the gastrointestinal tract. APIs prone to degradation in aqueous environments benefit from encapsulation within the soft gelatin shell, providing protection from moisture and ensuring stability over time.

[0079] For taste-sensitive APIs, such as dextromethorphan hydrobromide, diphenhydramine hydrochloride, loratadine, chlorpheniramine maleate, and phenylephrine hydrochloride, the formulation employs multiple taste-masking strategies. Other APIs may include compounds with antipyretic and analgesic such as acetaminophen or paracetamol. These may include the use of polymeric coatings, complexation with cyclodextrins, and the incorporation of sweeteners and flavoring agents. These components work synergistically to reduce the perception of bitterness, making the dosage form more palatable for patients, particularly pediatric and geriatric populations. Furthermore, the chewable nature of the soft gelatin capsule allows for a controlled release of the API upon mastication.

[0080] The percentage of API in the fill matrix may be in the range of about 1%-5% by weight, depending on the potency and therapeutic dose of the active ingredient. For example, dextromethorphan hydrobromide may be present at about 1.5%-3% by weight, diphenhydramine hydrochloride at about 2%-4% by weight, and phenylephrine hydrochloride at about 1%-2.5% by weight. These concentrations are optimized to achieve the desired pharmacokinetic profile while maintaining a pleasant taste and chewable texture. In some embodiments, APIs may comprise a mass percentage of about 1%, 1.1%, 1.2%, 1.3%, etc., and 1%-1.1%, 1%-1.2%, 1%-1.3%, etc., of the total wet mass of a shell, including each integer and fraction within these specified values and ranges. In some embodiments, APIs may comprise a mass percentage of about 1%-5% of the total wet mass of a shell, including each integer and fraction within this specified range. In oneembodiment, API may comprise a mass percentage of about 1.5% and up to 20% of the total wet mass of a shell with the fill composition.

[0081] The formulation is adaptable to immediate-release, modified-release, or sustained-release APIs, depending on the selection of excipients and processing conditions. APIs with a rapid onset of action, such as dextromethorphan hydrobromide for cough suppression or phenylephrine hydrochloride for nasal decongestion, may be formulated for immediate dissolution in saliva and subsequent absorption in the stomach or small intestine. Sustained-release formulations can be designed to extend therapeutic effects over time, such as with loratadine for long-lasting antihistamine relief. The flexibility in API incorporation, combined with the improved patient compliance associated with chewable dosage forms, makes this formulation an effective alternative to traditional tablets, capsules, and liquid suspensions.

[0082] Manufacturing and Administration

[0083] The manufacturing process of chewable soft gelatin capsules may begin with preparing the either shell, the matrix fill, or both simultaneously. The shell may be prepared by heating and homogenizing bio-polymers, plasticizers, sugars, and sweeteners, with optional flavoring agents and colorants. Matrix fill may be prepared by blending the active pharmaceutical ingredient with sugars, sweeteners, surfactants, and flavoring agents to ensure uniform dispersion, stability, and bioavailability. The homogeneous fill is then encapsulated within the shell using a rotary die process, followed by controlled drying to maintain consistency and shape. Finally, or as an option step, the dried capsules undergo quality control checks before packaging, with optional postproduction refinements to enhance physical and sensory properties.

[0084] The process may follow the steps of: preparing a shell composition by heating and homogenizing one or more bio-polymers, plasticizers, sugars, sugar alternatives, and sweeteners, optionally incorporating one or more flavoring agents and colorants; preparing a matrix composition by incorporating at least one active pharmaceutical ingredient with one or more sugars, sugar alternatives, sweeteners, polymeric surface-active agents, and flavoring agents to form a homogeneous mixture; encapsulating the homogeneous mixture within the shell composition through a rotary die process; drying the encapsulated homogeneous mixture to form the chewable soft gelatin; and optionally conducting one or more post-production activities on the chewable soft gelatin to achieve desired physical and organoleptic attributes.

[0085] One aspect of the process may begin with the preparation of the shell composition, where bio-polymers, plasticizers, sugars, sugar alternatives, and sweeteners are heated and homogenized. Flavoring agents and colorants may also be incorporated. Subsequently, the matrixcomposition is prepared by blending at least one active pharmaceutical ingredient with sugars, sugar alternatives, sweeteners, polymeric surface-active agents, and flavoring agents to form a homogeneous mixture. The homogeneous matrix can be encapsulated within the shell composition using a rotary die process, ensuring proper formation and integrity. The encapsulated product then undergoes a drying phase under controlled conditions to achieve the desired consistency and stability.

[0086] Based on trial observations, process improvements such as pre-melting surfactants to reduce mixing time, increasing gelatin content to enhance fill-shell fusion, and optimizing vacuum deaeration cycles to minimize foaming have been recommended. These refinements ensure batch-to-batch consistency, effective taste masking, and enhanced patient acceptability in the final capsule product.

[0087] The manufactured capsule may be administered orally. The capsules are to be chewed thoroughly before swallowing, allowing for effective taste masking and enhanced palatability. The dosage regimen can be tailored based on the therapeutic indication, with administration occurring once (QD), twice (BID), three times (TID), or four times daily (QID), or as needed, depending on the prescribed treatment. The formulation is designed for both short-term and long-term use with a shelf life of at least 2 years or upto 2 years, with treatment durations ranging from a single dose to several weeks or months as required. The chewable capsules can be taken with or without food, depending on the pharmacokinetic properties of the API. For APIs that require fasting conditions for optimal bioavailability, administration on an empty stomach may be preferred. Multiple doses may be taken simultaneously, when necessary, either in identical or varying strengths, to achieve the desired therapeutic effect. The versatility of this dosage form enhances patient adherence and convenience while ensuring effective drug delivery.

[0088] EXAMPLES

[0089] Example 1

[0090] Fill Matrix Formulation _

[0091] _ Component _ Function _ w / w (%)

[0092] Sugar Glucose liquid 23.62

[0093] Sucrose granular 23.75

[0094] Sweetener Sucralose 1.00

[0095] Acesulfame k 1.50

[0096] Polymer modifier Citric acid, anhydrous 0.37

[0097] Solvent Water 29.45Kolliphor RH40 (Polyoxyl 3.00 Polymeric Surface-active 40 castor oil))

[0098] agents Kolliphor P 188 8.00

[0099] (Poloxamer)

[0100] Flavor Peppermint oil 0.90 Matrix forming polymer Gelatin Stabicaps™ 6.82

[0101] Shell Formulation

[0102] Component Function w / w (%) Sugar & Sweetener Glucose liquid 23.75

[0103] Sucralose 0.19 Film Forming Polymer Gelatin Stabicaps™ 30.52 Plasticizers Glycerol 21.01 Solvent Water 24.40 Flavor Peppermint oil 0.11 Colorant FD&C Blue #1 0.02

[0104] Example 2

[0105] Fill Matrix Formulation

[0106] Component Function w / w (%) Sugar Glucose liquid 24.46

[0107] Sucrose granular 24.60 Sweetener Sucralose 0.63

[0108] Acesulfame k 0.99 Polymer modifier Citric acid, anhydrous 0.33 Solvent Water 29.75 Polymeric Surface-active Kolliphor RH40 (Polyoxyl 2.69 agents 40 castor oil))

[0109] Kolliphor P 188 7.16 (Poloxamer)

[0110] Flavor Orange flavor 0.7 Matrix forming polymer Gelatin Stabicaps™ 7.07

[0111] Example 3

[0112] Fill Matrix Formulation

[0113] Component Function w / w (%) Sugar Glucose liquid 22.79

[0114] Sucrose granular 23.78 Sweetener Sucralose 0.91

[0115] Acesulfame k 2.10 Polymer modifier NA 0 Solvent Water 29.21 Polymeric Surface-active ... 0 , IN /

[0116] agentsFlavor Strawberry / Grape Flavor 0.24 Matrix forming polymer Gelatin Stabicaps™ 5.86

[0117] Shell Formulation

[0118] Component Function w / w (%) Sugar Glucose liquid 13.43 Sugar alternative Xylitol 7.67 _ Sucralose 0.25 Sweetener .

[0119] Acesufame Kd1.0n0 Film Forming Polymer Gelatin Stabicaps™ 29.74 Plasticizers Glycerol 20.15 Solvent Water 27.24 Flavor Grape Flavor 0.50 Colorant FD&C red and blue 0.06

[0120] Example 4

[0121] Fill Matrix Formulation

[0122] Component Function w / w (%) Sugar Glucose liquid 24.73

[0123] Sucrose granular 24.85 Sweetener Sucralose 0.20

[0124] Acesulfame k 0.20 Polymer modifier Citric acid, anhydrous 1.11

[0125] Water 32.38O venPropylene glycol 8.03 Polymeric Surface-active ... 0 I I 'I II

[0126] agents

[0127] Flavor Mint Flavor 0.03 Matrix forming polymer Gelatin Stabicaps™ 7.13

Claims

CLAIMS1. A chewable soft gelatin capsule comprises a shell composition, wherein the shell composition comprising:a. about 20% to about 35% by weight of the shell composition of bio-polymers;b. about 8% to about 35% by weight of the shell composition of one or more plasticizers; c. about 15% to about 35% by weight of the shell composition of one or more sugars or sugar alternatives;d. about 0.1% to about 5% by weight of the shell composition of a sweetener; and e. about 10% to about 40% of the shell composition by weight of one or more solvents.

2. The shell composition of claim 1, comprising: about 1% or less than 1% by weight of flavoring agents and colorants.

3. A chewable soft gelatin capsule of claim 1 or 2, further comprising a matrix composition, wherein the matrix composition comprising:a. about 0.05% to about 20% by weight of the matrix composition of at least one active pharmaceutical ingredient;b. about 5% to about 12% by weight of the matrix composition of bio-polymers;c. about 30% to about 60% by weight of the matrix composition of sugars or sugar alternatives;d. about 0.1% to about 5% by weight of the matrix composition of sweeteners;e. up to about 15% by weight of the matrix composition of polymeric surface-active agents; andf. about less than 2% of flavoring agents.

4. The chewable soft gelatin capsule of claim 3, wherein the polymeric surface-active agents comprise one or more non-ionic surfactants.

5. The chewable soft gelatin capsule of claim 4, wherein said one or more non-ionic surfactants comprise a combination of one or more kolliphor compounds.

6. The chewable soft gelatin capsule of claims 3 to 5, wherein the polymeric surface-active agents comprise one or more complexation agents.

7. The chewable soft gelatin capsule of claim 6, wherein said one or more complexation agents comprise up to about 15% of cyclodextrins.

8. The chewable soft gelatin capsule of claims 3 to 7, wherein the polymeric surface-active agents comprise one or more high molecular weight polymers.

9. The chewable soft gelatin capsule of claim 8, wherein said one or high molecular weight polymers comprise up to about 15% of polyethylene oxides.

10. The chewable soft gelatin capsule of claims 3 to 9, wherein the matrix composition further comprising: about 1% by weight of the matrix composition of polymer modifiers of lactic acid, fumaric acid, citric acid, tartaric acid, or a combination thereof.

11. The chewable soft gelatin capsule of claims 3 to 10, wherein said at least one active pharmaceutical ingredient is about 1%, 1.5%, or about 15% by weight of the matrix composition.

12. The chewable soft gelatin capsule of any preceding claim, wherein the shell composition comprising:a. about 30% by weight of the shell composition of a bio-polymer;b. about 21% by weight of the shell composition of a plasticizer;c. about 24% by weight of the shell composition of a sugar;d. about 0.2% by weight of a sweetener; ande. about 24% of the shell composition by weight of water.

13. The chewable soft gelatin capsule of claims 3 to 12, wherein the matrix composition comprising:a. about 2% by weight of the matrix composition of at least one active pharmaceutical ingredient;b. about 7% by weight of the matrix composition of a bio-polymer;c. about 24% by weight of the matrix composition of glucose;d. about 24% by weight of the matrix composition of sucrose;e. about 2.5% by weight of the matrix composition of sweeteners;f. about 12% by weight of the matrix composition of polymeric surface-active agents; g. about less than 1% of the matrix composition of a flavoring agent;h. about less than 1% of the matrix composition of a polymer modifier; andi. about 30% of the matrix composition of a solvent.

14. The chewable soft gelatin capsule of any preceding claim, wherein the bio-polymers comprise one or more modified gelatin polymers.

15. The chewable soft gelatin capsule of claim 14, wherein said one or more modified gelatin polymers comprise enzymatically treated gelatin, digested gelatin, or a combination thereof.

16. The chewable soft gelatin capsule of any preceding claim, wherein said one or more plasticizers comprise glycerol, sorbitol, mannitol, maltitol, xylitol, ora combination thereof.

17. The chewable soft gelatin capsule of any preceding claim, wherein said one or more sugar or sugar alternatives comprise glucose, sucrose, polysaccharides, glucose liquid, sucralose, or a combination thereof.

18. The chewable soft gelatin capsule of any preceding claim, wherein said one or more sweeteners comprise sucralose, acesulfame potassium, or a combination thereof.

19. The chewable soft gelatin capsule of any preceding claim, wherein said one or more solvents comprise purified water.

20. The chewable soft gelatin capsule of claims 3 to 19, further comprising: one or more taste suppressors at about 0.5% to about 3% by weight of the matrix composition, wherein said one or more taste suppressors comprise one or more of sodium acetate, sodium chloride, and sodium saccharin.

21. A method of manufacturing the chewable soft gelatin capsule of claim 1, comprising the steps of:a. preparing a shell composition by heating and homogenizing one or more bio-polymers, plasticizers, sugars, sugar alternatives, and sweeteners, optionally incorporating one or more flavoring agents and colorants;b. preparing a matrix composition by incorporating at least one active pharmaceutical ingredient with one or more sugars, sugar alternatives, sweeteners, polymeric surfaceactive agents, and flavoring agents to form a homogeneous mixture;c. encapsulating the homogeneous mixture within the shell composition through a rotary die process;d. drying the encapsulated homogeneous mixture to form the chewable soft gelatin; and e. optionally, conducting one or more post-production activities on the chewable soft gelatin to achieve desired physical and organoleptic attributes.