A stable oral pro-dispersion formulation and implementations thereof

Abstract

The present disclosure provides a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API); (ii) a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent, and a method of preparation thereof. The present disclosure further provides a capsule comprising the pro-dispersion formulation, a method of preparation thereof, and a method of treatment of a condition using the formulation or the capsule.

Description

A STABLE ORAL PRO-DISPERSION FORMULATION AND IMPLEMENTATIONS THEREOFFIELD OF INVENTION

[0001] The present disclosure broadly relates to the field of oral pharmaceutical formulations. The present disclosure particularly relates to a stable pro-dispersion formulation comprising an active pharmaceutical ingredient (API), with enhanced absorption, fast onset of action, and minimal gastrointestinal tract (GIT) side effects. The present disclosure further relates to a capsule comprising the formulation and methods of preparation of the formulation and capsule thereof.BACKGROUND OF THE INVENTION

[0002] The Biopharmaceutical Classification System (BCS) is a critical tool for understanding and predicting the bioavailability of drugs (API). It classifies compounds into four categories (Class 1, 2, 3, and 4) based on their solubility and permeability profiles, which are key factors in determining how well a drug is absorbed in the body after oral administration. BCS Class 1 drugs have high solubility and high permeability, hence are typically well absorbed and have predictable bioavailability. BCS Class 2 drugs with low solubility but high permeability are often absorbed well when they are dissolved, but their poor solubility in aqueous environments, like the gastrointestinal tract, limits their bioavailability. BCS Class 3 drugs with high solubility but low permeability can dissolve well in the body but face difficulties in crossing the biological membranes to reach systemic circulation. BCS Class 4 drugs have both low solubility and low permeability, thus are the most challenging in terms of bioavailability since they struggle both to dissolve in the gastrointestinal tract and to permeate cell membranes.

[0003] In an attempt to enhance the bioavailability of Class 2, 3, and 4 drugs, various drug formulation strategies have been developed. Two of the most common approaches are solubilized systems and lipid -lock technologies. Solubilizedsystems aim to increase the solubility of poorly soluble drugs by formulating with surfactants, cyclodextrins, or other solubilizers that can help dissolve the drug into a more bioavailable form. These systems are typically employed in soft gelatin capsules or liquid formulations, as they can facilitate the drug's dissolution before it reaches the gastrointestinal tract, thus improving absorption. However, other factors, such as drug stability, enzymatic degradation, and gastrointestinal motility, can still impede the drug’s effectiveness. Solubilised systems in the form of selfemulsifying drug delivery systems (SEDDS) have also been proposed, which are defined as isotropic mixtures of one or more hydrophilic solvents, cosolvents and surfactants that are capable of forming fine oil-in-water (O / W) emulsions upon mild agitation and dilution in gastrointestinal fluids; various types of emulsions or suspensions. Various strategies, such as concomitant administration of gastric protectors (as free-drugs or coupled drugs), the use of rectal drug delivery systems, or modified release formulations, have also been investigated to avoid drug-related toxicity in GIT. Lipid-Lock technologies, on the other hand, involve incorporating the drug into a lipid -based formulation, typically in soft-gel capsules. This encapsulation in lipids protects API from the harsh environment of the gastrointestinal tract and facilitates its absorption via the lymphatic system or lipid digestion pathways. While lipid-lock technology can enhance absorption for some drugs, it has limitations as well.

[0004] To improve low solubility and bioavailability, several composition alternatives for administering API were studied; W02007022165 describes an injectable apixaban composition with sulfobutyl ether P-cyclodextrin (SBE-CD) and water. W02008031782 describes a modified release pharmaceutical composition of apixaban comprising plural mini tablets, within a matrix of polymer(s). The mini tablets are suitably filled within a gelatin capsule. EP2442791 and EP3520776 describe apixaban compositions with solid dispersion and many dosage forms of Apixaban (prepared as solubility improved forms). It also includes dispersion compositions whereby apixaban is dispersed in a solvent and co-solvent and finally mixed with digestible oil and surfactants to have homogenous dispersion(s) which can be filled into hard or soft gelatin capsules.

[0005] US4690823A discloses an ibuprofen-containing soft gelatin capsule containing a solution of ibuprofen wherein ibuprofen is dissolved in a polyoxyethylene-polyoxypropylene polymer or in a mixture of a polyalkylene glycol and a surfactant at a temperature of from 45 °C to 65 °C and will remain in solution upon cooling to room temperature. US6221391B1 discloses a clear ibuprofen solution, said solution consisting essentially of a polyoxyethylene derivative of castor oil, polyvinylpyrrolidone, and ibuprofen. US6251426B 1 discloses a liquid soft gel fill formulation consisting essentially of ibuprofen in free acid form in solution; polyethylene glycol; a weight of polyvinylpyrrolidone; and a surfactant. GB2331458B mentions solubilizing systems for difficult pharmaceutical actives by preparing concentrated stable solutions for encapsulation into soft gelatin, wherein a nanoparticle formulation of Ibuprofen having a surface modifier adsorbed on the surface is disclosed. WO2008144888A1 relates to selfemulsifying drug delivery systems (SEDDS), wherein the formulation comprises a therapeutic agent, one or more fatty acid glycerol esters, and one or more polyethylene oxide-containing phospholipids or one or more polyethylene oxide containing fatty acid esters.

[0006] The existing formulations are based on drug solubilization, which increases absorption while decreasing gastrointestinal tract (GIT) side effects, gastrointestinal tract (GIT) side effects were reduced but not eliminated completely. However, the bioavailability may still be affected by factors such as drug crystallization, degradation of the drug in the digestive tract, or insufficient digestion of the lipids, which can impair absorption. Additionally, since lipid digestion is required for absorption, variability in lipid metabolism among patients can lead to inconsistent drug absorption and therapeutic outcomes.

[0007] Therefore, there is a need in the art to develop more advanced drug delivery systems.SUMMARY OF INVENTION

[0008] In an aspect of the present disclosure, there is provided a stable oral prodispersion formulation, comprising: (i) an active pharmaceutical ingredient (API)selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0009] In another aspect of the present disclosure, there is provided a process of preparing the formulation as disclosed herein, the process comprising the steps of: (i) adding one or more SPIM, one or more lipids, one or more solvent with an API and optionally adding at least one pharmaceutically acceptable excipient selected from biodegradable polymer, stabilizers, or combinations thereof, and mixing thoroughly to obtain a clear solution of a first mixture; and (ii) adding one or more surfactants and optionally adding at least one pharmaceutically acceptable excipient selected from biodegradable polymer, stabilizers, or combinations thereof, to the first mixture and processing to form the formulation.

[0010] In another aspect of the present disclosure, there is provided a capsule, comprising the formulation as disclosed herein.

[0011] In another aspect of the present disclosure, there is provided a process of preparing the capsule as disclosed herein, the process comprising filling the formulation as disclosed herein into a shell to obtain the capsule.

[0012] In one another aspect of the present disclosure, there is provided use of the formulation as disclosed herein or the capsule as disclosed herein, for treating or managing a condition.

[0013] In yet another aspect of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, the method comprising treating with the formulation as disclosed herein, or the capsule as disclosed herein.

[0014] These and other features, aspects, and advantages of the present subject matter will be better understood with reference to the following detailed description and appended claims. This summary is provided to introduce a selection of concepts in a simplified form. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS

[0015] The following drawings form a part of the present specification and are included to further illustrate aspects of the present disclosure. The disclosure may be better understood by reference to the drawings in combination with the detailed description of the specific embodiments presented herein.

[0016] Figure 1 depicts a photomicrograph showing API crystals or crystals of API as observed under a microscope for Eg. 11, in accordance with the embodiments herein.

[0017] Figure 2 depicts a photomicrograph showing API crystals as observed under a microscope for Eg. 13, in accordance with the embodiments herein.

[0018] Figure 3 depicts a photomicrograph showing ‘no API crystals’ as observed under a microscope for Eg. 2, in accordance with the embodiments herein.

[0019] Figure 4 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 19, in accordance with the embodiments herein.

[0020] Figure 5 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 20, in accordance with the embodiments herein.

[0021] Figure 6 depicts a photomicrograph showing ‘no API crystals’ as observed under a microscope for Eg. 9, in accordance with the embodiments herein.

[0022] Figure 7 is a graphical representation showing the effect of SPIM concentration in the formulations on zeta potential, in accordance with the embodiments herein.

[0023] Figure 8 depicts a photograph showing ‘precipitation’ as observed for Eg. 31, in accordance with the embodiments herein.

[0024] Figure 9 depicts a photograph showing ‘phase separation and precipitation’ as observed for Eg. 40, in accordance with the embodiments herein.

[0025] Figure 10 depicts a photograph showing ‘Precipitation and API crystals’ as observed for Eg. 39, in accordance with the embodiments herein.

[0026] Figure 11 depicts a photograph showing ‘sedimentation of precipitate’ as observed for Eg. 30, in accordance with the embodiments herein.

[0027] Figure 12 depicts a photograph showing ‘no API crystals or no precipitation or no sedimentation or phase separation’ as observed for Eg. 24, in accordance with the embodiments herein.

[0028] Figure 13 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 36, in accordance with the embodiments herein.

[0029] Figure 14 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 37, in accordance with the embodiments herein.

[0030] Figure 15 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 38, in accordance with the embodiments herein.

[0031] Figure 16 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 39, in accordance with the embodiments herein.

[0032] Figure 17 depicts a photomicrograph showing ‘no API crystals’ as observed under a microscope for Eg. 24, in accordance with the embodiments herein.

[0033] Figure 18 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 47, in accordance with the embodiments herein.

[0034] Figure 19 depicts a photomicrograph showing ‘aggregated large particles and precipitation’ as observed under a microscope for Eg. 46, in accordance with the embodiments herein.

[0035] Figure 20 depicts a photomicrograph showing ‘no API crystals’ as observed under a microscope for Eg. 41, in accordance with the embodiments herein.

[0036] Figure 21 depicts a photomicrograph showing ‘API crystals’ as observed under a microscope for Eg. 67, in accordance with the embodiments herein.

[0037] Figure 22 depicts a photomicrograph showing ‘no API crystals’ as observed under a microscope for Eg. 63, in accordance with the embodiments herein.

[0038] Figure 23 depicts photomicrographs showing examined lesions or ulcers at 10X magnification using binocular microscope, [A] Excised gastric mucosa of rats treated with Ibuprofen-comprising formulation (Eg. 2): Group- 1; [B] Excised gastric mucosa of rats treated with normal saline (control): Group-2, in accordance with the embodiments herein.

[0039] Figure 24 depicts [A] transmission electron microscopy (TEM) images of formed nanoparticles when ibuprofen pro-dispersion formulation (Eg. 2) ishydrated with purified water; and [B] TEM image of formed nanoparticles when dextromethorphan pro-dispersion formulation (Eg. 26) is hydrated with purified water, in accordance with the embodiments herein.DETAILED DESCRIPTION OF THE INVENTION

[0040] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions, and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any or more of such steps or features. Definitions

[0041] For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are delineated here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.

[0042] The articles “a”, “an” and “the” are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article.

[0043] The terms “comprise” and “comprising” are used in the inclusive, open sense, meaning that additional elements may be included. It is not intended to be construed as “consists of only”.

[0044] Throughout this specification, unless the context requires otherwise the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated element or step or group of elements or steps but not the exclusion of any other element or step or group of elements or steps.

[0045] The term “including” is used to mean “including but not limited to”. “Including” and “including but not limited to” are used interchangeably.

[0046] The term “w / w,” as used herein, refers to percentage by weight, relative to the weight of the total composition, unless otherwise specified.

[0047] The term “ICH” refers to International Council for Harmonisation, which provides guidelines for stability testing of pharmaceutical products to ensure that they maintain their intended quality, efficacy, and safety throughout their shelf-life. The ICH defines the following storage conditions for stability studies: Long-Term Stability Testing: Temperature: 25°C ± 2°C (room temperature), Relative Humidity: 60% ± 5% RH (relative humidity), Duration: 12-24 months (typically for a new drug product, although longer durations may be required in some cases depending on regulatory requirements). Accelerated Stability Testing: Temperature: 40°C ± 2°C (higher than room temperature), Relative Humidity: 75% ± 5% RH (high humidity), Duration: 6 months. This is typically used to predict long-term stability and to quickly assess how the product performs under stress conditions.

[0048] The term “pro-dispersion formulation” or “PDF” as used herein refers to a system designed to optimize the dispersion of an active pharmaceutical ingredient (API) in a medium, typically to enhance the solubility, stability, and bioavailability of the drug. The pro-dispersion formulation when in contact with simulated conditions or suitable environment for example gastrointestinal environment or GIT fluids or at a particular pH of gastrointestinal tract (GIT), instantly converts into drug carrier particles and the formulation acts as a carrier system of API / drug. The pro-dispersion formulation of the present disclosure, in particular, is designed for oral administration / sublingual administration and provides sustained / extended release, enhanced solubility, stability and thus the bioavailability of the desired API.

[0049] The term “active pharmaceutical ingredient” or “API” as used herein refers to the biologically active component of a pharmaceutical drug that is responsible for the therapeutic effects. The terms “active pharmaceutical ingredient”, “API” “drug” are used interchangeably. For the purpose of the present disclosure, API is selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof. API could be in the form of salts, solvates, or polymorphs thereof. Ingeneral, derivatives of a compound refer to compounds derived from the parent compound that are chemically similar and do not show any alteration in their properties. The derivatives of API include chemically similar compounds derived from API or having the same core structure of API without alteration in their chemical / physical / biological / pharmacological properties.

[0050] The term “NSAIDs” or “Non-Steroidal Anti-Inflammatory Drugs" refers to a class of medications used to reduce pain, inflammation, and fever by inhibiting enzymes (COX-1 and COX-2) involved in prostaglandin production.

[0051] The term “antitussives" refers to medications used to suppress or relieve coughing, by acting on the cough reflex in the brain or by soothing the throat.

[0052] The term “analgesics" refers to a type of medication used to relieve pain or manages pain.

[0053] The term "factor Xa inhibitors" refers to a class of anticoagulant medications that work by inhibiting the activity of Factor Xa, an enzyme involved in blood clotting.

[0054] The term "vitamins” refers to essential compounds required in small amounts for normal body function, growth, and health, which help regulate various biochemical processes and are obtained primarily through diet.

[0055] The term "other drugs” refers to APIs that do not fall under above mentioned definitions.

[0056] The term “specialised polymeric interfacial modifier” or SPIM” as used herein refers to a substance that is specifically designed to modify or influence the interfacial properties between two phases such as between a solid and liquid, two immiscible liquids, or a liquid and gas in a formulation. The SPIM as used herein also includes P-glycoprotein inhibitors. The term P-glycoprotein inhibitors or specialized interfacial modifiers as used herein generally include agent(s) that facilitate the conversion of pro-dispersion formulation into drug entrapped carrier particles instantaneously, also imparts suitable surface characteristics on carrier particles which in turn helps in the stabilization of these particles and improvement of absorption of these particles at the absorption site thereby enhancing absorption of the API. The term "Specialized Polymeric Interfacial Modifiers" (SPIMs) refersto one or more excipients that help in the spontaneous formation of carrier particles in-situ in the GIT (gastrointestinal tract), the protection of the payload active pharmaceutical ingredient (API) in harsh biological fluids, the sustained / extended release of entrapped API, and improved bioavailability. Examples of SPIM include but not limited to poloxamers, polyvinyl compounds, polyvinylpyrrolidones or its derivatives, polyethylene glycol derivatives having molecular weight greater than 350 g / mol, phospholipids, polyoxyethylene fatty acid esters, sucrose esters, phosphatidylcholines or its derivatives thereof, tocopherol esters, D-a-tocopheryl polyethylene glycol succinate (TPGS) or derivatives thereof, ascorbic acid esters, pegylated compounds, pegylated lipids, or combinations thereof. Poloxamers are block copolymers of poly(ethylene oxide) (PEG) and poly(propylene oxide) (PPO) having an amphiphilic character. Examples of poloxamers of varied chain length include but are not limited to poloxamer 188, and poloxamer 407. Polyethylene glycol or PEG refers to polyethylene oxide compounds having varying molecular weight which may be optionally substituted. Examples of polyethylene glycol derivatives having molecular weight greater than 350 g / mol include but are not limited to, PEG 600, Methoxy Polyethylene glycol 2000, and PEG 2000. Examples of polyethylene glycol (PEG) derivatives having molecular weight lesser than 350 g / mol include but are not limited to, PEG 200, and PEG 300. Polyoxyethylene fatty acid esters refer to polyoxyethylene esters of fatty acids obtained by esterification of fatty acids with polyoxyethylene. Examples of ascorbic acid esters include but are not limited to ascorbyl palmitate. Examples of sucrose esters include but are not limited to sugar ester D-1216, sucrose acetate isobutyrate, and sucrose palmitate. Example of phosphatidylcholines and phospholipids or its derivatives thereof includes but is not limited to lecithin. Example of pegylated compounds includes but is not limited to PEG 32 stearate.

[0057] The term “lipids” as used herein refers to organic compounds that are hydrophobic or amphiphilic and are insoluble in water. For the purpose of the present disclosure, lipids used in the present invention include fats, cholesterol, long chain triglycerides, medium-chain triglycerides, fatty acids, fatty alcohols, fatty acid esters of glycerol, glyceryl stearate, oils, propylene glycol laurate, orcombinations thereof. The term “oils” as used herein refers to edible oils, examples of which include but are not limited to soybean oil, castor oil, DHA (Docosahexaenoic acid) oil, EPA (Eicosapentaenoic acid) oil, sesame oil, cottonseed oil, olive oil, and coconut oil. The term “triglycerides” refers to ester derived from three fatty acids and glycerol. The term “long-chain triglycerides” refers to ester derived from three fatty acids comprising more than 16 carbon atoms with glycerol. The term “medium-chain triglycerides” refers to ester derived from three fatty acids comprising less than 16 carbon atoms with glycerol. The term “fatty acid esters of glycerol” refers to esters derived from fatty acid and glycerol, examples include glyceryl dibehenate, glyceryl monolinoleate, glyceryl monosterate, and glyceryl distearate. The term “fats” refers to or triglycerides, esters of fatty acids or their mixtures and include but not limited to hard fats or soft fats.

[0058] The term “fatty acid” as used herein refers to compounds of varied carbon chain length, comprising a carboxylic acid group linked to a hydrocarbon, wherein the hydrocarbon could be substituted or unsubstituted aliphatic, aromatic groups. In particular, fatty acids refer to substituted or unsubstituted, saturated or unsaturated, straight chain or branched aliphatic hydrocarbon with at least one carboxylic acid group. Examples of fatty acids include but not limited to stearic acid, and oleic acid.

[0059] The term “fatty alcohol” as used herein refers to compounds of varied long carbon chain length, comprising a hydroxyl group with a hydrocarbon, wherein the hydrocarbon could be substituted or unsubstituted, saturated or unsaturated, straight chain or branched, aliphatic group comprising more than 10 carbon atoms. Examples of fatty alcohols include but not limited to myristic alcohol, cetyl alcohol, stearyl alcohol, and cetostearyl alcohol.

[0060] The term “surfactant” as used herein are amphiphilic molecules and are thus absorbed in the interface. At the interface, they align themselves such that they reduce the surface or interfacial tension. Surfactants contemplated in the present invention include but are not limited to anionic surfactants, amphoteric surfactants, non-ionic surfactants, and macromolecular surfactants. The surfactants are selectedfrom fatty acid esters of sorbitan (polyol esters / span series), polyoxyl hydrogenated castor oil, polyoxyethylene esters, polysorbates, fatty acid esters, polyglycerol esters, propylene glycol fatty acid esters, sulfate -based surfactants, sulfonate-based surfactants, or combinations thereof. Examples of fatty acid esters of sorbitan include but not limited to polyol esters and span series compounds. Examples of polysorbates include but not limited to polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, and polysorbate 85. Examples of polyoxyl hydrogenated castor oil include but not limited to polyoxyl 40 hydrogenated castor oil, and polyoxyl 35 hydrogenated castor oil.

[0061] The term "solvent" means a solvent or solvent system wherein a substantial portion of an active drug may be solubilized therein.

[0062] The term “alcohols” as used herein refers to primary alcohols, the organic compounds that carry at least one hydroxyl (-OH) functional group bound to a saturated carbon atom having not more than 10 carbon atoms and are useful as solvent in the formulation.

[0063] As used herein in the specifications, the term "Pro -formulation or Prodispersion system” also refers to “Inversol technology”, "Pro-nano emulsion system", lipid nanodispersion," "nanoemulsion / lipid-polymer nanoemulsion”, “lipidic / polymeric nanoparticulate dispersion," "lipid-polymer hybrid nanodispersion," “colloidal dispersion / system”, “pro-colloidal system,” “Dispersion,” “Liquid,” “Concentrate,” “Gel,” and "self-emulsifying system". The term "self-emulsifying system" herein also includes a self-nano emulsifying system.

[0064] " Pharmaceutical composition" and "composition" and "formulation" as used herein are equivalent terms referring to a composition of active ingredients for pharmaceutical use.

[0065] As used herein, the term “in-situ” refers to simulated gastrointestinal tract (GIT) pH conditions (pH from 1.2 to 7.4) i.e. 0.1N HC1, 6.2 pH buffer and 7.4 pH buffer.

[0066] As used herein, the term "pharmaceutically acceptable" refers to those compounds, materials, compositions, and / or dosage forms that are, within the scopeof sound medical judgment, regarded as safe for consumption, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit-risk ratio. Several pharmaceutically acceptable ingredients are known in the art and in official publications; for example, Inactive Ingredient database and the United States Pharmacopeia describe the analytical criteria to assess the pharmaceutical acceptability of numerous ingredients of interest.

[0067] As used herein, the terms "preferred" and "preferably" refer to embodiments of the invention that may afford certain benefits under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the invention.

[0068] Ratios, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited.

[0069] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described. All publications mentioned herein are incorporated herein by reference.

[0070] As discussed in the background, many Class 2, 3, and 4 drugs (API) are prone to degradation under acidic conditions in the stomach or due to enzymatic activity in the gastrointestinal tract. In soft-gel formulations, the drug may degrade before reaching its target site, reducing the therapeutic effectiveness. Further, poorly soluble drugs tend to crystallize when exposed to the gastrointestinal tract, which can drastically reduce the amount of drug available for absorption becauseonly the dissolved form of a drug can be absorbed across the intestinal wall. For lipid-lock technologies, since the absorption of the drug is dependent on lipid digestion, the effectiveness of these formulations can vary based on an individual’s dietary habits or digestive health, and absorption might be suboptimal in patients with impaired lipid metabolism.

[0071] Accordingly, the present invention provides a pro-dispersion formulation (PDF) designed to be stable yet has the capability to undergo a transformation upon reaching the gastrointestinal tract (GIT), where the environment (including fluids, pH and other GI conditions) triggers the conversion of the system into carrier particles. The formulation is filled inside a capsule, made from various materials such as softgel, hardgel, or other suitable capsule shell materials. These capsules are designed to provide sustained / controlled release and protect the active ingredient during transit through the gastrointestinal (GI) tract. Upon ingestion, the capsule dissolves when in contact with GIT fluids, the acidic and enzymatic conditions of the GIT. This dissolution releases the pro-dispersion formulation, which undergoes a spontaneous conversion into carrier particles in GIT fluids, triggered by the specific pH conditions and other environmental factors found in the GIT. The resulting system offers several advantages, such as enhanced stability, solubility, bioavailability, and sustained release. It also helps in protecting the drug from potential degradation due to the harsh conditions in the gastrointestinal tract. Further, the drug system does not crystallize when exposed to the gastrointestinal tract, thus retaining the amount of drug available for absorption. The drug-loaded particles formed in the GIT remain stable for up to 6 hours.

[0072] Embodiments herein provide a stable oral pro-dispersion formulation comprising (i) an active pharmaceutical ingredient (API); (ii) a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent. The formulation optionally comprises a pharmaceutically acceptable excipient selected from biodegradable polymers, stabilizers, or combinations thereof. Embodiments of the present invention also provide a capsule comprising the formulation and method of preparing the formulation and capsule thereof.

[0073] Embodiments herein further provide use of the formulation or the capsule; and a method of treating or managing a condition comprising administering the formulation or the capsule to a subject in need thereof.

[0074] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API); (ii) a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0075] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0076] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent.

[0077] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation comprises a pharmaceutically acceptable excipient selected from biodegradable polymers, stabilizers, or combinations thereof.

[0078] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; (v) a solvent and (vi) a pharmaceuticallyacceptable excipient selected from biodegradable polymers, stabilizers, or combinations thereof.

[0079] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; (v) a solvent and (vi) a stabilizer.

[0080] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; (v) 5 to 80% by weight of a solvent; and (vi) 0.01 to 2% by weight of a stabilizer.

[0081] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; (v) a solvent; (vi) a stabilizer; and (vii) a biodegradable polymer.

[0082] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation is substantially free of water and has a moisture content not more than 5% by weight.

[0083] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation has a shelflife in a range of 18 to 24 months at ICH conditions. In another embodiment of the present disclosure, wherein the formulation is physically and chemically shelfstable for at least two years.

[0084] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation shows no ulcerogenic potential.

[0085] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation is in the form of a nano-dispersion, nano-emulsion, dispersion, emulsion, solubilized liquid, liquid, gel, concentrate, colloidal dispersion, liquid adsorbed onto a substrate, or nanoparticles. In another embodiment of the present disclosure, wherein the formulation is the form of a colloidal dispersion, nano-dispersion, or nanoemulsion.

[0086] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, or their derivatives, or combinations thereof.

[0087] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the active pharmaceutical ingredient is present in a weight range of 1 to 30% by weight, with respect to the formulation.

[0088] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is selected from ibuprofen, naproxen, mefenamic acid, piroxicam, meloxicam, tenoxicam, aspirin, diclofenac, aceclofenac, etodolac, indomethacin, sulindac, ketoprofen, etoricoxib, celecoxib, dextromethorphan, benzonatate, pentoxyverine, methadone, normethadone, levodropropizine, tapentadol, codeine, fentanyl, hydrocodone, meperidine, naloxone or naltrexone, oxycodone, morphine, apixaban, rivaroxaban, edoxaban, betrixaban, fondaparinux, idraparinux, otamixaban, letaxaban, darexaban, antithrombin alfa, vitamins, vitamin D or D3, telmisartan, azilsartan, candesartan, irbesartan, olmesartan, valsartan, losartan, eprosartan, axitinib, dasatinib, erlotinib, imatinib, nilotinib, pazopanib, sunitinib, gefitinib, sorafenib, nintedanib, capecitabine, cladribine, fludarabine, 5-fluorouracil, gemcitabine, cytarabine, pemetrexed, methotrexate, pralatrexate, floxuridine, decitabine,clofarabine, nelarabine, simvastatin, lovastatin, atorvastatin, pitavastatin, pravastatin, fluvastatin, rosuvastatin, cerivastatin, cyclosporine, everolimus, tacrolimus, sirolimus, mycophenolate mofetil, progesterone, testosterone, levothyroxine, estradiol, danazol, fexofenadine, loratadine, domperidone, ondansetron, palonosetron, aprepitant, netupitant, gabapentin, pregabalin, mirogabalin, baclofen, other GABA derivatives, hormones, their derivatives, their salts, solvates, or combinations thereof. In another embodiment of the present disclosure, GABA derivatives include derivative of the neurotransmitter gamma- aminobutyric acid (GABA); and hormones include organic compounds act as chemical messenger, and are chemically peptides, steroids, amino acid derivatives or fatty acid derivatives.

[0089] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is a NS AID, selected from ibuprofen, naproxen, mefenamic acid, piroxicam, meloxicam, tenoxicam, aspirin, diclofenac, aceclofenac, etodolac, indomethacin, sulindac, ketoprofen, etoricoxib, celecoxib, or their derivatives, or combinations thereof. In another embodiment of the present disclosure, the API is a NSAID, preferably ibuprofen.

[0090] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API), wherein the API is a NSAID, preferably ibuprofen; (ii) a specialised polymeric interfacial modifier (SPIM), preferably; (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0091] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API), wherein the API is a NSAID, preferably ibuprofen, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0092] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 10 to 30% by weight of an active pharmaceutical ingredient (API), wherein the API is a NSAID, preferablyibuprofen, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0093] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 10 to 30% by weight of an active pharmaceutical ingredient (API), wherein the API is a NSAID, preferably ibuprofen, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent.

[0094] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 10 to 30% by weight of an active pharmaceutical ingredient (API), wherein the API is a NSAID, preferably ibuprofen, its derivatives, salts or solvates thereof; (ii) 0.4 to 27% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 10 to 45% by weight of a lipid; (iv) 15 to 55% by weight of a surfactant; and (v) 5 to 30% by weight of a solvent.

[0095] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is an antitussive, selected from dextromethorphan, benzonatate, pentoxyverine, methadone, normethadone, levodropropizine, or their derivatives, or combinations thereof. In another embodiment of the present disclosure, the API is an antitussive, preferably dextromethorphan .

[0096] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API), wherein the API is an antitussive, preferably dextromethorphan, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0097] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 10% by weight of an activepharmaceutical ingredient (API), wherein the API is an antitussive, preferably dextromethorphan, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0098] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 10% by weight of an active pharmaceutical ingredient (API), wherein the API is an antitussive, preferably dextromethorphan, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent.

[0099] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 10% by weight of an active pharmaceutical ingredient (API), wherein the API is an antitussive, preferably dextromethorphan, its derivatives, salts or solvates thereof; (ii) 0.1 to 10% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 5 to 60% by weight of a lipid; (iv) 15 to 58% by weight of a surfactant; and (v) 14 to 60% by weight of a solvent.

[0100] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is an analgesic, selected from tapentadol, codeine, fentanyl, hydrocodone, meperidine, naloxone or naltrexone, oxycodone, morphine, or their derivatives, or combinations thereof. In another embodiment of the present disclosure, the API is an analgesic, preferably tapentadol.

[0101] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API), wherein the API is an analgesic, preferably tapentadol, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0102] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 10 % by weight of an activepharmaceutical ingredient (API), wherein the API is an analgesic, preferably tapentadol, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0103] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 10 % by weight of an active pharmaceutical ingredient (API), wherein the API is an analgesic, preferably tapentadol, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent.

[0104] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 10 % by weight of an active pharmaceutical ingredient (API), wherein the API is an analgesic, preferably tapentadol, its derivatives, salts or solvates thereof; (ii) 0.5 to 15% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 10 to 58% by weight of a lipid; (iv) 10 to 55% by weight of a surfactant; and (v) 12 to 63% by weight of a solvent.

[0105] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is a factor Xa inhibitor, selected from apixaban, rivaroxaban, edoxaban, betrixaban, fondaparinux, idraparinux, otamixaban, letaxaban, darexaban, antithrombin alfa, or their derivatives, or combinations thereof. In another embodiment of the present disclosure, the API is a factor Xa inhibitor, preferably apixaban.

[0106] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API), wherein the API is a factor Xa inhibitor, preferably apixaban, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0107] In an embodiment of the present disclosure, there is provided stable oral a formulation, comprising (i) 1 to 8% by weight of an active pharmaceuticalingredient (API), wherein the API is a factor Xa inhibitor, preferably apixaban, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0108] In an embodiment of the present disclosure, there is provided stable oral a formulation, comprising (i) 1 to 8% by weight of an active pharmaceutical ingredient (API), wherein the API is a factor Xa inhibitor, preferably apixaban, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent.

[0109] In an embodiment of the present disclosure, there is provided stable oral a formulation, comprising (i) 1 to 8% by weight of an active pharmaceutical ingredient (API), wherein the API is a factor Xa inhibitor, preferably apixaban, its derivatives, salts or solvates thereof; (ii) 1 to 10% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 5 to 30% by weight of a lipid; (iv) 5 to 36% by weight of a surfactant; and (v) 50 to 80% by weight of a solvent.

[0110] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is vitamin, preferably vitamin D and D3.

[0111] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API), wherein the API is a vitamin, preferably vitamin D3, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0112] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 1 to 10% by weight of an active pharmaceutical ingredient (API), wherein the API is a vitamin, preferably vitamin D3, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0113] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 1 to 10% by weight of an active pharmaceutical ingredient (API), wherein the API is a vitamin, preferably vitamin D3, its derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent.

[0114] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 1 to 10% by weight of an active pharmaceutical ingredient (API), wherein the API is a vitamin, preferably vitamin D3, its derivatives, salts or solvates thereof; (ii) 1 to 7% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 10 to 58% by weight of a surfactant; and (v) 10 to 40% by weight of a solvent.

[0115] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API is other drug selected from telmisartan, azilsartan, candesartan, irbesartan, olmesartan, valsartan, losartan, eprosartan, axitinib, dasatinib, erlotinib, imatinib, nilotinib, pazopanib, sunitinib, gefitinib, sorafenib, nintedanib, capecitabine, cladribine, fludarabine, 5- fluorouracil, gemcitabine, cytarabine, pemetrexed, methotrexate, pralatrexate, floxuridine, decitabine, clofarabine, nelarabine, simvastatin, lovastatin, atorvastatin, pitavastatin, pravastatin, fluvastatin, rosuvastatin, cerivastatin, cyclosporine, everolimus, tacrolimus, sirolimus, mycophenolate mofetil, progesterone, testosterone, levothyroxine, estradiol, danazol, fexofenadine, loratadine, domperidone, ondansetron, palonosetron, aprepitant, netupitant, gabapentin, pregabalin, mirogabalin, baclofen, other GABA derivatives, hormones, or their derivatives, or combinations thereof.

[0116] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) an active pharmaceutical ingredient (API), wherein the API is other drug, preferably selected from atorvastatin, Rosuvastatin, aspirin, diclofenac, their derivatives, salts or solvates thereof; (ii) 0.1to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0117] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 25% by weight of an active pharmaceutical ingredient (API), wherein the API is other drug, preferably selected from atorvastatin, rosuvastatin, aspirin, diclofenac, their derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent.

[0118] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 25% by weight of an active pharmaceutical ingredient (API), wherein the API is other drug, preferably selected from atorvastatin, rosuvastatin, aspirin, diclofenac, their derivatives, salts or solvates thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent.

[0119] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising (i) 2 to 25% by weight of an active pharmaceutical ingredient (API), wherein the API is other drug, preferably selected from atorvastatin, rosuvastatin, aspirin, diclofenac, their derivatives, salts or solvates thereof; (ii) 1 to 12% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 5 to 45% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 35% by weight of a solvent.

[0120] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the SPIM is selected from poloxamers, polyvinyl compounds, polyvinylpyrrolidones or its derivatives, polyethylene glycol derivatives having molecular weight greater than 350 g / mol, phospholipids, polyoxyethylene fatty acid esters, sucrose esters, phosphatidylcholines or its derivatives thereof, tocopherol esters, D-a-tocopheryl polyethylene glycol succinate (TPGS) or derivatives thereof, ascorbic acid esters, pegylated compounds, pegylated lipids, or combinations thereof.

[0121] In an embodiment of the present disclosure, there is provided a stable oral formulation as disclosed herein, wherein the API and the SPIM are in a weight ratio range of 1:0.02 to 1:4.6. In another embodiment of the present disclosure, wherein the API and the SPIM are in a weight ratio range of 1:0.02 to 1:1.8; and the API is NSAID preferably ibuprofen. In another embodiment of the present disclosure, wherein the API and the SPIM are in a weight ratio range of 1:0.05 to 1:1.7; and the API is antitussive preferably dextromethorphan. In another embodiment of the present disclosure, wherein the API and the SPIM are in a weight ratio range of 1:0.2 to 1:1.8; and the API is analgesic, preferably tapentadol. In another embodiment of the present disclosure, wherein the API and the SPIM are in a weight ratio range of 1:0.3 to 1:1.5; and the API is vitamin, preferably vitamin D3. In another embodiment of the present disclosure, wherein the API and the SPIM are in a weight ratio range of 1:0.1 to 1:2.6; and the API is factor Xa inhibitor, preferably apixaban. In another embodiment of the present disclosure, wherein the API and the SPIM are in a weight ratio range of 1 :0.02 to 1:4.6; and the API is other drug, preferably selected from atorvastatin, rosuvastatin, aspirin and diclofenac.

[0122] In an embodiment of the present disclosure, there is provided a stable oral formulation as disclosed herein, wherein the lipid is selected from fats, cholesterol, long chain triglycerides, medium-chain triglycerides, fatty acids, fatty alcohols, fatty acid esters of glycerol, glyceryl stearate, oils, propylene glycol laurate, or combinations thereof.

[0123] In an embodiment of the present disclosure, there is provided a prodispersion formulation as disclosed herein, wherein the lipid is present in a weight range of 4 to 62% by weight, with respect to the formulation.

[0124] In an embodiment of the present disclosure, there is provided a prodispersion formulation, wherein the formulation comprises 4 to 62% by weight a lipid selected from fats, cholesterol, long chain triglycerides, medium-chain triglycerides, fatty acids, fatty alcohols, fatty acid esters of glycerol, glyceryl stearate, oils, propylene glycol laurate, or combinations thereof.

[0125] In an embodiment of the present disclosure, there is provided a stable oral formulation as disclosed herein, wherein the API and the lipid are in a weight ratiorange of 1:0.4 to 1: 30.8. In another embodiment of the present disclosure, wherein the API and the lipid are in a weight ratio range of 1:0.4 to 1:2; and the API is NSAID preferably ibuprofen. In another embodiment of the present disclosure, wherein the API and the lipid are in a weight ratio range of 1:0.5 to 1: 17; and the API is antitussive preferably dextromethorphan. In another embodiment of the present disclosure, wherein the API and the lipid are in a weight ratio range of 1:1 to 1:21; and the API is analgesic, preferably tapentadol. In another embodiment of the present disclosure, wherein the API and the lipid are in a weight ratio range of 1:0.4 to 1:30.8; and the API is vitamin, preferably vitamin D3. In another embodiment of the present disclosure, wherein the API and the lipid are in a weight ratio range of 1:0.5 to 1:10; and the API is factor Xa inhibitor, preferably apixaban. In another embodiment of the present disclosure, wherein the API and the lipid are in a weight ratio range of 1:0.4 to 1:30.8; and the API is other drug, preferably selected from atorvastatin, rosuvastatin, aspirin and diclofenac.

[0126] In an embodiment of the present disclosure, there is provided a stable oral formulation as disclosed herein, wherein the surfactant is selected fatty acid esters of sorbitan, polyoxyl hydrogenated castor oil, polyoxyethylene esters / polysorbates, fatty acid esters, polyglycerol esters, propylene glycol fatty acid esters, sulfate- based surfactants, sulfonate -based surfactants, or combinations thereof.

[0127] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the surfactant is present in a weight range of 5 to 58% by weight, with respect to the formulation.

[0128] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation comprises 5 to 58% by weight of a surfactant selected from fatty acid esters of sorbitan, polyoxyl hydrogenated castor oil, polyoxyethylene esters / polysorbates, fatty acid esters, polyglycerol esters, propylene glycol fatty acid esters, sulfate-based surfactants, sulfonate-based surfactants, or combinations thereof.

[0129] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API and the surfactant are in the weight ratio range of 1:0.5 to 1:27.5. In another embodiment of the presentdisclosure, wherein the API and the surfactant are in a weight ratio range of 1:0.5 to 1:6; and the API is NS AID preferably ibuprofen. In another embodiment of the present disclosure, wherein the API and the surfactant are in a weight ratio range of 1:1 to 1:23; and the API is antitussive preferably dextromethorphan. In another embodiment of the present disclosure, wherein the API and the surfactant are in a weight ratio range of 1:1 to 1: 17; and the API is analgesic, preferably tapentadol. In another embodiment of the present disclosure, wherein the API and the surfactant are in a weight ratio range of 1: 1 to 1:27.5; and the API is vitamin, preferably vitamin D3. In another embodiment of the present disclosure, wherein the API and the surfactant are in a weight ratio range of 1:0.5 to 1:21; and the API is factor Xa inhibitor, preferably apixaban. In another embodiment of the present disclosure, wherein the API and the surfactant are in a weight ratio range of 1:0.5 to 1:27.5; and the API is other drug, preferably selected from atorvastatin, rosuvastatin, aspirin and diclofenac.

[0130] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the solvent is selected from alcohols, benzyl alcohol, ethanol, propylene glycol, polyethylene glycols having molecular weight less than 350 g / mol (PEG 200, PEG 300), propyl ethylene glycol ethers, propylene glycol esters, caprylocaproyl macrogolglycerides or combinations thereof.

[0131] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the solvent is present in a weight range of 5 to 80% by weight, with respect to the formulation.

[0132] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation comprises 5 to 80% by weight of a solvent selected from alcohols, benzyl alcohol, ethanol, propylene glycol, polyethylene glycols having molecular weight less than 350 g / mol (PEG 200, PEG 300), propyl ethylene glycol ethers, propylene glycol esters, caprylocaproyl macrogolglycerides or combinations thereof.

[0133] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the API and the solvent arein a weight ratio range of 1:0.2 to 1:34.1. In another embodiment of the present disclosure, wherein the API and the solvent are in a weight ratio range of 1:0.2 to 1:1; and the API is NS AID preferably ibuprofen. In another embodiment of the present disclosure, wherein the API and the solvent are in a weight ratio range of 1:2 to 1:14; and the API is antitussive preferably dextromethorphan. In another embodiment of the present disclosure, wherein the API and the solvent are in a weight ratio range of 1:3 to 1:8; and the API is analgesic, preferably tapentadol. In another embodiment of the present disclosure, wherein the API and the solvent are in a weight ratio range of 1:3 to 1:17; and the API is vitamin, preferably vitamin D3. In another embodiment of the present disclosure, wherein the API and the solvent are in a weight ratio range of 1:10 to 1:34.1; and the API is factor Xa inhibitor, preferably apixaban. In another embodiment of the present disclosure, wherein the API and the solvent are in a weight ratio range of 1:0.2 to 1:34.1; and the API is other drug, preferably selected from atorvastatin, rosuvastatin, aspirin and diclofenac.

[0134] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the formulation comprises a pharmaceutically acceptable excipient selected from biodegradable polymers, stabilizers, or combinations thereof.

[0135] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the biodegradable polymer is selected from polyvinyl alcohol, polylysines, polyglycines, cellulose or derivatives thereof, polyethylene-based polymers, hyaluronate or derivatives thereof, natural gums, or combinations thereof.

[0136] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the stabilizer is selected from sodium bisulfite, butylated hydroxy toluene (BHT), butylated hydroxy anisole (BHA), sodium / potassium metabisulfite, tocopherols, uric acid, lipoic acid, ascorbic acid, tert-Butylhydroquinone (TBHQ), propyl gallate, or combinations thereof.

[0137] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation as disclosed herein, wherein the stabilizer is in the weight range of 0.05 to 2% by weight, with respect to the formulation.

[0138] In an embodiment of the present disclosure, there is provided a prodispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent, with a proviso that if API is NSAID preferably ibuprofen, in a weight range of 10 to 30% (w / w), then the SPIM is in a weight range of 0.4 to 27%(w / w), the lipid is in a weight range of 10 to 45% (w / w), the surfactant is in a weight range of 15 to 55%(w / w), the solvent is in weight range of 5 to 30%(w / w), with respect to the formulation.

[0139] In an embodiment of the present disclosure, there is provided a prodispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent, with a proviso that if API is NSAID preferably ibuprofen, in a weight range of 10 to 30% (w / w), then the SPIM is in a weight range of 0.4 to 27%(w / w), the lipid is in a weight range of 10 to 45%(w / w), the surfactant is in a weight range of 15 to 55%(w / w), the solvent is in weight range of 5 to 30%(w / w), with respect to the formulation.

[0140] In an embodiment of the present disclosure, there is provided a prodispersion formulation, comprising: (i) 10 to 30% by weight of an NSAID, preferably ibuprofen; (ii) 0.4 to 27% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 10 to 45% by weight of a lipid; (iv) 15 to 55% by weight of a surfactant; and (v) 5 to 30% by weight of a solvent, wherein the API and the solvent are in a weight ratio range of 1:0.2 to 1:1; the API and the lipid arein a weight ratio range of 1:0.4 to 1:2; the API and the surfactant are in a weight ratio range of 1:0.5 to 1:6; and the API and the SPIM are in a weight ratio range of 1:0.02 to 1:1.8.

[0141] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 20 to 22% by weight of a NSAID, preferably ibuprofen; (ii) 10 to 17% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 25 to 29% by weight of a lipid; (iv) 33 to 35% by weight of a surfactant; and (v) 5 to 10% by weight of a solvent.

[0142] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent, with a proviso that if API is antitussive preferably dextromethorphan, in a weight range of 2 to 10%(w / w), then the SPIM is in a weight range of 0.1 to 10%(w / w), the lipid is in a weight range of 5 to 60%(w / w), the surfactant is in a weight range of 15 to 58%(w / w), the solvent is in weight range of 14 to 60%(w / w), with respect to the formulation.

[0143] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent, with a proviso that if API is antitussive preferably dextromethorphan, in a weight range of 2 to 10%(w / w), then the SPIM is in a weight range of 0.1 to 10%(w / w), the lipid is in a weight range of 5 to 60%(w / w), the surfactant is in a weight range of 15 to 58%(w / w), the solvent is in weight range of 14 to 60%(w / w), with respect to the formulation.

[0144] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 2 to 10% by weight of an antitussive, preferably dextromethorphan; (ii) 0.1 to 10% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 5 to 60% by weight of a lipid; (iv) 15 to 58% by weight of a surfactant; and (v) 14 to 60% by weight of a solvent, wherein the API and the solvent are in a weight ratio range of 1 :2 to 1:14; the API and the surfactant are in a weight ratio range of 1 : 1 to 1:23; the API and the lipid are in a weight ratio range of 1:0.5 to 1:17; and the API and the SPIM are in a weight ratio range of 1:0.05 to 1:1.7.

[0145] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 2 to 4% by weight of an antitussive, preferably dextromethorphan; (ii) 2 to 5% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 29 to 31% by weight of a lipid; (iv) 38 to 43% by weight of a surfactant; and (v) 20 to 22% by weight of a solvent, with respect to the formulation.

[0146] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent, with a proviso that if API is an analgesic preferably tapentadol, in a weight range of 2 to 10%(w / w), then the SPIM is in a weight range of 0.5 to 15%(w / w), the lipid is in a weight range of 10 to 58%(w / w), the surfactant is in a weight range of 10 to 55%(w / w), the solvent is in weight range of 12 to 63%(w / w), with respect to the formulation.

[0147] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinationsthereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent, with a proviso that if API is an analgesic preferably tapentadol, in a weight range of 2 to 10%(w / w), then the SPIM is in a weight range of 0.5 to 15%(w / w), the lipid is in a weight range of 10 to 58%(w / w), the surfactant is in a weight range of 10 to 55%(w / w), the solvent is in weight range of 12 to 63%(w / w), with respect to the formulation.

[0148] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 2 to 10% by weight of an analgesic, preferably tapentadol; (ii) 0.5 to 15% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 10 to 58% by weight of a lipid; (iv) 10 to 55% by weight of a surfactant; and (v) 12 to 63% by weight of a solvent, wherein the API and the solvent are in a weight ratio range of 1:3 to 1:8; the API and the lipid are in a weight ratio range of 1:1 to 1:21; the API and the surfactant are in a weight ratio range of 1:1 to 1:17; the API and the SPIM are in a weight ratio range of 1:0.2 to 1:2.

[0149] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 2 to 10% by weight of an analgesic, preferably tapentadol; (ii) 5 to 15% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 15 to 20% by weight of a lipid; (iv) 11 to 14% by weight of a surfactant; and (v) 45 to 57% by weight of a solvent, with respect to the formulation.

[0150] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent, with a proviso that if API is vitamin, in a weight range of 1 to 10%(w / w), then the SPIM is in a weight range of 1 to 7%(w / w), the lipid is in a weight rangeof 4 to 62%(w / w), the surfactant is in a weight range of 10 to 58%(w / w), the solvent is in weight range of 10 to 40%(w / w), with respect to the formulation.

[0151] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent, with a proviso that if API is vitamin, in a weight range of 1 to 10%(w / w), then the SPIM is in a weight range of 1 to 7%(w / w), the lipid is in a weight range of 4 to 62%(w / w), the surfactant is in a weight range of 10 to 58%(w / w), the solvent is in weight range of 10 to 40%(w / w), with respect to the formulation.

[0152] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 10% by weight of a vitamin, preferably cholecalciferol or vitamin D3; (ii) 1 to 7% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 10 to 58% by weight of a surfactant; and (v) 10 to 40% by weight of a solvent, , wherein the API and the solvent are in a weight ratio range of 1:3 to 1:17; the API and the surfactant are in a weight ratio range of 1:1 to 1:27.5; the API and the lipid are in a weight ratio range of 1:0.4 to 1:30.8; and the API and the SPIM are in a weight ratio range of 1:0.3 to 1:2.

[0153] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 2 to 6% by weight of a vitamin, preferably cholecalciferol or vitamin D3; (ii) 1 to 3% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 49 to 62% by weight of a lipid; (iv) 20 to 24% by weight of a surfactant; and (v) 10 to 19% by weight of a solvent, with respect to the formulation.

[0154] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, otherdrugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent, with a proviso that if API is factor Xa inhibitor preferably apixaban, in a weight range of 1 to 8%(w / w), then the SPIM is in a weight range of 1 to 10%(w / w), the lipid is in a weight range of 5 to 30%(w / w), the surfactant is in a weight range of 5 to 36%(w / w), the solvent is in weight range of 50% to 80%(w / w), with respect to the formulation.

[0155] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent, with a proviso that if API is factor Xa inhibitor preferably apixaban, in a weight range of 1 to 8%(w / w), then the SPIM is in a weight range of 1 to 10%(w / w), the lipid is in a weight range of 5 to 30%(w / w), the surfactant is in a weight range of 5 to 36%(w / w), the solvent is in weight range of 50% to 80%(w / w), with respect to the formulation.

[0156] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 8% by weight of a Factor Xa inhibitors, preferably apixaban; (ii) 1 to 10% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 5 to 30% by weight of a lipid; (iv) 5 to 36% by weight of a surfactant; and (v) 50 to 80% by weight of a solvent, wherein the API and the solvent are in a weight ratio range of 1:10 to 1:34.1; the API and the surfactant are in a weight ratio range of 1:0.5 to 1:21; the API and the lipid are in a weight ratio range of 1:0.5 to 1:10; and the API and the SPIM are in a weight ratio range of 1:0.05 to 1:3.

[0157] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 2 to 4% by weight of a Factor Xa inhibitors, preferably apixaban; (ii) 2 to 4% by weight of a specialised polymericinterfacial modifier (SPIM); (iii) 9 to 15% by weight of a lipid; (iv) 5 to 8% by weight of a surfactant; and (v) 70 to 76% by weight of a solvent.

[0158] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) 1 to 30% by weight of an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 4 to 62% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 80% by weight of a solvent, with a proviso that if API is selected from other drugs preferably atorvastatin, Rosuvastatin, aspirin, or diclofenac, in a weight range of 2 to 25%(w / w), then the SPIM is in a weight range of 1 to 12%(w / w), the lipid is in a weight range of 5 to 45%(w / w), the surfactant is in a weight range of 5 to 58%(w / w), the solvent is in weight range of 5 to 35%(w / w), with respect to the formulation.

[0159] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising: (i) an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; (ii) 0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) a lipid; (iv) a surfactant; and (v) a solvent, with a proviso that if API is selected from other drugs preferably atorvastatin, Rosuvastatin, aspirin, or diclofenac, in a weight range of 2 to 25%(w / w), then the SPIM is in a weight range of 1 to 12%(w / w), the lipid is in a weight range of 5 to 45%(w / w), the surfactant is in a weight range of 5 to 58%(w / w), the solvent is in weight range of 5 to 35%(w / w), with respect to the formulation.

[0160] In an embodiment of the present disclosure, there is provided a stable oral pro-dispersion formulation, comprising 2 to 25% by weight of API selected from other drugs preferably atorvastatin, Rosuvastatin, aspirin, or diclofenac; (ii) 1 to 12% by weight of a specialised polymeric interfacial modifier (SPIM); (iii) 5 to 45% by weight of a lipid; (iv) 5 to 58% by weight of a surfactant; and (v) 5 to 35%by weight of a solvent, wherein the API and the solvent are in a weight ratio range of 1:0.2 to 1:34.1; the API and the surfactant are in a weight ratio range of 1:0.5 to 1:27.5; the API and the lipid are in a weight ratio range of 1:0.4 to 1:30.8; and the API and the SPIM are in a weight ratio range of 1:0.02 to 1:4.6.

[0161] In an embodiment of the present disclosure, there is provided a process of preparing the formulation as disclosed herein, the process comprising the steps of: (i) adding one or more SPIM, one or more lipids, one or more solvent with an API and optionally adding at least one pharmaceutically acceptable excipient selected from biodegradable polymer, stabilizers, or combinations thereof, and mixing thoroughly to obtain a clear solution of a first mixture; and (ii) adding one or more surfactants to the first mixture and optionally at least one pharmaceutically acceptable excipient selected from biodegradable polymer, stabilizers, or combinations thereof and processing to form the formulation.

[0162] In an embodiment of the present disclosure, there is provided a capsule, comprising the pro-dispersion formulation as disclosed herein, wherein the capsule is a shell made of a material selected from gelatin, hydroxypropyl methylcellulose, acrylic polymer, acid resistant polymer, natural polymer, vegan or vegetarian shell, or combinations thereof. Examples of shell materials also include but not limited to modified starches, carrageenans, pullulans, pectins, and behenates.

[0163] In an embodiment of the present disclosure, there is provided a capsule, wherein the capsule has a moisture content in a weight range of 1 to 10%(w / w), with respect to total weight of the capsule.

[0164] In an embodiment of the present disclosure, there is provided a capsule, wherein the capsule dissolves when in contact with the gastro-intestinal tract (GIT) or its contents or its fluids, and the formulation is spontaneously converted into carrier particles entrapping the API.

[0165] In an embodiment of the present disclosure, there is provided a capsule, wherein the carrier particle entrapping the API has a particle size in the range of 5 nm to 10 pm.

[0166] In an embodiment of the present disclosure, there is provided a capsule, wherein the carrier particle entrapping the API has an entrapment efficiency of 50% to 90%.

[0167] In an embodiment of the present disclosure, there is provided a capsule, wherein the carrier particle entrapping the API is physically stable for a time period in the range of 3h to 6h in a simulated gastric / GIT pH conditions.

[0168] In an embodiment of the present disclosure, there is provided a process of preparing the capsule as disclosed herein, the process comprising filling the prodispersion formulation as disclosed herein into a shell to obtain the capsule.

[0169] In an embodiment of the present disclosure, there is provided use of the formulation as disclosed herein or capsule as disclosed herein, for treating or managing a condition. The term “condition” as used herein refers to any illness, disorder, disease, or injury that affects the normal functioning of the body or mind.

[0170] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, the method comprising treating with the pro-dispersion formulation as disclosed herein or the capsule as disclosed herein.

[0171] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, wherein the condition is selected from acute pain, chronic pain, fever, inflammatory conditions, osteoarthritis, rheumatoid arthritis, musculoskeletal pain, diabetic neuropathy, cough, common cold, flu, depression, major depressive disorder, thromboembolism, atrial fibrillation, venous thromboembolism, acute coronary syndrome, arterial thrombosis, coronary and peripheral artery disease, cardiovascular risk reduction prophylaxis, treatment of deep vein thrombosis after abdominal, hip replacement, knee joint replacement surgery, or vitamin deficiency.

[0172] In an embodiment of the present disclosure, there is provided use or method of treatment or management of a condition in a subject in need thereof, wherein the formulation or the capsule is administered once or twice a day for treating or managing the condition.

[0173] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, wherein the condition is selected from pain (acute and chronic), fever, and inflammatory conditions, which include osteoarthritis and rheumatoid arthritis, provided the API in the formulation or capsule as disclosed herein is NSAID, preferably ibuprofen.

[0174] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, wherein the condition is selected from cough caused by common cold, flu, depression or major depressive disorder, provided the API in the formulation or capsule as disclosed herein is antitussive, preferably dextromethorphan.

[0175] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, wherein the condition is selected from common cold, flu or other related conditions, provided the API in the formulation or capsule as disclosed herein is analgesic, preferably tapentadol.

[0176] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, wherein the condition is selected from treatment of deficiency or supplement or any disease state because of particular vitamin deficiency, provided the API in the formulation or capsule as disclosed herein is vitamin, preferably vitamin D3.

[0177] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, wherein the condition is selected from thromboembolism, Atrial fibrillation, venous thromboembolism, acute coronary syndrome, or arterial thrombosis, coronary and peripheral artery disease, cardiovascular risk reduction prophylaxis and treatment of deep vein thrombosis after abdominal, hip replacement or knee joint replacement surgery, provided the API in the formulation or capsule as disclosed herein is factor Xa inhibitor, preferably apixaban.

[0178] In an embodiment of the present disclosure, there is provided a method of treatment or management of a condition in a subject in need thereof, wherein the condition is selected from acute pain, chronic pain, fever, inflammatory conditions,osteoarthritis, rheumatoid arthritis, musculoskeletal pain, diabetic neuropathy, cough, common cold, flu, depression, major depressive disorder, thromboembolism, atrial fibrillation, venous thromboembolism, acute coronary syndrome, arterial thrombosis, coronary and peripheral artery disease, cardiovascular risk reduction prophylaxis, treatment of deep vein thrombosis after abdominal, hip replacement, knee joint replacement surgery, or vitamin deficiency, provided the API in the formulation or capsule as disclosed herein is selected from other drugs, preferably selected from atorvastatin, rosuvastatin, aspirin, or diclofenac.

[0179] Although the subject matter has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the subject matter, will become apparent to persons skilled in the art upon reference to the description of the subject matter. It is therefore contemplated that such modifications can be made without departing from the spirit or scope of the present subject matter as defined.EXAMPLES

[0180] The disclosure will now be illustrated with following examples, which is intended to illustrate the stable of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may vary.EXAMPLE 1EXAMPLE 1.1: Preparation of the pro-dispersion formulation:

[0181] The pro-dispersion formulation was prepared by adding one or more specialised polymeric interfacial modifier (SPIM), one or more lipids, one or more solvent with an API and optionally adding at least one pharmaceutically acceptable excipient selected from biodegradable polymer, stabilizers, or combinations thereof, followed by thorough mixing to obtain a clear solution of a first mixture. To the first mixture, one or more surfactants and optionally a pharmaceutically acceptable excipients were added and mixed with high shear processor to obtain the pro-dispersion formulation.EXAMPLE 1.2; Preparation of the capsule comprising the pro-dispersion formulation:

[0182] The pro-dispersion formulation prepared using the method described in Example 1.1 is in the form of a pro-nano liquid concentrate or pro-nano system, which is encapsulated in a softgel, hardgel, or any other type of capsule shell to form a capsule. Upon contact with the gastrointestinal tract (GIT) and its fluids, its contents, the capsule dissolved and released the pro-dispersion liquid concentrate. This concentrate then spontaneously transformed into carrier particles that encapsulate the drug. The resulting carrier particles remained physically stable for up to 6 hours within the GIT under simulated gastrointestinal conditions or varying pH conditions.EXAMPLE 2: PREPARATION OF A PRO-DISPERSION FORMULATION COMPRISING IBUPROFEN, NSAID AS AN APIExample 2.1: Preparation Method 1 (Eg. 1 to Eg. 10)

[0183] The formulations (Eg. 1 to Eg. 10) were prepared by the method as described herein. BHT (stabilizer), poloxamer 188 (SPIM), cetostearyl alcohol and stearic acid (lipids) and polyvinyl pyrrolidone (SPIM), were added to benzyl alcohol, propylene glycol, and / or ethanol (solvents), PEG 600 (SPIM), and mixed thoroughly to obtain a clear solution. To the clear solution, Ibuprofen and MCT (medium chain triglycerides, lipid) were added and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Alpha tocopherol (stabilizer), polyoxyl-40-hydrogenated castor oil and polysorbate 80(surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising Ibuprofen. Table 1.1 depicts the composition of the pro-dispersion formulation, Eg. 1 to 10 comprising Ibuprofen, NSAID as an API and mentioned components in said weight percentages, prepared using the method described in Example 2.1.Table 1.1: Composition of the pro-dispersion formulation comprising Ibuprofen,NSAID as an API prepared using the method described in Example 2.1Example 2.2 Preparation Method 2 (Eg. 11 to Eg. 18)

[0184] BHT (stabilizer) was added to benzyl alcohol (solvent), PEG 600(SPIM), phospholipid and TPGS (SPIM) and mixed until clear solution wasobtained. To the clear solution, Ibuprofen (API) and MCT (lipid) were added and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Alpha tocopherol (stabilizer), polyoxyl-40-hydrogenated castor oil and polysorbate 80 (surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprisingIbuprofen, NSAID as an API. Table 1.2 depicts the composition of the prodispersion formulation, Eg. 11 to 18 comprising Ibuprofen, NSAID as an API prepared using the method described in Example 2.2. Table 1.2: Composition of the pro-dispersion formulation comprising Ibuprofen, NSAID as an API prepared using the method described in Example 2.2Example 2.3: Preparation Method 3 (Eg. 19 to Eg. 23)

[0185] BHT (stabilizer) was added to benzyl alcohol (solvent) and PEG 600 (SPIM) and mixed thoroughly to obtain a clear solution. To the clear solution, Ibuprofen and MCT (lipid) were added and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Alpha tocopherol (stabilizer), polyoxyl-40-hydrogenated castor oil and polysorbate 80 (surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising Ibuprofen, NSAID as an API. Table 1.3 depicts the composition of the pro-dispersion formulation, Eg. 19 to 23 comprising Ibuprofen, NSAID as an API prepared using the method described in Example 2.3. Table 1.3: Composition of the pro-dispersion formulation comprising Ibuprofen, NSAID as an API prepared using the method described in Example 2.3EXAMPLE 3: PREPARATION OF A PRO-DISPERSION FORMULATION COMPRISING DEXTROMETHORPHAN, ANTITUSSIVE AS AN API:Example 3.1: Preparation Method 1 (Eg. 24 to Eg. 32)

[0186] BHT (stabilizer), cetostearyl alcohol(lipid) and lecithin, ascorbyl palmitate, TPGS and polyvinylpyrrolidone (SPIM), were added to benzyl alcohol, propylene glycol, and / or polyethylene glycol 200 (mixture of solvents) and mixed until dissolved completely to obtain a clear solution. To the clear solution, dextromethorphan (API), oleic acid and MCT (lipids) were added and mixedcontinuously under controlled conditions until a clear solution of a first mixture was obtained. Polyoxyl 40 hydrogenated castor oil and polysorbate 80 (surfactants) were added to the first mixture and mixed with high shear processor to obtain the prodispersion formulation comprising dextromethorphan, antitussive as an API. Table 2.1 depicts the composition of the pro-dispersion formulation, Eg. 24 to 32 comprising dextromethorphan, antitussive as an API prepared using the method described in Example 3.1.Table 2.1: Composition of the pro-dispersion formulation comprising dextromethorphan, antitussive as an API prepared using the method described in Example 3.1Example 3.2: Preparation Method 2 (Eg. 33 to Eg. 40)

[0187] BHT(stabilizer), poloxamer (SPIM), phospholipid (lipid), were added to benzyl alcohol, PEG 200 (solvents) (mixture of solvents) and mixed until dissolved completely to obtain a clear solution. To the clear solution, dextromethorphan (API), oleic acid and MCT (lipids) were added and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Alpha tocopherol (stabilizer), polyoxyl 40 hydrogenated castor oil and polysorbate 80 (surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising dextromethorphan, antitussive as an API. Table 2.2 depicts the composition of the pro-dispersion formulation, Eg. 33 to 40 comprising dextromethorphan, antitussive as an API prepared using the method described in Example 3.2.Table 2.2: Composition of the pro-dispersion formulation comprising dextromethorphan, antitussive as an API prepared using the method described in Example 3.2EXAMPLE 4: PREPARATION OF A PRO-DISPERSION FORMULATION COMPRISING TAPENTADOL, ANALGESIC AS AN API: (Eg. 41 to Eg. 50)

[0188] BHT (stabilizer), poloxamer 407 / lecithin (SPIM), alpha tocopherol (stabilizer), cholesterol, cetostearyl alcohol, phospholipid (lipids) and / or PEG 32 stearate (SPIM) were added to benzyl alcohol, propylene glycol, polyethylene glycol 200 (solvents) and mixed for a while followed by addition of polyvinyl pyrrolidone (biodegradable polymer) and mixed continuously until dissolved to obtain a clear solution. To the clear solution, tapentadol (API), oleic acid and MCT (lipids) were added and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Polyoxyl-40-hydrogenated castor oil and polysorbate 80 (surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising tapentadol, analgesic as an API. Table 3 depicts the composition of the pro-dispersion formulation, Eg. 41 to 50 comprising tapentadol, analgesic as an API prepared using the method described in Example 4.Table 3: Composition of the pro-dispersion formulation comprising tapentadol, analgesic as an API prepared using the method described in Example 4.EXAMPLE 5: PREPARATION OF A PRO-DISPERSION FORMULATION COMPRISING STATINS, ASPIRIN, AND DICLOFENAC, ANALGESIC AS AN API: (Eg. 51 to Eg. 55)

[0189] Alpha Tocopherol, BHT (stabilizers), cetostearyl alcohol and cholesterol (lipids) were added to benzyl alcohol, polyethylene glycol 200, ethanol, and propylene glycol (solvents), polyvinyl pyrrolidone (SPIM), and methoxy polyethylene glycol 2000 (SPIM), and mixed until dissolved, followed by addition of lecithin(SPIM) or phospholipid (lipid) and poloxamer (SPIM) and mixed continuously until dissolved to obtain a clear solution. To the clear solution, either of the API selected from atorvastatin, rosuvastatin, aspirin, or diclofenac sodium (API), along with caprylic acid, oleic acid, and MCT (lipids) were added and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Polyoxyl-40-hydrogenated castor oil and polysorbate 80 (surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising atorvastatin, rosuvastatin, aspirin, diclofenac sodium, analgesic as an API. Table 4 depicts the composition of the prodispersion formulation, Eg. 51 to 55 comprising atorvastatin, rosuvastatin, aspirin, diclofenac sodium, analgesic as an API prepared using the method described in Example 5.Table 4: Composition of the pro-dispersion formulation comprising atorvastatin, rosuvastatin, aspirin, diclofenac sodium, analgesic as an API prepared using the method described in Example 5EXAMPLE 6: PREPARATION OF A PRO-DISPERSION FORMULATION COMPRISING VITAMIN D3 AS AN API: (Eg. 56 to Eg. 62)

[0190] BHT (stabilizer), poloxamer (SPIM) and polyvinylpyrrolidone (SPIM) were added to benzyl alcohol (solvent) and oleic acid (lipid) and mixed continued until dissolved to obtain a clear solution. To the clear solution, vitamin D3 was added and mixed thoroughly until clear followed by addition of soybean oil and MCT (lipids) were added and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Polyoxyl-40-hydrogenated castor oil, polysorbate 80 (surfactants) and poloxamer (SPIM) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising vitamin D3 as an API. Table 5 depicts the composition of the pro-dispersion formulations, Eg. 56 to 62 comprising vitamin D3 as an API prepared using the method described in Example 6.Table 5: Composition of the pro-dispersion formulation comprising vitamin D3, as an API prepared using the method described in Example 6.EXAMPLE 7: PREPARATION OF A PRO-DISPERSION FORMULATION COMPRISING APIXABAN, FACTOR Xa INHIBITOR AS AN API: Example 7.1: Preparation Method 1 (Eg. 63 to Eg. 67)

[0191] BHT (stabilizer), poloxamer and TPGS (SPIM) and apixaban (API) were dissolved in benzyl alcohol (solvent) using high shear mixer until a clear solution of a first mixture was obtained. MCT, oleic acid (lipids) alpha tocopherol (stabilizer), polysorbate 80 and polyoxyl 35 Hydrogenated castor oil (surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising apixaban, factor Xa inhibitor as an API. Table 6.1 depicts the composition of the pro-dispersion formulation, Eg. 63 to 67 comprising apixaban, factor Xa inhibitor as an API prepared using the method described in Example 7.1. Table 6.1: Composition of the pro-dispersion formulation comprising apixaban, factor Xa inhibitor as an API prepared using the method described in Example 7.1Example 7.2: Preparation Method 2 (Eg. 68 to Eg. 73)

[0192] BHT (stabilizer), poloxamer (SPIM), sucrose palmitate, sucrose acetate isobutyrate (SPIM) and apixaban (API) were dissolved in benzyl alcohol and / or propylene glycol, Polyethylene glycol 300 (solvents) using high shear mixer to obtain a clear solution. To the clear solution, cetostearyl alcohol, phospholipid, MCT and oleic acid (lipids) and mixed continuously under controlled conditions until a clear solution of a first mixture was obtained. Polyoxyl 40 hydrogenated castor oil, polyoxyl 35 hydrogenated castor oil and polysorbate 80 (surfactants) were added to the first mixture and mixed with high shear processor to obtain the pro-dispersion formulation comprising apixaban, factor Xa inhibitor as an API.Table 6.2 depicts the composition of the pro-dispersion formulation, Eg. 68 to 73 comprising apixaban, factor Xa inhibitor as an API prepared using the method described in Example 7.2.

[0193] Table 6.2 Composition of the pro-dispersion formulation comprising apixaban, factor Xa inhibitor as an APIEXAMPLE 8: ANALYSIS OF THE FORMULATIONS (Eg. 1 to 73)

[0194] The prepared formulations were tested for their stability under five different conditions of temperature and pH: i) At room temperature (RT): The freshly prepared formulations kept at RT were evaluated. ii) Simulated gastric condition: The formulations were contacted with 0.1N HC1, simulating a gastric pH for a time period of up to 6h. iii) Simulated gastrointestinal tract condition: The formulations were contacted with buffers having a pH of 6.2 and 7.4 for a time period of up to 6h.iv) Accelerated conditions as per ICH guidelines'. The formulations were exposed to a temperature of 40°C and 75% relative humidity for a time period of up to 6 months. v) Long term stability as per ICH guidelines'. The formulations were exposed to a temperature of 30°C and 75% relative humidity for a time period of up to 24 months.

[0195] The stability of the formulations was assessed by evaluating both the particle size distribution and the polydispersity index (PDI) under five different conditions. These two factors are commonly used to gauge the stability of particlebased formulations, especially in the context of dispersions or emulsions containing active pharmaceutical ingredients (APIs).

[0196] Particle Size Distribution: The distribution of particle sizes within a formulation is crucial for understanding its physical stability. If the particle sizes remained consistent over time, it indicated that the formulation is stable, as there was no significant aggregation or growth of particles. In this study, the particle size distribution of the formulation remained unaltered across the five conditions, suggesting that the formulation was stable under those conditions. A stable particle size distribution means that the formulation is less likely to undergo changes such as particle coalescence or precipitation, which could negatively affect the API's performance or delivery.

[0197] Poly dispersity Index (PDI): The PDI is a measure of the width of the particle size distribution and is a critical indicator of homogeneity. A PDI value ranges from 0 to 1, where a lower PDI indicated a more uniform particle size distribution, and a higher PDI indicated a broader range of particle sizes. A PDI value approaching zero suggested that the particles were more monodisperse (uniform in size), which was desirable for maintaining formulation stability. In this study, as the PDI value stayed closer to zero, it indicated that the particle size of the formulation remained consistent over time. This consistency in particle size is important because it suggested that the particles were not aggregating, which would otherwise lead to a shift in particle size distribution. The PDI can be determinedusing instruments that use Dynamic Light Scattering or photon correlation spectroscopy or determined through electron microscopy.

[0198] A key implication of maintaining a constant particle size distribution and a low PDI is that the formulation is likely free from crystallization. Crystallization of the API would lead to the growth of larger particles, which could change the overall particle size distribution and disrupt the formulation. In the context of pharmaceutical formulations, crystallization of the API reduced bioavailability or compromised the stability and effectiveness of the drug. The fact that the particle size remained constant and the PDI remained low under the tested conditions strongly suggested that the API did not undergo crystallization, further confirming the enhanced stability of the formulation.

[0199] Furthermore, the formulations exposed to the condition (i) to (iv), were subjected to physical observations under microscope to check for drug crystallization if any and depicted in Figures 1 to 6 and 8 to 22. The formulations were hydrated with appropriate amount of purified water, for particle size testing, for Transmission Electron Microscopic analysis and the formulation as such was used for assay test and other chemical testing.

[0200] The entrapment efficiency of the loaded API was calculated for each formulation. The pro-dispersion formulation (PDF) was first diluted with 0.22pm filtered deionized water to create a particulate dispersion (PD), which was then used to evaluate drug entrapment efficiency. A fixed volume of this PD, mixed with an equal volume of filtered deionized water, was transferred into the feed hopper of a Tangential Flow Filtration (TFF) unit equipped with a lOOKDa filter membrane capsule. The diluted dispersion was passed through the TFF capsule, and a fixed volume of filtrate was collected, while the remaining retentate was separated. This process was repeated if necessary, and the pooled samples were collected. Both the filtrate and retentate were analyzed using HPLC (with a validated fit-for-purpose method) to determine the amounts of entrapped and un-entrapped drug, and a mass balance was calculated to confirm the method's validity. The retentate contained the entrapped drug within the carrier particles, while the free drug remained in the filtrate. Additionally, a total-drug assay of the formulation was conducted using avalidated HPLC method. The entrapment efficiency of the particulate dispersion was then calculated using a specific formula.

[0201] The assay percentage for each formulation referred to the measurement of the actual amount of the active pharmaceutical ingredient (API) present in a formulation compared to the theoretical or expected amount. It is an important quality control test that helped to determine the content uniformity, potency, and consistency of the drug formulation. To evaluate the assay percentage validated HPLC method for the specific drug was used.Example 8.1: Analysis of the properties of the formulations comprising Ibupro en as an API (Eg. 1 to 23)

[0202] The formulations containing Ibuprofen as the active pharmaceutical ingredient (API) were observed for crystal formation and the corresponding stability of the formulations were assessed. It was observed that the formulations Eg. 8, 11, 12, 13, 19, 20, 21, and 23 were found to be less stable / unstable due to the presence of API crystals (When PDF is added to GIT pH medium) evident from the corresponding photomicrographs (physical observations under microscope), as shown in Figures 1 to 6. In Eg. 8, 11, 12, and 13, crystals formed after two days at room temperature (RT), as shown in Figure 1 (Eg. 11) and Figure 2 (Eg. 13). For Eg. 19, 20, 21, and 23, drug crystals were observed within 24 hours at RT. However, Eg. 9 showed no crystals for over six months at RT, and Eg. 2 showed no crystals for up to two years at RT and under long-term ICH conditions (30°C / 75%RH), as shown in Figure 3. Figure 24A depicts transmission electron microscopy (TEM) images of formed nanoparticles when ibuprofen pro-dispersion formulation (Eg. 2) was hydrated with purified water.

[0203] Additionally, crystals formed immediately after adding formulations to simulated gastric pH (0.1N HC1) in Eg. 19 and 20, as evident in Figures 4 and 5. In contrast, no crystals were seen in Eg. 9 (Figure 6). Factors such as higherconcentrations of API (32% in Eg. 8), absence of solvent (Eg. 11), lesser solvent concentration (Eg. 12: 1.9%, Eg. 13: 3.1%), lack of lipid (Eg. 19), absence of surfactant (Eg. 21), or higher surfactant concentration (Eg. 23: 62%) contributed to the crystallization of the API under various temperature and pH conditions.

[0204] Accordingly, the stable formulations, Eg. 1, 2, 3, 4, 5, 6, 7, 9, 10, and 22(where no crystal formation was observed), were further subjected to stability testing and the results depicted in Table 7.1. The stability results of Eg. 2 under conditions described in EXAMPLE 8 have been represented in Table 7.2, 7.3, and 7.4. Table 7.1: Particle size distribution of the formulations comprising Ibuprofen as an API atRTTable 7.2: Stability of the prepared formulation comprising Ibuprofen (Eg. 2) as an API, exposed to long term (30°C / 75%RH) up to 24 Months and Accelerated Conditions (40°C / 75%RH) up to 6 Months:Table 7.3: Stability of the prepared formulation comprising Ibuprofen (Eg. 2) as an API exposed to 0.1N HCl (simulated gastric acid / pH) up to 6 hoursTable 7.4: Stability of the prepared formulation comprising Ibuprofen (Eg. 2) as an API exposed to GIT pH conditions (pH 6.2 & pH 7.4 buffers) up to 6 hours.Example 8.2: Analysis of the properties of the formulations comprising Dextromethorphan as an API (Eg. 24 to 40)

[0205] The formulations containing dextromethorphan as the active pharmaceutical ingredient (API) were observed for crystal formation and the corresponding stability of the formulations were assessed. It was observed that the formulations Eg. 30, 31, 39, 40 were found to be less stable / unstable, due to apparent sedimentation and precipitation, as evident from Figures 8 to 11 and Eg.36, 37, 38, 39 due to the presence of API crystals evident from the corresponding photomicrographs (physical observations under microscope) Figures 13 to 16. After 48 hours at room temperature (RT), visible sedimentation of precipitate was detected in Eg. 30 (Figure 11). Additionally, precipitation occurred in Eg. 31 (Figure 8), while phase separation along with precipitation was observed in Eg. 40(Figure 9). Crystals and precipitation were present in Eg. 39 (Figure 10). In stark contrast, Eg. 24 (Figure 12) remained completely clear and transparent, with nosigns of crystals or precipitation for up to 6 months at room temperature. Furthermore, Eg. 24 maintained its stability under accelerated ICH conditions of 40°C / 75%RH, without any crystallization or precipitation, indicating superior formulation stability compared to the other formulations. Further TEM image of formed nanoparticles when dextromethorphan pro-dispersion formulation (Eg. 26) was hydrated with purified water is shown in Figure 24B.

[0206] Photomicrographs revealed the presence of API crystals when the exposed to simulated gastric pH (in vitro) in Eg. 36 (Figure 13), 37 (Figure 14), 38 (Figure 15), and 39 (Figure 16). In contrast, no drug crystals were observed in Eg. 24 (Figure 17). Factors such as higher concentrations of SPIM (32% in Eg. 31), absence of solvent (Eg. 36), lower solvent concentration (Eg. 37: 1.25%), lack of lipid (Eg. 38), absence of surfactant (Eg. 39), or higher surfactant concentrations (65.8%, Eg. 40), contributed to the precipitation, sedimentation or crystallization of the API under various temperature and pH conditions.

[0207] Accordingly, the stable formulations, Eg. 24, 25, 26, 27, 28, 29, 32, 33, 34, and 35 (where no precipitation, sedimentation or crystal formation was observed), were subjected to stability testing under conditions described in EXAMPLE 8 and the results have been represented in Table 8.1, 8.2, 8.3, 8.4 and 8.5.Table 8.1: Stability of the prepared formulation comprising dextromethorphan (Eg. 24 and 25) as an API exposed accelerated conditions (40°C / 75%RH) for up to 6 monthsTable 8.2: Stability of the prepared formulation comprising dextromethorphan (Eg. 26) as an API exposed to long term (30°C / 75%RH) up to 18M and at Accelerated Conditions (40°C / 75%RH) up to 6 MonthsTable 8.3: Stability of the prepared formulation comprising dextromethorphan (Eg. 24) as an API exposed to 0.1N HCl (gastric acid / pH) up to 3 hoursTable 8.4: Stability of the prepared formulation comprising dextromethorphan (Eg. 24) as an API exposed to GIT pH condition (pH 6.2 & pH 7.4 buffers) up to 6 hoursTable 8.5: Particle size distribution of the formulations comprising dextromethorphan (Eg. 27 to 29 and 32 to 35) and formulation comprising Tapentadol (Eg. 45 and 48) as an API.Example 8.3: Analysis of the properties of the formulations comprising Tapentadol as an API (Eg. 41 to 50)

[0208] The formulations containing Tapentadol as the active pharmaceutical ingredient (API) were observed for crystal formation and the corresponding stability of the formulations were assessed. It was observed that the formulations Eg. 46, 47, 49, and 50 were found to be less stable / unstable in due to the presence of API crystals evident from the corresponding photomicrographs (physical observations under microscope), Figures 18 to 20. Drug crystals were observed immediately after exposure to gastric pH in Eg. 46, 47, 49 and 50. The photomicrographs indicate the presence of API crystals under the microscope when exposed to gastric pH (in vitro) in Eg. 47 (Figure 18). In Eg. 46 (Figure 19), large crystal particles were visible, whereas Eg. 41 (Figure 20) showed no signs of drug crystals, indicating a stable formulation. Factors such as lower concentration of solvent (9.51%) and higher lipid concentration (62.69%) in Eg. 46, lower lipid concentration (3.2% in Eg. 47), lower surfactant concentrations (Eg. 49: 4%), or absence of SPIM (Eg. 50) contributed to the crystallization of the API under various temperature and pH conditions.

[0209] Accordingly, the stable formulations, Eg. 41 to 45 and 48 (where no crystal formation was observed), were subjected to stability testing under conditions described in EXAMPLE 8 and the results have been represented in Table 8.5, 9.1 to 9.5.Table 9.1: Stability of the formulation comprising Tapentadol as an API (Eg. 41 ) exposed to long term (30°C / 75%RH) up to 18M and at Accelerated Conditions (40°C / 75%RH) up to 6MTable 9.2: Stability of the formulation comprising Tapentadol as an API (Eg. 42 and 43) exposed to Accelerated conditions (40°C / 75%RH) up to 6 monthsTable 9.3: Stability of the formulation comprising Tapentadol as an API (Eg. 41 to 43) exposed to 0.1 N HCl (Gastric acid / pH) up to 6 hoursParticle Size Change uith Time in 0.1 N I ICI (Gastric pl I)Table 9.4: Stability of the formulation comprising Tapentadol as an API (Eg. 41 ) exposed to GIT pH 6.2 & 7.4 buffers up to 6 hoursTable 9.5: Particle size distribution of the formulations comprising Tapentadol as an API (Eg. 44) at RTExample 8.4: Analysis of the properties of the formulations comprising statins, aspirin and diclofenac as an API (Eg. 51 to 55)

[0210] The stable formulations comprising statins, aspirin and diclofenac as anAPI, Eg. 51 to 55 (where no crystal formation was observed), were subjected to stability testing under conditions described in EXAMPLE 8 and the results are presented in Table 10.1 to 10.3.Table 10.1: Stability of the formulations comprising Atorvastatin as an API (Eg. 51 ) exposed to Accelerated Conditions (40°C / 75%RH) for up to 6 monthsTable 10.2: Stability of the formulations comprising Rosuvastatin as an API (Eg.52) exposed to 0.1N HCl (simulated gastric acid / pH) up to 12 hoursTable 10.3: Particle size distribution of the formulations comprising Aspirin andDiclofenac as an API (Eg. 53 to 55) in purified waterExample 8.5: Analysis of the properties of the formulations comprising Vitamin D3 as an API (Eg. 56 to 62)

[0211] The formulations containing vitamin D3 as the active pharmaceutical ingredient (API) were observed for crystal formation and the corresponding stability of the formulations were assessed. It was observed that the formulation Eg. 56 was found to be less stable / unstable, due to apparent precipitation, owing to the absence of solvent in the formulation. Accordingly, the stable formulations (where no precipitation was observed), Eg. 57 to 62, were subjected to stability testing under conditions described in EXAMPLE 8 and the results have been represented in Table 11.1. Table 11.1: Particle size distribution of the formulation comprising Vitamin D3 as an API (Eg. 57 to 62) at RTExample 8.6: Analysis of the physical properties of the formulations comprising Apixaban as an API (Eg. 63 to 73)

[0212] The formulations containing apixaban as the active pharmaceutical ingredient (API) were observed for crystal formation and the corresponding stability of the formulations were assessed. It was observed that the formulation Eg. 67 was found to be less stable / unstable, due to the presence of API crystals evident from the corresponding photomicrographs (physical observations under microscope) Figure 21. The photomicrographs revealed the presence of API crystals under the microscope when exposed to the simulated gastric pH (in vitro) in Eg. 67 (Figure 21). In contrast, no drug crystals were observed in Eg. 63 (Figure 22). Factors such as higher concentrations of solvent (85%), lower concentrations of lipids (3.7%), and lower concentrations of surfactant (3.2%) in Eg. 67 contributed to the crystallization of the API under various temperature and pH conditions.

[0213] Accordingly, the stable formulations, Eg. 63 to 66 and 68 to 73 (where no crystal formation was observed), were subjected to stability testing under conditions described in EXAMPLE 8 and the results have been represented in Table 12.1 to 12.7.Table 12.1: Stability of the prepared formulation comprising Apixaban as an API (Eg. 63) exposed to Accelerated conditions (40°C / 75%RH) for up to 6 Months and Long-term conditions 30°C / 75%RH & 25°C / 60%RH for up to 18 MonthsTable 12.2: Stability of the prepared formulation comprising Apixaban as an API (Eg. 64) exposed to Accelerated Conditions (40°C / 75%RH)Table 12.3: Stability of the prepared formulation comprising Apixaban as an API (Eg. 63) exposed to 0.1N HCl I Gastric acid / Stomach acid (Gastric pH) for up to 6 HrsTable 12.4: Stability of the prepared formulation comprising Apixaban as an API (Eg. 63) exposed to GIT pH (pH 6.2 buffer and pH 7.4 buffer) for upto 6 hoursTable 12.5: Particle size distribution of the formulation comprising Apixaban as an API (Eg. 65, 66, 68 to 72) at RTTable 12.6: Particle size distribution of the formulation comprising Apixaban as an API (Eg. 73) at RTTable 12.7 Addition of Purified water from 0% to 10%w / w (water uptake capacity) to Apixaban Pro-dispersion Formulation (Eg. 63) and Particle size distribution of formed carrier particles on hydration of PDFResults:

[0214] The evaluation of the formulations comprising the different API, revealed a particle size ranging from 5 nm to 10pm, and a PDI value in the range of 0 to 1. The small particle size and low PDI values of the stable formulations indicated awell-dispersed, stable API, reducing the likelihood of crystallization. This stability facilitated the bioavailability of the drug, ensuring its therapeutic efficacy. The high assay percentages (98-102%) further confirmed that the API remained intact and maintained its potency over time, supporting the formulation's long-term stability. Overall, the formulations of the present disclosure were effective and stable, without the risk of crystallization or loss of potency. The formulations showed a considerably good API entrapment efficiency of >90% (50 to 90%), which suggested that the formulations are highly efficient in retaining the drug within the delivery system, leading to better therapeutic outcomes, as a larger proportion of the drug is available for its intended purpose.EXAMPLE 9: Effect of concentration of Specialized Polymeric Interfacial Modifier (SPIM) in the prepared formulations:

[0215] The presence of Specialized Polymeric Interfacial Modifiers (SPIM) into formulations significantly altered the zeta potential, impacting the stability, dispersion, and bioavailability of the system. In colloidal dispersions, zeta potential (ZP) is also scientifically called as electrokinetic potential, zeta potential is the potential difference between the dispersion medium and the stationary layer of fluid attached to the dispersed particle. Zeta potential measures charge on the surface of the particle and surface charge density which is amount of charge per unit area on surface of particle.

[0216] Zeta potential is a measure of charge density or surface charge on the particles, generally strong electrical repulsion between particles prevent them from aggregation.

[0217] Accordingly, the formulations were diluted with appropriate amount of filtered (0.22pm) de-ionised water and the zeta potential was measured (in Zeta- Potential mode) using Zetasizer, Malvern Instruments, UK. The results are depicted in Table 13 for the stable formulations for each API, viz. Eg. 9 (Ibuprofen), 26 (dextromethorphan), 57 (Vitamin D3), and 64 (Apixaban) and the corresponding zetapotential values are shown in Table 13. Figure 7 is a graphical representation showing the effect of SPIM concentration in the formulation Eg. 14 to 18 on zetapotential and the corresponding zetapotential values are shown in Table 14. On increasing the concentration of SPIM from 9.4% to about 26.6%, there was an increase in zeta potential (ZP) value from - 17.7mV to - 12.0mV, which is about 32% increase in ZP value.

[0218] It is evident from the Table 14 that a significant increase in the magnitude of the zeta potential value or surface charge density (ranging from 17% to 29%) was observed when SPIM was added to the formulations (Eg. 9, 26, 57, and 64) at concentrations ranging from 2% to 10.75%, compared to the formulations without SPIM (0% SPIM). These observations clearly indicated that the SPIM altered the surface orientation of the particles, which underscored its role in modifying the physical and electrostatic properties of the formulation. Based on SPIM interaction with the particle surfaces, the stability of the formulation is increased and showed improved performance in terms of bioavailability, and efficacy.Table 13: Estimated zeta potential for the formulations Eg. 9, 26, 57, and 64Table 14 : Estimated zeta potential for the formulations Eg. 14 to 18 with respect to varying SP1M concentration.EXAMPLE 10: EVALUATION OF GASTRIC ULCEROGENIC POTENTIAL ACTIVITY OF FORMULATION COMPRISING IBUPROFEN (Eg. 2) IN RATS

[0219] NSAIDs (like Ibuprofen) could cause serious gastrointestinal (GI) side effects, including gastric ulcers, gastritis, bleeding, and perforation, especially when taken in high doses or long-term. The risk is higher in older individuals, those with poor health, smokers, heavy alcohol drinkers, and people with pre-existing GI conditions. To assess a drug’s potential to cause gastric ulcers, an ulcerogenic potential study was conducted in small animals, such as rats.

[0220] In the study, Swiss Albino Wistar Rats were randomly assigned to two groups, each containing 6 rats. Group 1 received a high dose (~5 times the normal dose) of 150 mg / kg body weight of Ibuprofen-PDF (Eg. 2), while Group 2 (the control group) was administered normal saline. Both groups fasted for 15 hours post-dosing. After this period, the rats were sacrificed, and their stomach tissues were removed, opened along the greater curvature, and examined for ulcers or lesions (both incidence and severity) using a binocular microscope at 10X magnification. The ulcers were photographed, and the ulcerogenic potential was evaluated based on score-of-ulceration, the ulcerogenic potential activity(ulceration index / ulceration score) was calculated using internationally acceptable ulcer scoring criteria.Results

[0221] The ulcerogenic potential study (based on ulceration scores) in rats showed that the formulation, Eg. 2 at a dose of 150 mg / kg (Figure 23A) did not cause any gastric ulcers in rats, with results comparable to those of the control group (normal saline) (Figure 23B). These findings suggested that the pro-dispersion formulation of the present disclosure had a very low / no propensity of causing gastrointestinal damage. This study clearly indicated that the formulation effectively addressed one of the major gastrointestinal side effects commonly caused by the APIs.ADVANTAGES OF THE PRESENT DISCLOSURE

[0222] The present disclosure provides a stable oral pro-dispersion formulation with the following advantages:1. No API crystallization (Physical Stability): preventing crystallization, ensures that the API remains in a stable state, which is indicated by a low Polydispersity Index (PDI) and uniform particle size throughout the shelf-life.2. Higher assay percentage (Chemical Stability) indicates a higher concentration of the active ingredient, long-term chemical stability of API, (Assay), ensuring better therapeutic effectiveness.3. High Entrapment Efficiency (Entrapment): maximizes the entrapment of the API in the formulation, improving its stability, controlled release and improved bioavailability4. The formulations exhibit desirable technical attributes like shelf-stability, GIT- stability, sustained action, better absorption, and minimal gastro-intestinal toxicity.5. Simple and cost-effective manufacturing process.

Claims

I / We Claim:

1. A stable oral pro-dispersion formulation, comprising: i.an active pharmaceutical ingredient (API) selected from non-steroidal anti-inflammatory drugs (NSAIDs), antitussives, analgesics, factor Xa inhibitors, vitamins, other drugs, derivatives, or combinations thereof; ii.0.1 to 30% by weight of a specialised polymeric interfacial modifier (SPIM); iii.a lipid; iv.a surfactant; and v.a solvent.

2. The formulation as claimed in claim 1, wherein the formulation comprises 1 to 30% by weight of the active pharmaceutical ingredient; 4 to 62% by weight of the lipid; 5 to 58% by weight of the surfactant; and 5 to 80% by weight of the solvent.

3. The formulation as claimed in claim 1, wherein the API is selected from ibuprofen, naproxen, mefenamic acid, piroxicam, meloxicam, tenoxicam, aspirin, diclofenac, aceclofenac, etodolac, indomethacin, sulindac, ketoprofen, etoricoxib, celecoxib, dextromethorphan, benzonatate, pentoxyverine, methadone, normethadone, levodropropizine, tapentadol, codeine, fentanyl, hydrocodone, meperidine, naloxone or naltrexone, oxycodone, morphine, apixaban, rivaroxaban, edoxaban, betrixaban, fondaparinux, idraparinux, otamixaban, letaxaban, darexaban, antithrombin alfa, vitamins, vitamin D3, telmisartan, azilsartan, candesartan, irbesartan, olmesartan, valsartan, losartan, eprosartan, axitinib, dasatinib, erlotinib, imatinib, nilotinib, pazopanib, sunitinib, gefitinib, sorafenib, nintedanib, capecitabine, cladribine, fludarabine, 5-fluorouracil, gemcitabine, cytarabine, pemetrexed, methotrexate, pralatrexate, floxuridine, decitabine, clofarabine, nelarabine, simvastatin, lovastatin, atorvastatin, pitavastatin, pravastatin, fluvastatin, rosuvastatin, cerivastatin, cyclosporine, everolimus, tacrolimus, sirolimus, mycophenolate mofetil, progesterone, testosterone, levothyroxine, estradiol, danazol, fexofenadine, loratadine, domperidone, ondansetron,palonosetron, aprepitant, netupitant, gabapentin, pregabalin, mirogabalin, baclofen, other GABA derivatives, hormones, their salts, solvates, derivatives, or combinations thereof.

4. The formulation as claimed in claim 1, wherein the SPIM is selected from poloxamers, polyvinyl compounds, polyvinylpyrrolidones or its derivatives, polyethylene glycol derivatives having molecular weight greater than 350 g / mol, phospholipids, polyoxyethylene fatty acid esters, sucrose esters, phosphatidylcholines or its derivatives thereof, tocopherol esters, D-a- tocopheryl polyethylene glycol succinate (TPGS) or derivatives thereof, ascorbic acid esters, pegylated compounds, pegylated lipids, or combinations thereof.

5. The formulation as claimed in claim 1, wherein the API and the SPIM are in a weight ratio range of 1:0.02 to 1:4.6.

6. The formulation as claimed in claim 1, wherein the lipid is selected from fats, cholesterol, long chain triglycerides, medium-chain triglycerides, fatty acids, fatty alcohols, fatty acid esters of glycerol, glyceryl stearate, oils, propylene glycol laurate, or combinations thereof.

7. The formulation as claimed in claim 1, wherein the API and the lipid are in a weight ratio range of 1:0.4 to 1:30.8.

8. The formulation as claimed in claim 1, wherein the surfactant is selected from fatty acid esters of sorbitan, polyoxyl hydrogenated castor oil, polyoxyethylene esters / polysorbates, fatty acid esters, polyglycerol esters, propylene glycol fatty acid esters, sulfate-based surfactants, sulfonate -based surfactants, their derivatives, or combinations thereof.

9. The formulation as claimed in claim 1, wherein the API and the surfactant are in a weight ratio range of 1:0.5 to 1:27.5.

10. The formulation as claimed in claim 1, wherein the solvent is selected from alcohols, benzyl alcohol, ethanol, propylene glycol, polyethylene glycols having molecular weight less than 350 g / mol, propyl ethylene glycol ethers, propylene glycol esters, caprylocaproyl macrogolglycerides, their derivatives, or combinations thereof.

11. The formulation as claimed in claim 1, wherein the API and the solvent are in a weight ratio range of 1:0.2 to 1:34.1.

12. The formulation as claimed in claim 1, wherein the formulation comprises a pharmaceutically acceptable excipient selected from biodegradable polymers, stabilizers, or combinations thereof.

13. The formulation as claimed in claim 12, wherein the biodegradable polymer is selected from polyvinyl alcohol, polylysines, polyglycines, cellulose or derivatives thereof, polyethylene -based polymers, hyaluronate or derivatives thereof, natural gums, or combinations thereof.

14. The formulation as claimed in claim 12, wherein the stabilizer is selected from sodium bisulfite, butylated hydroxy toluene (BHT), butylated hydroxy anisole (BHA), sodium / potassium metabisulfite, tocopherols, uric acid, lipoic acid, ascorbic acid, tert-Butylhydroquinone (TBHQ), propyl gallate, or combinations thereof.

15. The formulation as claimed in claim 1, wherein the formulation is substantially free of water and has a moisture content not more than 5% by weight.

16. The formulation as claimed in claim 1, wherein the formulation has a shelflife in a range of 18 to 24 months at ICH conditions.

17. The formulation as claimed in claim 1, wherein the formulation shows no ulcerogenic potential.

18. The formulation as claimed in claim 1, wherein the formulation is in the form of a nano-dispersion, nano-emulsion, colloidal dispersion, dispersion, emulsion, solubilized liquid, liquid, gel, concentrate, colloidal dispersion, liquid adsorbed onto a substrate, or nanoparticles.

19. A process of preparing the formulation as claimed in claim 1, the process comprising the steps of: i. adding one or more SPIM, one or more lipids, one or more solvent with an API and optionally adding at least one pharmaceutically acceptable excipient selected from biodegradable polymer, stabilizers, or combinations thereof, and mixing thoroughly to obtain a clear solution ofa first mixture; and ii. adding one or more surfactants and optionally adding at least one pharmaceutically acceptable excipient selected from biodegradable polymer, stabilizers, or combinations thereof, to the first mixture and processing to form the formulation.

20. A capsule, comprising the formulation as claimed in claim 1.

21. The capsule as claimed in claim 20, wherein the capsule is a shell made of a material selected from gelatins, hydroxypropyl methylcellulose, cellulose polymers, acrylic polymers, acid-resistant polymers, natural polymers, polyols, vegan or vegetarian shell materials, or combinations thereof.

22. The capsule as claimed in claim 20, wherein the capsule has a moisture content in a weight range of 1 to 10% (w / w), with respect to total weight of the capsule.

23. The capsule as claimed in claim 20, wherein the capsule dissolves when in contact with the gastro-intestinal tract (GIT) or its contents and the formulation is spontaneously converted into carrier particles entrapping the API.

24. The capsule as claimed in claim 23, wherein the carrier particle entrapping the API has a particle size in a range of 5 nm to 10 pm.

25. The capsule as claimed in claim 23, wherein the carrier particle entrapping the API has an entrapment efficiency of 50% to 90%.

26. The capsule as claimed in claim 23, wherein the carrier particle entrapping the API is physically stable for a time period in the range of 3h to 6h in a simulated gastric / GIT pH conditions.

27. A process of preparing the capsule as claimed in claim 20, the process comprising filling the pro-dispersion formulation as claimed in claim 1 into a shell to obtain the capsule.

28. Use of the formulation as claimed in claim 1 or capsule as claimed in claim 20, for treating or managing a condition.

29. A method of treatment or management of a condition in a subject in need thereof, the method comprising treating with the formulation as claimed in claim 1 or the capsule as claimed in claim 20.

30. The use or method as claimed in claim 28 or 29, wherein the condition is selected from acute pain, chronic pain, fever, inflammatory conditions, osteoarthritis, rheumatoid arthritis, musculoskeletal pain, diabetic neuropathy, cough, common cold, flu, depression, major depressive disorder, thromboembolism, atrial fibrillation, venous thromboembolism, acute coronary syndrome, arterial thrombosis, coronary and peripheral artery disease, cardiovascular risk reduction prophylaxis, treatment of deep vein thrombosis after abdominal, hip replacement, knee joint replacement surgery, or vitamin deficiency.

31. The use or method as claimed in claim 28 or 29, wherein the formulation claimed in claim 1 or the capsule as claimed in claim 20 is administered once or twice a day or as specified by physician, for treating or managing the condition.

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