Description:FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
And
THE PATENTS RULES 2003
COMPLETE SPECIFICATION
(See section 10: Rule 13)

1. Title of the Invention
Gummesule Dosage Form for the Improvement of Bioavailability and Enhanced Patient compliance

2. Applicant (s)
(a) Name: Softgel Healthcare Pvt Ltd
(b) Nationality: Indian
(c) Address:

3. Preamble to the Description
The following specification particularly describes the invention and the manner in which it is to be performed
Technical Field
Described herein is a novel dosage form termed Gummesule suitable for chewing, sucking, or buccal dilution and particularly relate to a chewable, edible soft capsule comprising inner gummy fillings, their preparation methods and methods of treating individuals in need of such treatment with such dosage form. In particular, the present invention is at the intersection of taste and technology that combines the delectable goodness of gummies with the cutting-edge efficiency of softgels, giving birth to a new era of medicinal and nutritional delivery technology.
Background of the Invention
The oral route is the most common route for administering medicines as it is the most convenient and is easy to handle, making it the first choice for clinicians and most patients. Moreover, many drugs are well suited to be administered orally using different types of dosage forms, including liquids, tablets and soft gelatin capsule.
Despite their advantages, they are challenging to formulate if the active substances have poor dissolution rates or low bioavailability. Another main drawback associated with the solid oral forms is the swallowing difficulties encountered by some patient populations (e.g., paediatrics and geriatrics). It is extremely difficult for most people to swallow any of these oral dosage forms without supplemental water. In the fast-paced world, it is frequently inconvenient or messy to have to take supplementary water with oral medicaments. Certain medical conditions, such as Parkinsonism or other neurological states, make it difficult to swallow oral dosage forms, even with supplemental water. Additionally, swallowing oral dosage forms intact implicates a complex system of variables involved in gastrointestinal dissolution of dosage forms and absorption of drugs. Although liquid dosage forms are easy to swallow, they suffer from stability issues and dosing errors.
The formulation of a drug into Chewable dosage forms —e.g., chewable tablets, gummies, gums and lozenges are gaining attention due to their ease of administration, portability and safety. Chewable dosage units are of value to competent patients such as paediatric, geriatric and involuntary patient populations as an alternative to tablets or capsules that must be swallowed whole. As water is not required for their administration, there is a benefit of convenience when dosing.
Chewable tablet dosage forms may be preferred over conventional tablets and capsules when the required dose is high and the dosage form would be too big to pass through the oesophagus. Moreover, chewable tablets are not constrained by size, as they are designed to be chewed before they are swallowed. Additionally, as they disintegrate in the mouth, part of the drug dissolves in the saliva and is consequently absorbed through the buccal cavity, avoiding the first-pass effect and increasing the drug’s bioavailability.
The texture of a chewable dosage unit form is an important factor in the acceptance of oral dosage forms by patients in need of medication. The appropriate chewable tablet can also address texture problems caused by dry dusty, granular, and pulverate properties of many pharmaceutical ingredients. These formulations tend to lack certain organoleptic properties and are perceived by many patients as being dry, gritty, dusty, and/or bad tasting. Moreover, these formulations have been reportedly associated with incidents involving tooth damage or denture breakage resulting from excessive tablet hardness and oesophageal irritation.
Another important challenge associated with Chewable tablet is that the requirement of large amounts of sweeteners and flavouring agents to load chewable tablets with drugs having unpleasant or pungent tastes (e.g., bitter taste). Chewable tablets are hygroscopic and thus, must be stored in a dry place in airtight containers.
Chewable gels, a multiple unit dosage form, could be a suitable alternative; Soft-chewable gel dosage units, having a soft texture, pleasant mouth feel, and palatable taste with adequate flavouring agents, provide a solution to such problems. In addition, these features can address the problem of the disagreeable taste of many active pharmaceutical ingredients. However, chewable gels known in the art are difficult to manufacture (especially on a large scale) and/or suffer from an inability to consistently satisfy generally accepted regulatory standards. Further, many active pharmaceutical ingredients have tastes that are strongly disagreeable, something which manufactures of known chewable gels have failed to overcome. Therefore, there is a requirement for pleasant tasting chewable gels that: include active pharmaceutical ingredients; are capable of commercially viable manufacture; and consistently satisfy generally accepted regulatory standards.
These chewable gel formulations can be produced using different pharmaceutical methods, depending on the type of dosage form being made. However, most of these processes are complex, involving multiple unit operations. Many of the excipients utilize for formulating the chewable dosage forms ie. Pectin having a higher melting point. Hence processes involving heating at high temperature may not be suitable for thermolabile medicaments such as Vitamins, hormones, proteins and peptides.
Gummy dosage forms, a homogenous molten base dosage form, could be an another alternative; they are particularly effective for enabling compliant dosing in children, as well as geriatric adults, as these forms provide a palatable, chewable base, can incorporate APIs, and have low intrinsic taste response. However, while gummy dosage forms provide the basis for effective dosing of active ingredients to children (and geriatric patients), the preparation of stable gummy dosage forms including certain base ingredients (in particular, certain natural base ingredients) has been challenging. For example, the inclusion of honey in significant amounts commonly leads to stickiness, syneresis and/or other negative textural properties.

Considering the high amount of sugar that is used to make gummies, it poses a large threat to consumers. Gummies pose a serious threat to children, as they are addictive due to their high sugar content. Most studies have also pointed out that excessive sugar increases the chances of liver disease and some types of cancer. Gummies are often loaded with fillers and artificial food dyes that are harmful to health but provide an appealing texture and taste. Although sugar-free variants are available, replacing sugar with citric acid would be harmful to the enamel that guards your teeth.

Chewable soft capsule could be a suitable alternative; Chewable soft capsule is a kind of rising dosage form because of its advantages such as the dosage form provides higher bioavailability, good airproof performance, drug content accuracy and has elegant appearance. In comparison with common swallowable soft capsules in industries of food or pharmaceutics, chewable soft capsules (chewing type soft capsules) have improved chewiness of capsule shell so that they can be bitten and chewed in mouth, and have no poor taste of contents in common soft capsules.
While soft chewable capsules provide an effective dosing system, user acceptance has been limited by the organoleptic properties of the capsules, which are often criticized for being leathery or rubbery. Chewable softgels often have a distinguishable difference between the coating and the filling in terms of texture and mouthfeel. Some users experience difficulty consuming the chewed pod after the internal filling has been released. Additionally, chewable softgels tend to harden over time.
Further the chewable soft capsule has some challenges which is difficult to resolve including stability problems such as leakiness, syneresis and disintegration of capsule structure during storage period, chewability, mouth feel and therefore, the client acceptance. Chewable soft capsules with high end water content typically have poor storage performance, sticking to one another in bulk packaging and often melting or leaking during storage.
The present inventors thoroughly observed and understood the issues and limitations associated with each type of conventional chewable dosage forms ie. chewable tablet, chewable gel, gummy and chewable soft capsule. Hence, the primary objective of this present invention is to address these issues and limitations and give a solution for long term unmet need for an ideal chewable dosage form.
An ideal chewable dosage has an undistinguishable difference between the coating and the filling in terms of texture and mouthfeel. Further the dosage form should not display stability problems such as leakiness, syneresis and disintegration of dosage form during transportation and storage period and should be suitable for all type of manufacturing processes. The dosage form should have a pleasant chewing experience and a complete or near complete dissolution in a short period of time in the oral cavity.
While keeping the above-mentioned points, the present inventor has obtained a novel dosage form through original research and numerous experiments. The present inventors conducted many trials and further in result, they developed a chewable soft capsules having desirable organoleptic properties comprising inner gummy filling material in which the capsule shell and gummy dosage form can be chewed, sucked or slowly dissolved in the mouth to release the active ingredient with pleasant-tasting from refreshing liquid or semisolid or solid or matrix or hydrogel type gummy fillings.
Surprisingly, the present invention offers a chewable soft capsule dosage system having improvised capsules' organo-leptic properties which are not as being leathery or rubbery and enhanced higher user acceptance.
The present inventors termed the current invention as Gummesules because it combines the delectable goodness of gummies with the cutting-edge efficiency of softgels, giving birth to a new era of nutritional delivery technology. This innovative fusion of flavors and science brings the best of both worlds, combining the captivating flavors and chewable delight of gummies with the sleek efficiency and consistent dosing of softgels.
Object of the Invention
The present disclosure provides an edible, chewable soft capsule generally comprises an inner gummy filling encapsulated in a soft capsule outer sheath termed as Gummesules.
In one embodiment, the object of the invention is to formulate Gummesules which are apposite for all type of medicaments including high potent drugs, high dose drugs, thermolabile drugs and moisture sensitive drugs. The inventive manufacturing process and composition of the present invention provide a novel platform technology of ideal chewable dosage form suitable for all type of medicaments.
While conventional gummies often resemble candy, Gummesule restore the psychological aspect of adhering to proper dosage. Gummesule remain intact, mess-free, and stable, making them an ideal companion for the busy lifestyle. Differing from traditional gummies, Gummesule presents flexible packaging choices, as shape and size remain constant.
For gummies, the depositing is possible only in 95° C ± 5° C. The active content may degrade at this high temperature and due to this, high overages required for gummies. Whereas for Gummesules, the filling can be done in 40° C ± 5° C, so that the active content is protected, and regular overages are suitable for Gummesules. Gummesules can be made in clear transparent, colored transparent, and in opaque forms.
In one particular embodiment, the present invention is directed generally to an Gummesules which can offer precise drug dosing, ensuring accuracy even at low to ultra-low drug concentrations, a feature not found in conventional chewable dosage form.
In another embodiment, the object of the invention is to formulate Gummesules which are more convenient for patients who have difficulty in swallowing, especially children or the geriatric adults.
Another object of the invention is to prepare Gummesules which can mask the unpleasant odor and taste of the drugs and provide better patient acceptance through pleasant taste.
The present invention provides a composition for active ingredients in Gummesules dosage form that are stable during storage under ambient conditions.
Another object of the invention is to provide chewable dosage form with enhanced lusciousness compare to conventional oral dosage forms, such as conventional tablets and capsules.
In another particular embodiment, the present invention is directed generally to an Gummesules which are soft, elastic, easy to chew with a pleasant mouth feel and then swallowed easily. It does not require water to swallow, it can be taken at any time and place.
In another particular embodiment, the present invention is directed generally to a dosage form which has improved bioavailability (which increases dissolution) bypassing dissolution, and the faster rate of absorption.
In another embodiment, the present invention is directed Gummesules can easily chew in the mouth, so the drugs are quickly absorbed and do not pass through the digestive system.
This invention provides chewable soft gel compositions that minimize or reduce the traditional user's complaints regarding a perceived major difference in texture between the inner filler material and the soft chewable capsule shell or sheath that is a result of the current technology. Therefore, this invention describes chewable soft capsule compositions encapsulated inner gummy fill material with homogeneous, controllable mouth-feel for the whole capsule.
In one embodiment of the invention, the gummy composition (inner fill material) is made from a hydrophilic matrix comprising a first gel-forming polymer and its oligomers or hydrolysates, polymer modifier that can control the texture, viscosity, and melting point of the matrix portion of gummy composition and the sweetener.
Depends on the type of medicament selected and the desirable profile of the composition, the inner gummy fillings of Gummesules may additionally include hydrophilic polymer, hydrophilic filler, hydrating agent and a water. The biological active ingredient may be present in the form of dispersed and dissolved state within the inner gummy fillings.
In another embodiment, the gummy composition (inner fill material) may be in the different physical states not limited to liquid, semi-solid and solid materials encapsulated in a soft capsule outer sheath.
The gummy fill material also includes an active ingredient that is to be delivered to the user, and optionally contains flavouring agent, sweetener, and/or a taste-masking agent.
In addition, the outer sheath of Gummesules comprises a polymer modifier, along with the second gel-forming polymer composition, sweetening agent and plasticizer. Such a combination has the benefit of providing a stable composition where mass transfer between the shell and the gummy matrix portion is reduced due to the structural similarity between the gummy matrix composition and the shell.
In some embodiments, the outer sheath of chewable soft capsule is formed of a second hydrophilic polymer, hydrophilic filler and a water. The selection and quantity of excipients for outer sheath material may differ according to the requirement of ideal profile for an individual active ingredient.
One or both of the first and second gel-forming polymer may be a same polymer that exhibits a bloom in a predetermined range. Preferably both first and second gel-forming polymer is gelatin.
The present invention is directed generally to an Gummesules which can be available in different sizes, shapes, colors, and flavors. The current invention provides Gummesules which are hermetically preserved, sealed and ensure leak free chews.
A method of making a soft capsule is also encompassed by the present invention. The method generally includes the step of combining a gel-forming polymer with a polymer modifier, incubating the combined gel-forming polymer, hydrophilic polymer and polymer modifier to form an inner gummy fill material; and, encapsulating the inner gummy fill material into a chewable soft capsule outer sheath.
These and other embodiments and advantages are contemplated by the present invention, which is set forth in detail below.
Detailed Description of the Invention
The invention now will be described more fully hereinafter through reference to various embodiments. These embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Indeed, the invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. As used in the specification, and in the appended claims, the singular forms “a”, “an”, “the”, include plural referents unless the context clearly dictates otherwise.
As used in this specification, the term “about” refers to a variation or tolerance in a stated amount, concentration, ratio or proportion, preferably defined as being no more than 20%,10%, 5%, 2% or 1% above or below a stated amount, concentration, ratio or proportion.
The term “pre-gastric absorption” includes buccal, sublingual, oropharyngeal and esophageal absorption. Medicaments absorbed by such pre-gastric absorption pass straight into the systemic circulatory system thereby avoiding first pass metabolism in the liver. Accordingly, bioavailability of agents absorbed in this way may also be increased. This means that the dose of such agents may be reduced while still producing the desired beneficial effects and this decrease in dose may result in a corresponding reduction of unwanted side effects.
A “chewable” means that the composition is malleable and/or ductile at room temperature. Accordingly, the composition is not totally hard and can be chewed, but without substantially crumbling when compressed. The composition is not totally elastic, although it may exhibit some springiness in at least some embodiments.
A "gummy" or "gummy dosage form" as used herein is understood to refer to a confectionary that can be defined by its compositional nature, as otherwise described herein, and also by its chewy texture and mouthfeel. Gummy bears, gummy worms, and other gummy candies are known in the art, and a person of ordinary skill in the art would understand the term "gummy" to refer to a composition having such texture and mouthfeel. It is noted that the gummy dosage forms disclosed herein may vary somewhat in texture and mouthfeel. All such textures and mouthfeels are intended to be included within the general definition of "gummy."
The soft capsules designed to be broken up in the mouth and completely or nearly completely dissolved by chewing, that is, the so-called “chewable soft” capsule. Such true “chewable soft” capsules are a type of soft capsule that is particularly distinguished by both a pleasant chewing experience and a complete or near complete dissolution in a short period of time in the oral cavity.
A term “gel” refers to a two-phase colloidal system comprising a liquid and a solid in the form of thickened liquid, semi-solid or solid. A gel also can refer to a composition that is either physically cross-linked by virtue of entangled polymer chains, or chemically cross-linked by virtue of covalent bonds such that it swells, but does not dissolve, in the presence of liquid. A gel typically is obtained by use of a gelling agent.
The term "polymer" used herein includes both homopolymer and copolymer. A homopolymer is a polymer obtained by polymerizing one type of monomer, whereas a copolymer is a polymer obtained by polymerizing two or more types of monomers. "Block copolymer" refers to a copolymer in which like monomer units occur in relatively long, alternate sequences on a chain.
As used herein, the terms “gel-forming polymer” and “gel-forming composition” refer to any natural or synthetic polymeric material or partial hydrolysate of a polymer that can form a gel when appropriately dissolved or dispersed in water or aqueous media.
The following embodiments exemplify the relative amounts of the components that may be utilized. All percentages are on a weight/weight basis (the weight of the specific component relative to the total weight of the chewable soft capsule composition).

In one embodiment, the chewable soft capsule generally includes, an inner gummy fill material encapsulated in a soft capsule sheath, wherein the gummy inner fillings is present in various forms including solid (matrix), semi-solid (hydrocolloid), liquid and hydrogel form. The nature of physical form of inner gummy fillings may command the type and quantity of excipients. The type of excipient which are significant to design a physical form of gummy inner fillings are gel forming polymer, hydrophilic fillers, polymer modifier, hydrophilic polymer, hydrating agent and water.
Various challenges associated with chewable soft capsule dosage form such as dosing and stability issues that occur during storage and handling conditions. These challenges are generally resolved by modifying the concentration of gel forming polymers, hydrophilic polymer, hydrophilic fillers, polymer modifiers, plasticizer and water content.
In one embodiment of the invention, the gummy composition (inner fill material) is made from a hydrophilic matrix comprising a gel-forming polymer and its oligomers or hydrolysates, hydrophilic fillers, hydrophilic polymers, sweetening agents, hydrating materials in presence of a polymer modifier that can control the texture, viscosity, and melting point of the matrix portion of gummy composition.
Further the gummy composition (inner fill material) comprises colouring agents, buffering agents, sweetening agent and flavouring agents.
In another embodiment of the invention, the inner gummy filling materials generally comprise hydrocolloid systems, which can comprise, in some embodiments, one or more hydrophilic fillers, one or more gel-forming polymers, polymer modifiers and a hydrating material (water source). Optionally, the hydrocolloid system can include one or more further ingredients, such as buffering agents, colouring agents, and/or flavouring agents.

In addition, the outer sheath ie. Chewable soft capsule comprises hydrophilic polymers, polymer modifier, sweetening agents and plasticizer along with the second gel-forming polymer composition. Such a combination has the benefit of providing a stable composition where mass transfer between the chewable soft capsule shell and the inner gummy filling material is reduced due to the structural similarity between the inner gummy filling material and the outer capsule shell sheath.
Examples of gel-forming polymer include proteins such as different types of gelatin from different sources. Specific examples for both first and second gel forming polymers are: acid and lime bone bovine gelatine; pig bone gelatin; skin pig gelatin; skin bovine gelatin; and fish gelatin. Other examples of gel-forming compositions are of polysaccharide nature. Specific examples are: sodium and calcium alginate; natural and modified starch and starch hydrolysates; pectins and amylopectins; and cellulose derivatives, such as hydroxypropyl-methyl cellulose, and carboxymethyl cellulose, and salts thereof.
A gel-forming composition can be a hydrophilic filler, alone or in combination with its building units, its oligomers, or hydrolysate. Non-limiting examples of gel-forming polymers that may be included in the present invention for use as a gummy composition according to the present disclosure include: carrageenan, gellan gum, locust bean gum, gum arabic, xanthan gum, methylcellulose, agar, konjac, alginates, and combinations thereof (including single, binary, tertiary, or quaternary blends).
The Gel-forming polymers useful in a present invention according to the present disclosure include long chain carbohydrates (e.g., polysaccharides) as well as various proteins. The hydrophilic filler preferably is configured to thicken and form a gel upon hydration (with or without heating).
Depending upon the specific formulation, the first and second gel-forming polymers may be either identical to each other or differ in their chemical compositions, bloom values and/or amounts. Likewise, the first and second plasticizers may be identical or differ in their compositions and/or amounts.
In another embodiment, the soft capsule outer sheath has a matrix formed of a gel forming polymer ie. Gelatin that exhibits a bloom in the range of about 0 to about 150 and preferably the matrix includes a gelatin exhibiting a Bloom in the range from about 20 to about 250.
In yet another embodiment, a sheath that exhibits a bloom in the range of about 100 to about 150.
In one particular embodiment, the chewable soft capsule sheath includes a gelatin exhibiting a bloom in the range of about 0 to about 250.
In yet another embodiment, the chewable soft capsule sheath includes a gelatin that exhibits a bloom in the range of about 80 to about 250.
In yet another embodiment, the inner gummy material includes a gelatin exhibiting a bloom in the range from about 20 to about 120.
In yet another embodiment, the inner gummy material includes a first gel forming polymer ie. gelatin exhibiting a bloom in the range from about 40 to about 100.
In yet another embodiment, the inner gummy material includes a gelatin exhibiting a Bloom in the range from about 40 to about 80.
The inner gummy fill material composition can comprise about 5% to about 20%, about 10% to about 15%, or about 5% to about 10% w/w of the gel forming polymer(s).
The soft capsule outer sheath composition can comprise about 25% to about 50%, about 35% to about 45%, or about 30% to about 40% w/w of the gel forming polymer(s).
The hydrophilic fillers useful in the present invention according to the present disclosure include saccharides or saccharide derivatives as otherwise described herein. In exemplary embodiments, hydrophilic fillers can include oligofructose, dextrins, monosaccharides (e.g., fructose or glucose), disaccharides (e.g., palatinose, Sucralose or sucrose), hydrogenated carbohydrates, also known as sugar alcohols (e.g., polyols, monosaccharide alcohols, disaccharide alcohols, or oligosaccharide alcohols), and syrups (e.g., glucose syrup or fructose syrup). The hydrophilic fillers further may be a synthetic material, such as soluble fibers (e.g., polydextrose).
The chewable composition wherein the composition comprising hydrophilic filler is selected from the group consisting of Rhamnose, ribose, Glucose, fructose galactose, mannose, arabinose, xylose, erythrose, and others. Sucrose, isomaltulose, lactose, maltose, trehalose, and others. Raffinose, stachyose, fructo-oligosaccharides (FOS), arabino-oligosaccharides (AXOS), and others. Amylose, amylopectin, and modified starches, Deoxy sugars, Methylated monosaccharides, Uronic acids, Aldonic acids, Aldaric acids, Amino sugars. Lecithin, Mono- and diglycerides, Monoglycerides, Glyceryl-Lacto esters of fatty acids, Ethoxylated Mono- and Diglycerides, DATEM, Sodium stearoyl lactylaye, Propylene Glycol Mono and Diesters of Fats and fatty acids, Whey protein including Collagen, egg whites, gelatin (from animal collagen), whey, polysorbates, Cetearyl alcohol, Ceteareth 20, Behentrimonium Methosulfate, Butylene glycol, Casein and Gum Arabic and proteins.
The inner gummy fill material composition can comprise about 0.05% to about 2%, or about 0.1% to about 1%, or about 0.05% to about 0.5% w/w of the hydrophilic filler(s), particularly one or more saccharides or saccharide derivatives.
The soft capsule outer shell composition can comprise about 0.1% to about 3%, or about 1% to about 2%, or about 0.1% to about 0.5% w/w of the hydrophilic filler(s), particularly one or more saccharides or saccharide derivatives.

The soft, chewable composition wherein the composition comprising the hydrophilic polymer is selected from the group consisting of (Poly(acrylamide), Poly(2-acrylamido-2-methylpropanesulfonic acid sodium salt), Poly(N,N-diethyl acrylamide), Poly(N-isopropyl acrylamide), Poly(N,N-dimethyl acrylamide), Poly(N,N-dimethylaminopropyl acrylamide), and Poly(N-phenethyl methacrylamide), Poly(methacrylic acid) and its salt, Poly(a-propylacrylic acid), Poly(2-aminoethyl methacrylate), Poly(2-hydroxyethyl methacrylate), Poly(N,N-dimethylaminoethyl methacrylate, quaternized with a-bromoisobutyryl bromide), Poly(N,N-dimethylaminoethyl methacrylate, quaternized with tert-butyl bromoacetate), (Poly(ethylene glycol) or Poly(ethylene oxide), a,?-bis(hydroxy)-terminated, Poly(ethylene glycol), with (Bisphenol A-co-epichlorohydrin) linker, Poly(ethylene glycol), a-dibenzylmethylene-terminated, Poly(ethylene glycol), (a-dimethylamine, ?-hydroxy)-terminated, Poly(ethylene glycol), (a-dimethylamine, ?-methoxy)-terminated, Poly(ethylene glycol) benzyl ether, Poly(ethylene glycol) ethyl ether, Poly(ethylene glycol) dimethyl ether, Poly(ethylene glycol) methyl ether, (initiator: methoxyethanol-based) and Poly(ethylene glycol) methyl ether, (initiator: 2-methoxypropanol-based), (Poly(4-styrene sulfonic acid), Poly(4-styrene sulfonic acid cesium salt), Poly(4-styrene sulfonic acid sodium salt), P (Poly(N-vinyl acetamide), Poly(vinylamine) and Poly(N-vinyl pyrrolidonoe), Poly(N-vinyl imidazole, quaternized with methyl iodide), Poly(N-vinyl imidazole, quaternized with bis[2,2-bipyridine-N,N']-Osmium(II) complex), Poly(N-vinyl imidazole, quaternized with bis[2,2-bipyridine,4,4-dimethoxy-N,N']-Osmium(II) complex), Poly(N-vinyl imidazole, quaternized with bis[2,2-bipyridine-N,N']-Ruthenium complex), Poly(2-vinyl pyridine, quaternized with methyl bromide), Poly(2-vinyl pyridine, quaternized with methyl iodide), Poly(ethylene imine), Poly(L-histidine), Poly(methyl vinyl ether), Poly(oxymethylene), Poly(L-proline) Poly(tetrahydrofuran) and Polyvinyl alcohol.
The inner gummy fill material composition can comprise about 20% to about 30%, about 10% to about 15%, or about 5% to about 10% w/w of the hydrophilic polymers.

The hydrating materials used in the mixture of hydrogel and polymeric system can include any variety of materials configured to donate water to the gel-forming polymer. The hydrating material particularly can be substantially pure water; however, the hydrating material may be an aqueous composition including one or more additives, such as a syrup, a fruit juice, or a flavouring liquid.
The Gummesule composition can comprise about 1% to about 20%, about 10% to about 15%, or about 15% to about 20% w/w of the hydrating materials.

The inner gummy fillings contain stabilizing agent and thickening agents including but not limited to Arabinogalactan, beta-Cyclodextrin hydrate, Bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate, Casein, Guar gum, Hydroxypropyl starch, Locust bean gum, Polyacrylamide, Polydextrose, Polyvinylpyrrolidone cross-linked, Potassium alginate, Gelatin, Pectin, Starch, Agar, Carrageenan, Guar Gum, Gum Arabic (Acacia Gum), Locust Bean Gum (Carob Gum), disodium edetate, Xanthan Gum and starch acetate.
A chewable soft capsule outer sheath exhibiting organo-leptic properties that are appropriate for use as a chewable dosage form for delivering therapeutic, diagnostic, and/or dietary agents is set forth herein. The organo-leptic properties of the soft capsule, such as, for example, texture, and chewiness, are enhanced by the polymer modifier included in the capsule formulation. In addition, the polymer modifier enhances the physical and/or chemical properties of the gel-forming polymers that are used to form the capsule matrix and/or sheath, thereby facilitating the processing of the outer sheath soft capsule.
The polymer modifier used to form the matrix of the soft capsule of the present invention generally includes a carboxylic acid. In one embodiment, the polymer modifier used to form the matrix of the soft capsule is selected from lactic acid, fumaric acid, tartaric acid, citric acid, glycolic acid, and combinations thereof.

The plasticizer used to form the matrix and/or sheath of the soft capsule may include a polyol. In another particular embodiment, the soft capsule is formed using a plasticizer selected from are glycerol, sorbitol, maltitol, xylitol, alcohol, glycol (eg, propylene glycol), lanolin, wool fat, liquid paraffin, mineral oil, petrolatum, benzylphenylformate, chlorobutanol, diethyl phthalate, glycerin, polyethylene glycol, Propylene glycol, sorbitol, triacetin, benzylphenylformate, PLGA, methacrylic acid ester, phthalate ester, acetyltributylcitrate, acetyltriethylcitrate, castor oil, dibutyl sebacate, tributyl citrate, triethyl citrate, or theirs and combinations thereof.
The soft capsule outer shell composition can comprise about 10% to about 45%, about 20% to about 30%, or about 15% to about 25% w/w of plasticizers.
The concentration of active substance in the inner gummy material depends on the therapeutic conditions in which said composition is intended to be administered. It will be apparent to a person skilled in the art that said concentration will be lower in high potent drugs. The present invention provides a platform by which the high potent drugs can be administered without requiring higher amount of excipients hence avoiding the higher weight dosage form which is the disadvantage normally associated with conventional chewable dosage form.
The development of a successful formulation depends on selecting appropriate excipients. Many of the excipients used to prepare chewable dosage forms are similar to those used in conventional dosage forms. The key excipients in chewable tablets include flavouring agents and sweeteners because they are intended to be chewed, and it is necessary to mask unpleasant tastes.
Humectants include but not limited to Potassium Phosphate Dibasic, Sodium hexametaphosphate and Sodium phosphate monobasic.
The flavouring agents including but not limited to (+)- Borneol, 2-Acetonaphthone, 3,3,5-Trimethylcyclohexanol, 3,7-Dimethyl-7-hydroxyoctanal, 6-Methylcoumarin, Allyl cyclohexylpropionate, Allyl heptanoate, Allyl hexanoate, alpha-Amylcinnamaldehyde, Avocado Powder, Banana powder, Benzyl ether, Butyl butyryllactate, Cinnamaldehyde, Diethyl acetal, CIS-4-Decenoic acid, Cranberry powder, cyclamen aldehyde, D(+)-2-Octanol, Dimethyl benzyl carbinyl acetate, L-Lysine-L-aspartate, LinoleicAcid, Lycopene microencapsulated powder, Magnesium L-Threonate, Manganese gluconate, Medium chain triglyceride customization microencapsulated powder, Medium chain triglyceride MCT-A70 microencapsulated powder, Medium chain triglyceride MCT-A70-OS microencapsulated powder and Medium chain triglyceride MCT-CI70 microencapsulated powder, Medium chain triglyceride MCT-SM50 microencapsulated powder, Medium chain triglyceride MCT-CM50 microencapsulated powder, Microencapsulated Ferrric Pyrophosphate, Mixed tocopherol microencapsulated powder, Olive oil microencapsulated powder, pea protein concentrate, Pea protein isolate, PQQ DISODIUM SALT, Pyridoxine dipalmitate, Pyridoxine hydrochloride, Safflower seed oil microencapsulated powder, Silybum marianum Seed oil microencapsulated powder, Sunflower seed oil microencapsulated powder, Taurine, Thiamine hydrochloride, Vitamin B12, Yeasts, Riched selenium, Zinc lactate and a-tocopherol microencapsulated powder.
The soft capsule outer shell composition can comprise about 0.1% to about 1%, about 2% to about 4%, or about 1% to about 2% w/w of flavouring agents.
The inner gummy fill material composition can comprise about 1% to about 5%, about 2% to about 4%, or about 1% to about 2% w/w of flavouring agents.

The sweetening agents including but not limited to wherein the sugar is selected from the group consisting of monosaccharides, such as fructose, glucose and xylose, disaccharides, such as sucrose, trehalose and lactose, trisaccharides, polysaccharides, oligosaccharides, such as fructan and inulins, sugar alcohols, such as sorbitol, xylitol, lactitol and maltitol, and combinations thereof, the biopolymer is selected from the group consisting of gellan gum, konjac gum, modified starch, pectin, carrageenan, guar gum, xanthan gum, locust bean gum, agar, gum Arabic, alginate, cellulose and combinations thereof, the botanical powder is selected from the group consisting of tobacco powder, coffee powder, tea powder, herb powder, spice powder, cocoa powder and combinations thereof and the at least one botanical powder has at least one linear dimension of less than about 50 mesh.
The sweetening agents including but not limited to 18ß-Glycyrrhetinic Acid, Acesulfame, Alitame, Aspartame, Beta-phenylpropiophenone, Calcium Saccharin, Disodium Glycyrrhizate, Hydrogenated starch hydrolysate, Invertose and levan.
The term “saccharide” as used herein (including in relation to all compositions described herein) can encompass sugar, starch, and cellulose materials. A saccharide can be a monosaccharide, a disaccharide, an oligosaccharide, or a polysaccharide. Exemplary monosaccharides include glucose, fructose, and galactose. Exemplary disaccharides include sucrose, lactose, lactulose, maltose, trehalose, cellobiose, and chitobiose. Exemplary oligosaccharides include fructo-oligosaccharides, galactooligosaccharides, and mannan oligosaccharides. Exemplary polysaccharides include glucans, starches, celluloses, pectins, xylans, arabinoxylans, mannans, and galactomannans. Saccharide derivatives can include any material that is derived from a saccharide. In particular, saccharide derivatives may be formed by substitution of one or more hydroxyl groups on the compound to form, for example, amino sugars, acidic sugars, deoxy sugars, sugar alcohols, glycosylamines, and sugar phosphates. Non-limiting examples of sugar alcohols include erythritol, xylitol, ribitol, mannitol, sorbitol, volemitol, isomalt, maltitol, and lactitol. Saccharide derivatives can also encompass artificial sweeteners, such as sucralose.
The soft capsule outer shell composition can comprise about 10% to about 40%, about 20% to about 30%, or about 15% to about 25% w/w of flavouring agents.
The inner gummy fill material composition can comprise about 1% to about 4%, about 0.5% to about 2%, or about 0.5% to about 1% w/w of flavouring agents.
The Gummesule composition can comprise about 5% to about 35%, about 10% to about 30%, or about 16% to about 28% w/w of water for inner gummy fill material and 15% to about 50%, about 10% to about 40%, or about 35% to about 45% for soft capsule outer shell.

The Gummesule composition for both soft capsule outer sheath and gummy inner fillings can comprise up to about 4%, up to about 2%, or up to about 1% of colouring agents selected from the group consisting of water soluble, water insoluble and iron oxides and sunset yellow FCF.
The inner gummy filler material comprising active ingredients may be encapsulated into soft capsule outer sheath utilizing any encapsulating technology known in the art. For example, microcapsules can be formed using any of various chemical encapsulation techniques such as solvent evaporation, solvent extraction, organic phase separation, interfacial polymerization, simple and complex coacervation, in-situ polymerization, liposome encapsulation, and nanoencapsulation. Alternatively, physical methods of encapsulation could be used, such as spray coating, pan coating, fluid bed coating, annular jet coating, spinning disk atomization, spray cooling, spray drying, spray chilling, stationary nozzle coextrusion, centrifugal head coextrusion, or submerged nozzle coextrusion.
The "active ingredient" included within the gummy dosage forms disclosed herein can be any compound, composition, or like material that may be included in a dosage form for delivery to an individual to achieve any one or more of a desired nutritional purpose, medicinal purpose, and therapeutic purpose. The types of active ingredients incorporated within the disclosed gummy dosage forms include, but are not limited to, vitamins, minerals, phytonutrients (e.g., carotenoids, flavonoids, resveratrol, and glucosinolates), fibre, fatty acids, amino acids, polypeptides, and botanicals. Further, non-limiting examples of materials that may be included as an active ingredient include APIs, and non-limiting examples of APIs include nonsteroidal anti-inflammatory drugs (NSAIDs— e.g., ibuprofen, diclofenac, and naproxen), analgesics (e.g., acetaminophen, aspirin), antihistamines, decongestants, antitussives, expectorants, sleep aids, antibiotics, laxatives, anti-diarrheal, anthelmintics, antacids, anti-epileptic agents (e.g., sodium valproate, phenobarbital), antipyretic analgesics (e.g., acetaminophen, ibuprofen, ketoprofen, aspirin, isopropyl antipyrine, diclofenac sodium, Emorufazon, salicylamide, sasapyrine), psychotropic drugs (for example, perphenazine, chlorpromazine hydrochloride, hydroxyzine hydrochloride, hydrochloric acid Isopuramin, clotiazepam), antispasmodic agents (for example, Furopuropion, timepidium bromide), inotropic agents (for example, hydrochloric acid etilefrine) , antiarrhythmic agents (eg, disopyramide, mexiletine hydrochloride, hydrochloric acid aprindine), antihypertensive agents (eg, captopril), hyperlipidemia for agents (eg simvastatin, probucol), antitussive single agent (for example, citric acid pentoxyverine , dextromethorphan hydrobromide, guaifenesin), gout therapeutic agent (eg, colchicine), diabetes drugs (for example, hydrochloric acid buformin), antihistamines (eg, diphenhydramine hydrochloride, d- chlorpheniramine maleate, chlorpheniramine maleate , hydrochloric acid Toripurojin, dimenhydrinate, promethazine hydrochloride), allergy drugs (for example, methoxyphenamine), dental oral agents (for example, cetylpyridinium chloride), gastrointestinal function adjustment agent (for example, hydrochloric acid Bedanekoru), laxatives (eg, dioctyl sodium sulfosuccinate, vitamins (eg, ergocalciferol, alfacalcidol, fursultiamine, tocopherol acetate), and the like.

The present invention is especially suited to active substances that have an unpleasant taste and combinations of such actives. Such active substances can be food substances such as vitamins, mineral salts, oligo-elements, herbal extracts or also pharmaceutical substances selected from the group comprising analgesics such as aspirin, acetaminophen, acetaminophen with caffeine; non-steroidal anti-inflammatories such as ibuprofen, diclofenac, aceclofenac, fenoprofen, flurbiprofen, ketoprofen, naproxen and its alkaline metal salts, nimesulide, piroxicam and its salts; H2 antagonists such as cimetidine, ranitidine hydrochloride, famotidine, nizatidine, ebrotidine, mifentidine, roxatidine, pisatidine and aceroxatidine; anti-allergenic agents such as codeine and its hydrochloride, codeine and its phosphate, ebastine, clemastine and its fumarate, azatidine and its maleate, hydroxyzine and its pamoate and its hydrochlorides, chlorpheniramine and its maleates and tannates, pseudoephidrine and its sulphates and hydrochlorides, bromopheniramine and its maleate, loratidine, phenylephrine and its tannates and hydrochlorides, methscopolamine and its nitrates, phenylpropanolamine and its hydrochlorides, bromopheniramine and its maleate, terfenadine, acrivastine, astemizole, cetirizine and its hydrochloride, phenindamine and its tartrate, tripelennamine and its hydrochloride, cyproheptadine and its hydrochloride, cyproheptadine and its hydrochloride, promethazine and its hydrochloride, pyrilamine and its hydrochlorides and tannates; anti-migraine agents such as divalproex and its alkaline metal salts, timolol and its maleate, propanol and its halogen hydrates, ergotamine and its tartrate, caffeine, elitriptan, sumatriptan and its succinate, and active substances of the same therapeutic class; dihydroergotamine, its hydrogenates and mesylates, methsergide and its maleate, isomethepten mucate, dichloralphenazone; antiemitics such as meclizine and its hydrochloride, hydroxyzine and its hydrochloride and pamoate, diphenhydramine and its hydrochlorides; prochlorperazine and its maleate, benzquinamide and its hydrochloride, granisetron and its hydrochloride, dronabinol, bismuth subsalicylate, promethazine and its hydrochloride, metoclopramide and its halides/hydrates, chlorpromazine, trimethobenzamide and its hydrochloride, thiethylperazine and its maleate, scopolamine, perphenazine, ondansetron and its hydrochloride; antidiarrheals such as loperamide; antihistamines such as seldane, hismanal, relafen, tavist; antitussives, decongestants, axiolytics such as xanax; antipsychotics such as clozaril and ilaldon; antiemetics such as kytril and cesamet; bronchodilators such as bentolin and proventil; antidepressants such as prozac, zoloft, and paxil; ACE-inhibitors such as vasotec, capoten and zestril; anti-alzheimers agents such as nicergoline; and Ca11-antagonists such as procardia, adalat, and calan; anticholesterolemics such as lovastatin and pravastatin; cold and cough products such as dextromethorphan and its bromhydrate salts and guaifenesin and its hydrochloride salts; CoX-2 inhibitors; antiepileptic compounds; 5HT inhibitors such as sildenafil; proton pump inhibitors such omeprazole, pantoprazole, lanzoprazole, terbinafine; and macrolides such as chlarithromycine, roxythromicin, azythromycin and ketolides such as telithromycin, beta-lactamin, cephalosporin, fluoroquinolone, and quetiapine.
Further the examples of active ingredients useful in this application are: anti-asthmatic drugs such as salbutamol, theophylline; anti-epileptic drugs such as phenytoin; analgesics such as paracetamol, naproxen, ibuprofen, aspirin, meloxicam, and celecoxib; nonsteroidal anti-inflammatory drugs (NSAIDs); beta-lactam antibiotics such as amoxycillin; macrolide antibiotics such as azythromycin, and clarythromycin; mineral supplements, such as iron, potassium, calcium, magnesium supplements and salts thereof; and vitamins, such as vitamins C, B complex, A, E, K, and D; and other food supplements.
The concentration of the biological active in a soft capsule is at most 0.1% to 75%, preferably between .01% and 50%, and even more preferably between 0.1% and 40% by weight.
The present invention will be more readily understood by referring to the following examples which are given to illustrate the invention rather than to limit its scope.
Examples
Example 1—Exemplary formulations according to the present disclosure for Gummesules outer shell composition (Table 1 and 3) and Gummesule inner gummy Filling material composition (Table 2 and 4) were given below.

Table 1: Chewable soft capsule outer sheath Formulations
Ingredient % By weight
Gel forming Polymers 25-55
Plasticizer 5-40
Water 15-40
Active Ingredient 0.01-70?
Other Ingredients, e.g., flavors, sweeteners, and taste-masking known in the industry 0.01-10?

Table 2: Inner gummy filler Formulations
Ingredient % By weight
Gel forming Polymers 15-80
Polymer modifier 0.1-10
Plasticizer 5-40
Water 5-30
Active Ingredient 0.01-70?
Other Ingredients, e.g., flavors, sweeteners, and taste-masking known in the industry 0.01-15?

The gel-forming polymer of the above embodiment may be a gelatin that exhibits a bloom in the range of about 0 to about 150. The plasticizer may be a polyol, such, for example, glycerol, sorbitol, maltitol, xylitol, or combinations thereof. The polymer modifier may be a mono, di, or poly carboxylic acid. More specifically, the polymer modifier may be lactic acid, fumaric acid, tartaric acid, citric acid, glycolic acid or a combination of two or more of these acids.
Example 2.
Table 3: Chewable soft capsule outer sheath Formulations

S. No. Shell composition % w/w of Outer sheath
1 Gelatin 30 - 45%
2 Glycerin 15 - 30%
3 Sucralose 0.1 - 5%
4 Citric acid anhydrous micronized Powder 0.5 - 5%
5 Red iron oxide 0.05 - 1%
6 Yellow iron oxide 0.05 - 1%
7 Sunset yellow FCF 0.05 - 1%
8 Forest fruit flavour 0.1 - 3%
9 Purified water QS

Table 4: Gummesule inner gummy Filling material composition

Gummesules composition workable range
S. No. Raw Materials % of gummy inner fillings
A Fill composition
1 Active ingredients as per claim
2 Gelatin 6.0-10%
3 Glucose, Liquid 30.0-40%
4 Sucrose 30.0-40%
5 Fumaric acid 1.0-2.0%
6 Sucralose 1.0-5.0%
7 Citric acid Anhydrous Micronized Powder 1.0-2.0%
8 Acesulfame Potassium 0.5-1.0%
9 Disodium Edetate 0.2-1.0%
10 Flavours 0.05-1.0%

Procedure for the preparation of soft capsule outer sheath composition: Switch on the control panel and allowed the hot water circulation in gelatin melting tank to maintain the temperature of 80°C to 90°C. The gelatin melting tank was allowed to maintain inside product temperature at 70°C ± 5°C throughout process. Glycerin and Purified water were transferred (by retaining 2kg) (by retaining 5kg) into the gelatin melting tank after filtering through muslin cloth, switch on the stirrer and mix for 10 minutes. Purified water was taken in suitable SS vessel and Sucralose and Citric acid anhydrous micronized Powder were added and stirred manually mix for 5 minutes and the gelatin was added into gelatin meting tank and mixed for 10 minutes. The gelatin flakes were transferred into the gelatin melting tank and Switch on the stirrer and allow to mix for 10 minutes or till slight purging starts or till a creamy mixture is formed. Vacuum was applied initially and mixed at 70°C ± 5°C or till the gelatin flakes melt completely. The water-soluble colorants were dissolved in purified water and transferred into the gelatin melting tank. Glycerin was milled with Opacfying agent in colloid mill for 20 minutes and transferred the mixture into the gelatin melting tank. The vessel was rinsed with remaining quantity of Purified Water and transfer into gelatin melting tank. Switch on the stirrer for 30 minutes for uniform colour mixing. Vacuum was applied to remove the air bubbles.
A small quantity of gelatin mass was taken and examined for the presence of air bubbles, homogeneity of gelatin mass and uniformity of color mixing.
Procedure for the preparation of Gummesule Fill Composition:
The gelatin was taken into SS container with purified water and heated it for 60-70°C for 30 minutes until gelatin melts. This solution is called gelatin base solution. Components such as glucose liquid, sucrose, Fumaric acid and purified water were taken separately into a suitable SS container, heat it for 50-60°C for 30 minutes until complete dissolution. The temperature was maintained at 50- 60°C throughout the process. Components such as sucralose, citric acid anhydrous micronized powder, disodium edetate, Acesulfame K and purified water were added in a separate SS Container and mixed for 10 minutes till uniform dispersion was obtained. This solution is called sweetener solution. The sweetener solution was slowly added into step 2 solution and mix for 10 minutes. The gelatin base solution was slowly added into step 2 solution and mix for 20 minutes. Finally, the drug solution was added into step 2 solution and mix for 30 minutes. Suitable flavour was added and mixed for 10 minutes. The final solution was deaerated by applying vacuum for 20-30 minutes. The medicament or fill is ensured for air bubble free and finally cover it and affix the “Status” label.
, Claims:I/We claim,
1. A soft, chewable, orally dissolvable and/or disintegrable capsule comprising: soft capsule outer sheath encapsulating an inner gummy fill material wherein the fill material is in a solid or semi-solid form at room temperature; the soft capsule outer sheath comprising gel-forming polymers, plasticizers, polymer modifiers, hydrophilic fillers and water; and wherein the inner gummy fill material comprising second gel-forming polymers, polymer modifiers, hydrophilic fillers, sweetening agents, stabilizing agents and hydrating materials, wherein the inner fill material comprising one or more biologically active agents.
2. The soft, chewable composition as claimed in claim 1 wherein the biologically active agent is selected from the group consisting of pharmaceuticals, nutritional supplements, vitamins, minerals, fruit extracts, herbals that are intended for local effect in the mouth or the gastro-intestinal tract, or for systemic effect.
3. The soft, chewable composition as claimed in claim 1 wherein the biologically active agent is selected from the group consisting of diagnostics, cosmetics and confectionery products.
4. The soft, chewable composition as claimed in claim 1 wherein the inner gummy fill material in a physical state which is selected from the group consisting of solid, semi-solid and liquid form.
5. The soft, chewable composition as claimed in claim 1 wherein the inner gummy fill material in a physical state which is selected from the group consisting of hydrogel, matrix and hydrocolloid form.
6. The soft, chewable composition as claimed in claim 1 wherein the biologically active ingredient is present in the dissolved or in a dispersed form.
7. The soft, chewable composition as claimed in claim 1 wherein the inner gummy filler material comprising stabilizing agent, sweetening agents and flavouring agents.
8. The soft, chewable composition as claimed in claim 1 wherein the gel-forming polymer selected from the group consisting of gelatin, pectin, carrageenan, gellan gum, locust bean gum, gum arabic, xanthan gum, starch, methylcellulose, agar, konjac, alginates or a combination thereof.
9. The soft, chewable composition as claimed in claim 1 wherein the plasticizer comprises glycerol, sorbitol, maltitol, xylitol or a combination thereof.
10. The soft, chewable composition as claimed in claim 1 wherein the polymer modifier comprises citric acid, lactic acid, tartaric acid, fumaric acid, glycolic acid, or a combination thereof.
11. The soft, chewable composition as claimed in claim 1 wherein the second gel-forming polymer comprises gelatin, partially hydrolyzed gelatin, hydrolyzed gelatin, or a combination thereof.