Oral solid dosage compositions comprising maleated natural oils, and use thereof

Abstract

An oral solid dosage composition comprising a reaction product of (i) a maleated natural oil comprising natural oil with maleated functionality, and (ii) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moiety, hydrophobic moiety, and combinations thereof is provided in the present disclosure. Also provided are binder compositions and coating compositions for oral solid dosage forms, comprising the reaction product of the present disclosure.

Description

Docket No.: 4478PCTORAL SOLID DOSAGE COMPOSITIONS COMPRISING MALEATED NATURAL OILS, AND USE THEREOFFIELD OF THE INVENTION

[0001] The presently disclosed process(es), procedure(s), method(s), product(s), result(s), and / or concept(s) (collectively referred to hereinafter as the “present disclosure”) relates generally to an oral solid dosage composition(s) comprising modified natural oils. The present disclosure further relates to a coating composition(s) for oral solid dosage forms.

[0002] Natural oils are abundant, inexpensive, and derived from sustainable sources. They are promising raw materials for the synthesis of renewable compounds such as polymers, plastics, and plasticizers. Natural oils are generally blends of different triglycerides, the esterification product of fatty acids and glycerol, and contain varying degrees of unsaturation (i.e., double bonds). Oils can be characterized by hydroxyl value and fatty acid composition. A difficulty with utilizing natural oils is that they are blends of triglycerides containing varying degrees of unsaturated double bonds which are relatively unreactive. To make these natural oils reactive, the unsaturated double bonds are generally chemically modified to make them reactive. For example, these unsaturated bonds can be reacted to provide natural oils chemically modified / functionalized with epoxide functional groups and / or succinic anhydride functional groups. These chemical modifications allow the further addition of hydroxyl containing species onto the natural oils. The modified natural oils may be non-dispersible in water or alcohol. As a result, these oils can be incorporated into compositions for a wide variety of applications, including personal care, such as hair care, sun care, skin care and oral care; adhesives; coatings; paints; electronics; household, industrial and institutional (HI& I) compositions; inks; membranes; metal working fluids; oilfield chemicals; plastics and plasticizers; textiles; industrial products; biocides; pharmaceuticals; nutraceuticals; and agrochemical compositions.

[0003] US Patent 9809538B2 describes a modified natural compound synthesized from an epoxidized natural fatty acid, maleated natural fatty acid, epoxidized natural oil, or maleated natural oil and a lactam compound having at least one hydroxyl group, wherein the modified natural compound has utility in, e.g., adhesive or beverage compositions.Docket No.: 4478PCT

[0004] US Patent No. 10889693 B2 teaches a composition including a modified oil alkyl ester and / or modified oil aryl ester having the transesterification reaction product of an oil (soybean oil) and a surfactant having hydroxy group.

[0005] PCT Application Publication WO2024197173, assigned to ISP Investments, teaches a dispersant composition including a reaction product of a maleated natural oil, a base, and a functionalized or unfunctionalized moiety that encompasses hydrophobic moieties or hydrophilic moieties, or combinations thereof.

[0006] Despite the renewability, biodegradability, sustainability, and beneficial functions provided by natural fatty acids, natural oils, and their maleated counterparts, they exhibit properties that can limit their application. For example, maleated soybean oil is insoluble and non-dispersible in water and alcohols. As a result, these oils may tend to exude or phase-separate from formulated compositions. This feature makes their formulation more difficult, often requiring additional ingredients to facilitate dissolution, emulsification, or dispersion. Natural and maleated natural oils may not impart the desired properties needed in end-uses, such as solubilization capability, glass transition temperature, flexibility, shine, and / or plasticization. Consequently, the performance (including, but not limited to stability, resistance to phase separation, absorption, clean-up, solubility potential, staining potential, lubrication, film formation, uniformity of spreading, comedogenic tendency, ease of removal), may be less than desired. Finally, although such natural oils are an important renewable material, they are not always the formulator's first choice, and, in fact, often are not considered at all.

[0007] Accordingly, there is still a need for further improvement of modified natural oils to overcome the limitations in their properties and to expand the various compositions derived therefrom.

[0008] Further, coatings play a major role in many industry segments such as pharmaceuticals, veterinary, agricultural, nutritional, automotive, biochemical, chemical, computers, consumer goods, food, electronics, materials, and healthcare. The widespread application of coatings is attributed to the diverse functionalities they provide, such as protection (e.g., from water absorption, ultra-violet damage), separation (e.g., chemical incompatibility), altered release of active ingredients (e.g., immediate, extended, delayed, controlled release) and modification of the sensory perception (e.g., smoothness / roughness, taste, and texture). One specific application ofDocket No.: 4478PCTcoatings is in the oral solid dosage (OSD) form, where they play a critical role in enhancing the stability, appearance, and functionality of pharmaceutical products. Currently available commercial pharmaceutical coating technology includes spraying of a dilute polymer solution over the OSD forms or tablets, leading to a time-consuming and high cost drying process. To overcome these problems, coatings with high solid content are proposed. For the last few years, however, coating systems with solids content in the range of 10 to 35 % w / w have been available. The use of coatings with sprayable solid content in excess to 35 % w / w can significantly reduce the coating processing time and energy, resulting in significant cost saving.

[0009] United States Patent No. 12,098,291, assigned to ISP Investments LLC, teaches a colorant coating composition having total solids content of 20 wt.% to 35 wt. % comprising hydroxypropyl cellulose (HPC), PVP / VA copolymer, polydextrose as a film forming agent, polyethylene glycol, and medium chain triglycerides (MCT).

[0010] Although high-solids coatings offer faster processing and drying times, they typically have the disadvantage of high viscosity and result in coarse and rough coatings with low gloss. Thus, there is a need for high-solids coating composition with faster processing times, improved gloss and low surface roughness.SUMMARY OF THE INVENTION

[0011] In one aspect, the present disclosure provides an oral solid dosage (OSD) composition comprising a reaction product of: (i) a maleated natural oil comprising a natural oil with maleated functionality; and (ii) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof.

[0012] In another important aspect, the present disclosure provides an oral solid dosage composition comprising a reaction product of: a maleated soybean oil; and behenyl alcohol, polyethylene glycol monomethyl ether or a combination thereof.

[0013] In yet another important aspect, the present disclosure provides an oral solid dosage composition comprising a reaction product of: (i) a maleated soybean oil; (ii) behenyl alcohol; and (iii) polyethylene glycol monomethyl ether. In still another non-limiting embodiment of the present disclosure, the reaction product further comprises at least one additional moiety selected from theDocket No.: 4478PCTgroup consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0014] In yet another important aspect, the present disclosure provides reaction product comprising one or more structures selected from the following group of structures:, wherein n is about 20 to about 200 or, from about 40 to about 100, and Me is methyl.

[0015] In yet another important aspect, the present disclosure provides an oral solid dosage composition further comprising at least one ingredient selected from the group consisting of an active pharmaceutical ingredient, a filler, a binder, a surfactant, a disintegrating agent, a lubricant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0016] In another important aspect, the present disclosure provides a granule composition comprising: (i) the reaction product according to the present disclosure; and (ii) at least one active pharmaceutical ingredient. In one non-limiting embodiment of the present disclosure, the reaction product is present in an amount from about 5.0 wt.% to about 20.0 wt.% of the total granule composition weight, and the active pharmaceutical ingredient is present in an amount from about 80.0 wt.% to about 95.0 wt.% of the total granule composition weight. In one non-limitingDocket No.: 4478PCTembodiment of the present disclosure, the granule composition functions as a binder or a binding agent.

[0017] In another important aspect, the present disclosure provides an oral solid dosage composition comprising: (i) the granule composition of the present disclosure; and (ii) at least one additional ingredient selected from the group consisting of a filler, an additional binder, a surfactant, a disintegrating agent, a lubricant, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0018] In yet another important aspect, the present disclosure provides a coating composition for an oral solid dosage form comprising: (i) the reaction product of (a) a maleated natural oil comprising a natural oil with maleated functionality; and (b) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof; and (ii) at least one ingredient selected from the group consisting of a surfactant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0019] In a further aspect, the present disclosure provides a coating composition for a pharmaceutical tablet comprising: (i) the reaction product of (a) a maleated natural oil comprising a natural oil with maleated functionality; and (b) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof; and (ii) at least one ingredient selected from the group consisting of a surfactant, a film forming agent, a plasticizer, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.Docket No.: 4478PCTBRIEF DESCRIPTION OF THE FIGURES

[0020] Further embodiments of the present application can be understood with the appended figures.

[0021] FIG. 1 shows tablet coated with the present coating composition of Example 25 having the reaction product of Example Bl with a total solid content of (A) 40% w / w; and (B) 50% w / w.

[0022] FIG. 2 shows A) a comparative coating composition 1; B) a comparative coating composition 2; C) comparative coating composition 1 finished-coated tablets; and D) comparative coating composition 2 finished-coated tablets.

[0023] FIG. 3 shows viscosity profile of comparative coating compositions vs. the present coating composition of Example 25.

[0024] FIG. 4 shows finished coated tablet with (A) 50% w / w present coating composition of Example 25; B) Copovidone-HPC coating (Comparative coating 3); and C) PVA coating (Comparative coating 4).

[0025] FIG. 5 shows coating time comparison of the present coating composition of Example 25 vs. comparative coatings 3 and 4.Docket No.: 4478PCTDETAILED DESCRIPTION OF THE INVENTION

[0026] Before explaining at least one embodiment of the inventive concept(s) in detail by way of exemplary drawings, experimentation, results, and laboratory procedures, it is to be understood that the inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings, experimentation and / or results. The inventive concept(s) is / are capable of other embodiments or of being practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary - not exhaustive. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

[0027] Unless otherwise defined herein, scientific, and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art.

[0028] All of the compositions and / or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the inventive concept(s) as defined by the appended claims.

[0029] As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

[0030] As used herein, the term “polymer” refers to a compound comprising repeating structural units (monomers) connected by covalent chemical bonds. Polymers may be further derivatized, crosslinked, grafted or end capped. Non-limiting examples of polymers include copolymers, terpolymers, tetra polymers, quaternary polymers, and homologues. The term “copolymer” refers to a polymer consisting essentially of two or more different types of monomers polymerized to obtain the copolymer.Docket No.: 4478PCT

[0031] As used herein, the term “reaction product” refers to a substance produced from a chemical reaction of one or more reactant substances.

[0032] As used herein, the term “natural oil” refers to compounds comprising triglycerides and may contain varying levels of fatty acids, monoglycerides, or diglycerides. These oils are derived from plants or animal sources. Natural oils also include fatty acid glyceryl esters, which are synthesized by reacting glycerol with 1, 2, or 3 molar equivalents of a fatty acid or a mixture of fatty acids. These compounds can be mono, di or triglycerides of a single fatty acid or a mixture of fatty acids.

[0033] As used herein, the terms, “maleated natural oil” or “natural oil with maleated functionality”, can be used interchangeably without limiting the scope of the present disclosure, and refer to natural oil comprising at least one maleated functionality. Accordingly, the term "maleation" as used hereafter should be understood to mean "introduction of maleted functionality by covalent chemical reaction." The term “maleated” means “possessing covalently attached maleated functionality.”

[0034] As used herein, the term “hydrophilic moiety” refers to a hydrophilic molecule or portion of a hydrophilic molecule that has a tendency to react with another chemical entity to increase the hydrophilicity of such chemical entity. Examples include, but are not limited to, hydrophilic polyether glycols, hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether polyamines, and hydrophilic polyether amine monoalkyl ethers.

[0035] As used herein, the term “hydrophobic moiety” refers to a hydrophobic molecule or portion of a hydrophobic molecule that has a tendency to react with another chemical entity to increase the hydrophobicity of such chemical entity. Examples include, but are not limited to, hydrophobic alcohols, hydrophobic amines, or silicone-based compounds.

[0036] As used herein, the term, “maleated functionality” refers to moieties formed by attaching maleic anhydride to unsaturated fatty acyl chains, found in natural oils, by ene reaction. “Maleated functionality” includes, but is not limited to, the cyclic anhydride form (I), the diacid form (II), the disodium dicarboxylate form (III), other dicarboxylate salt forms, and the half ester form (IV). Since the carbon-carbon double bond of maleic anhydride becomes a saturated carbon-carbon single bond during the ene reaction, the “maleated functionality” pictured in I, II, III, and IV mightDocket No.: 4478PCTalso be called by one of ordinary skill in the art succinic anhydride, succinic acid, succinate salt, or succinate half ester functionality.oxVoI II III IV

[0037] As used herein, the term “functionalized” with reference to any moiety refers to the presence of one or more functional groups in a moiety. Various functional groups may be introduced in the moiety by way of one or more functionalization reactions known to a person having ordinary skill in the art. Non-limiting examples of functionalization reactions include: alkylation, epoxidation, sulfonation, hydrolysis, amidation, esterification, hydroxylation, dihydroxylation, amination, ammonolysis, acylation, nitration, oxidation, dehydration, elimination, hydration, dehydrogenation, hydrogenation, acetalization, halogenation, dehydrohalogenation, Michael addition, aldol condensation, Canizzaro reaction, Mannich reaction, Claisen condensation, Suzuki coupling, and the like. In one non-limiting embodiment of the present disclosure, the term “functionalized” with reference to any moiety refers to the presence of one more functional group selected from the group consisting of alkyl, alkenyl, hydroxyl, carboxyl, halogen, alkoxy, amino, imino, and combinations thereof.

[0038] As used herein, the term “hydrocarbyl” includes straight-chain and branched-chain alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl groups, and combinations thereof with optional heteroatom (s). A hydrocarbyl group may be mono-, di- or polyvalent and have carbon chains containing 2 to 100 carbon atoms.

[0039] As used herein, the term “alkyl” refers to a functionalized or unfunctionalized, monovalent, straight-chain, branched-chain, or cyclic C1-C60 hydrocarbyl group optionally having one or more heteroatoms. In one non-limiting embodiment, an alkyl is a C1-C45 hydrocarbyl group. In another non-limiting embodiment, an alkyl is a C1-C30 hydrocarbyl group. Non-limiting examples of alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tertbutyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl, 2-ethylhexyl, tert-octyl, iso-norbornyl, n-dodecyl, tert-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, n-eicosyl, cyclobutyl, cyclopentyl,Docket No.: 4478PCTcyclohexyl, and the like. The definition of “alkyl” also includes groups obtained by combinations of straight-chain, branched-chain and / or cyclic structures.

[0040] As used herein, the term “aryl” refers to a functionalized or unfunctionalized, monovalent, aromatic hydrocarbyl group optionally having one or more heteroatoms. The definition of aryl includes carbocyclic and heterocyclic aromatic groups. Non-limiting examples of aryl groups include phenyl, naphthyl, indenyl, indanyl, azulenyl, fluorenyl, anthracenyl, furyl, thienyl, pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furanyl, 2,3-dihydrobenzofuranyl, benzo[b]thiophenyl, IH-indazolyl, benzimidazolyl, benzthiazolyl, purinyl, 4H-quinolizinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxyazinyl, pyrazolo[l,5-c]triazinyl, and the like.

[0041] As used herein, the term “aralkyl” refers to an alkyl group comprising one or more aryl substituent(s) wherein "aryl" and "alkyl" are as defined above. Non-limiting examples of aralkyl groups include benzyl, 2-phenylethyl, 3 -phenylpropyl, 4-phenylbutyl, 5 -phenylpentyl, 4-phenylcyclohexyl, 4-benzylcyclohexyl, 4-phenylcyclohexylmethyl, 4-benzylcyclohexylmethyl, and the like.

[0042] As used herein, the term “alkaryl” refers to an aryl group substituted with one or more alkyl groups, such as, for example, 2-methylphenyl, 3-methylphenyl, 4-m ethylphenyl, 4-ethylphenyl, 4-nonylphenyl, 3-nonylphenyl, dimethylphenyl, or trimethylphenyl, which may optionally be further substituted on one or more of the carbon atoms of the radical.

[0043] As used herein, the term “alkylene” refers to a functionalized or unfunctionalized, divalent, straight-chain, branched-chain, or cyclic C1-C40 hydrocarbyl group optionally having one or more heteroatoms. In one non-limiting embodiment, an alkylene is a C1-C30 group. In another non-limiting embodiment, an alkylene is a C1-C20 group. Non-limiting examples of alkylene groups include:CH3_CH2— — CH2— CH2—-—CH—CH2—Docket No.: 4478PCT

[0044] As used herein, the term “arylene” refers to a functionalized or unfunctionalized, divalent, aromatic hydrocarbyl group optionally having one or more heteroatoms. The definition of arylene includes carbocyclic and heterocyclic groups. Non-limiting examples of arylene groups include phenylene, naphthylene, pyridinylene, and the like.

[0045] As used herein, the term “heteroatom” refers to oxygen, nitrogen, sulfur, silicon, phosphorous, or halogen. The heteroatom(s) may be present as a part of one or more heteroatomcontaining functional groups. Non-limiting examples of heteroatom-containing functional groups include ether, hydroxy, epoxy, carbonyl, carboxamide, carboxylic ester, carboxylic acid, imine, imide, amine, sulfonic, sulfonamide, phosphonic, and silane groups. The heteroatom(s) may also be present as a part of a ring such as in heteroaryl and heteroarylene groups.Docket No.: 4478PCT

[0046] In one aspect, the present disclosure provides an oral solid dosage (OSD) composition comprising a reaction product of: (i) a maleated natural oil comprising a natural oil with maleated functionality; and (ii) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof.

[0047] In one non-limiting embodiment, the maleated natural oil or the natural oil with maleated functionality used to generate the reaction product comprised by the present oral solid dosage composition includes a natural oil comprising at least one maleated functionality. Suitable examples of such natural oils with maleated functionality include, but are not limited to, maleated avocado oils, maleated coconut oils, maleated corn oils, maleated cottonseed oils, maleated jojoba oils, maleated linseed oils, maleated nut oils, maleated olive oils, maleated palm oils, maleated raisin oils, maleated rapeseed oils, maleated safflower oils, maleated sesame oils, maleated soybean oils, maleated squash oils, maleated sunflower oils, maleated almond oils, maleated canola oils, maleated flaxseed oils, maleated grapeseed oils, maleated palm kernel oils, maleated peanut oils, maleated walnut oils, maleated chickpea oils, maleated clary sage oils, and mixtures thereof. In one non-limiting embodiment of the present disclosure, the maleated natural oil is a maleated soybean oil.

[0048] Further, the maleated natural oil or natural oil with maleated functionality according to the present disclosure may be prepared by the maleation of a natural oil. During maleation, one or more of an α,β-unsaturated carboxylic acid or anhydride thereof, for example, maleic anhydride reacts with unsaturated fatty acyl chains present in natural oils. The maleation of natural oils can occur under heating in three different ways. The first one is known as “Ene” reaction (reaction between an allylic moiety and an enophile in a pericyclic reaction), obtaining a triglyceride structure with anhydride moieties (succinic anhydride). The second one is a radical addition, which consumes a double bond in the fatty acid, incorporating the succinic anhydride into the natural oil structure. The final reaction is also a radical addition that incorporates the maleic anhydride into the natural oil structure without consuming C=C bonds (fatty acid chain and maleic anhydride); this reaction occurs due to abstraction of hydrogen atoms from two alkenes groups.

[0049] The preparation of maleated natural oils is well known to a person skilled in the art. Accordingly, the maleated natural oils as used for the purpose of the present disclosure may be prepared by methods known in the related arts. In one non-limiting embodiment of the presentDocket No.: 4478PCTdisclosure, the maleic anhydride and at least one natural oil may be reacted together at elevated temperatures. In one non-limiting embodiment of the present disclosure, the maleation is carried out at a temperature varying in the range of from about 150 °C to about 300 °C. In another nonlimiting embodiment of the present disclosure, the maleation is carried out at a temperature varying in the range of from about 170 °C to about 230 °C, or from about 200 °C to about 220 °C.

[0050] Further, the maleation may be carried out for a time period varying from about 0.5 hours to about 14 hours. In one non-limiting embodiment of the present disclosure, the maleation is carried out for a time period varying from about 1 hour to about 5 hours, or from about 2 hours to about 6 hours, or from about 6 hours to 10 hours.

[0051] During maleation, the mole ratio of maleic anhydride to natural oil may be equal to 1. In one non-limiting embodiment of the present disclosure, the mole ratio varies from about 1 to about 2, or from about 1 to about 2.8, or from about 1 to about 3.2 moles of maleic anhydride for each mole of natural oil.

[0052] The maleated natural oil is further reacted with at least one of functionalized or unfunctionalized moieties selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and their combinations, to form the present reaction product.

[0053] In one non-limiting embodiment of the present disclosure, the functionalized or unfunctionalized moiety may be a hydrophobic moiety. In another non-limiting embodiment of the present disclosure, the functionalized or unfunctionalized moiety may be a hydrophilic moiety. In one non-nonlimiting embodiment of the present disclosure, the hydrophilic or hydrophobic moieties are those of hydrocarbyl alcohols or hydrocarbyl amines.

[0054] The hydrocarbyl alcohols are the alcohols characterized by hydroxyl group (-OH) attached to a carbon of a hydrocarbyl group. As used herein, the term “hydrocarbyl” refers to a group that contains carbon and hydrogen atoms. Suitable and non-limiting examples of hydrocarbyl group include, but are not limited, straight-chain and branched-chain alkyl groups, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, aryl group, and combinations thereof. Further, the hydrocarbyl group may be with or without heteroatoms. Further, the hydrocarbyl group may be mono-, di- or polyvalent and may have carbon chains ranging from 2 to 100 carbon atoms.Docket No.: 4478PCT

[0055] Further, the hydrocarbyl alcohols may be classified as primary, secondary and tertiary alcohols, based on the number of carbon atoms connected to the carbon atom bearing the hydroxyl group. Each classification of alcohol may have a general formula. For example,the general formula for primary alcohols isOHH–C–HAthe general formula for secondary alcohols isOHR'–C–H, andthe general formula for tertiary alcohols isOHR’-A-R"A, wherein R, R1and R" stand for different alkyl, alkylene, alkynyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, or arylene groups. In one non-limiting embodiment of the present disclosure, the hydrocarbyl alcohol may be a monohydric alcohol or a dihydric alcohol, or a polyhydric alcohol.

[0056] In one non-limiting embodiment of the present disclosure, the hydrophobic moiety is that of a hydrocarbyl alcohol having from about 6 to about 36 carbon atoms. In another nonlimiting embodiment of the present disclosure, the hydrocarbyl alcohol may have from about 6 to about 24 carbon atoms (hereafter referred to as hydrophobic alcohols). Further, the hydrocarbyl alcohol may be a linear or branched, saturated or unsaturated, aliphatic or aromatic, and monofunctional or multifunctional alcohol.

[0057] In one non-limiting embodiment of the present disclosure, the hydrophobic alcohol is selected from the group consisting of unsubstituted or substituted alkyl, alkylene, alkynyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, or arylene alcohols, with or without heteroatoms. Suitable examples of such hydrophobic alcohols include, but are not limited to, hexanol, heptanol, nonanol, decanol, dodecanol, phenol, ethylbenzyl alcohol, 2-ethyl-l -hexanol, 1 -octanol, 2-octanol, 2-butyl-Docket No.: 4478PCT1 -octanol, 2-octyl-l -dodecyl alcohol, 1 -tetradecanol, 2-tetradecanol, 1 -hexadecanol, 2-hexadecanol, 1-octadecanol 3,7-dimethyl-l-octanol, 2-propyl-l -pentanol, 4-methyl-l -pentanol, cetyl alcohol, stearyl alcohol, eicosanol, behenyl alcohol, and combinations thereof. In another non-limiting embodiment of the present disclosure, the hydrophobic alcohol is behenyl alcohol.

[0058] Similar to the hydrocarbyl alcohols, hydrocarbyl amines are the amines characterized by an amine group (-NH2) attached to a carbon of a hydrocarbyl group. The hydrocarbyl amines may be classified as primary, secondary and tertiary amines, based on the number of carbon atoms or carbon groups connected to the nitrogen atom. Each classification of amines may have a general formula, for example,the general formula for primary amine isH-N-HR1the general formula for secondary amine isRl-N-HR2, andthe general formula for tertiary amines isR1–N–R3R2, wherein R1, R2, and R3stand for different alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, or alkaryl groups.

[0059] In one non-limiting embodiment of the present disclosure, the hydrocarbyl amine is selected from the group consisting of primary amines, secondary amines and combinations thereof.

[0060] In one non-limiting embodiment of the present disclosure, the hydrophobic moiety is that of a hydrocarbyl amine having from about 6 to about 36 carbon atoms. In another non-limiting embodiment of the present disclosure, the hydrocarbyl amine may have from about 10 to about 24 carbon atoms (hereafter referred to as hydrophobic amines). Further, the hydrophobic amine may be a linear or branched, saturated or unsaturated, aliphatic or aromatic, and monofunctional or multifunctional amine. In one non-limiting embodiment of the present disclosure, the hydrophobicDocket No.: 4478PCTamine is selected from the group consisting of unsubstituted or substituted alkyl, alkylene, alkynyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, or arylene amines, with or without heteroatoms. Suitable examples of such hydrophobic amines according to the present disclosure include, but are not limited, benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecyl amine, undecylamine, pentadecylamine, 2-methyl-butylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

[0061] In still another non-limiting embodiment of the present disclosure, the hydrophobic moiety includes that of a silicon-based compound. Suitable and non-limiting examples of silicon-based compounds according to the present disclosure include: aminopropyl methylsiloxane–dimethylsiloxane, N-ethylamino isobutyl terminated polydimethyl siloxane, poly(1,1-dimethylsilazane) telomer, aminopropyl terminated polydimethyl siloxane, monoamino propyl terminated polydimethyl siloxane, (tetramethyl piperidinyloxy) propylmethyl siloxane)-dimethylsiloxane copolymer, polydimethyl siloxane, carbinol (hydroxyl) terminated polydimethyl siloxane, monocarbinol terminated polydimethylsiloxane, monocarbinol terminated functional polydimethylsiloxane, [Bis(hydroxyethyl)amine] terminated polydimethylsiloxane, silanol terminated polydimethylsiloxane, silanol terminated polydiphenyl siloxane, dodecylmethyl siloxane-hydroxy polyalkyleneoxy propyl methyl siloxane, and combinations thereof.NH2poly(1,1-dimethylsilazane) telomerDocket No.: 4478PCTmonoaminopropylterminated polydimethylsiloxane (amino siloxane)polydimethylsiloxane

[0062] In one non-limiting embodiment of the present disclosure, the functionalized or unfunctionalized moiety is a hydrophilic moiety selected from those of the group consisting of hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether amine monoalkyl ethers, hydrophilic polyether alcohol monoaryl ethers, hydrophilic polyether amine monoaryl ethers, hydrophilic polyether alcohol monoalkaryl ethers, hydrophilic polyether amine monoalkaryl ethers, and combinations thereof.Docket No.: 4478PCT

[0063] In one non-limiting embodiment of the present disclosure, the hydrophilic moiety is that of a hydrophilic polyether alcohol monoalkyl ether. The hydrophilic polyether alcohol monoalkyl ether is selected from the group consisting of polyethylene glycol monomethyl ethers, polyethylene glycol monoethyl ethers, polypropylene glycol monomethyl ethers, polypropylene glycol monoethyl ethers, poly(ethylene glycol -co-propylene glycol) monomethyl ethers, poly(ethylene glycol-co-propylene glycol) monoethyl ethers, and combinations thereof.

[0064] In still another non-limiting embodiment of the present disclosure, the hydrophilic polyether alcohol monoalkyl ether is polyethylene glycol monomethyl ether. The hydrophilic polyether alcohol monoalkyl ether according to the present disclosure has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons. In another nonlimiting embodiment of the present disclosure, the molecular weight varies in the range from about 2,000 Daltons to about 4,000 Daltons.

[0065] In another non-limiting embodiment of the present disclosure, the hydrophilic moiety is that of a hydrophilic polyether amine monoalkyl ether and polyether amine monoaralkyl ether having one or more structure selected from the following group of structures:wherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

[0066] Commercially available hydrophilic polyether amine monoalkyl ethers may also be used in the present disclosure, such as JEFFAMINE® M-series and XTJ-series amines. Suitable and non-limiting examples of such products include, but are not limited to, JEFFAMINE® M-600, M-1000, M-2005, M-2070, XTJ-435, and XTJ-436 amines, all of which are available from Huntsman Corporation.

[0067] The molar ratio of maleated natural oil to the hydrophilic moiety may vary in the range from about 1: 4 to about 10: 1 and alternatively may vary in the range of from about 1: 3 to aboutDocket No.: 4478PCT1: 1. Similarly, the molar ratio of maleated natural oil to the hydrophobic moiety may vary in the range from about 1: 4 to about 10: 1, and alternatively may vary in the range of from about 1: 3 to about 1: 1.

[0068] Further, the reaction of the maleated natural oil with a hydrophilic moiety, a hydrophobic moiety or a combination thereof may be carried out without special considerations and is known to persons skilled in the related art. However, in one non-limiting embodiment of the present disclosure, the reaction may be carried out at a temperature varying in the range of from about 80 °C to about 150 °C, alternatively in the range of from about 80 °C to about 120 °C, or from about 90 °C to about 150 °C. Further, the reaction may be carried out for a time period varying from about 3 to 14 hours, or from about 8 to 14 hours.

[0069] In one non-limiting embodiment of the present disclosure, the oral solid dosage composition comprises a reaction product of (i) a maleated soybean oil; and (ii) behenyl alcohol or polyethylene glycol monomethyl ether, or a combination thereof. In another non-limiting embodiment of the present disclosure, the oral solid dosage composition comprises a reaction product of: (i) a maleated soybean oil; (ii) behenyl alcohol; and (iii) polyethylene glycol monomethyl ether.

[0070] In one non-limiting embodiment, for illustrative purpose, the reaction product comprises one or more structures selected from the following group of structures:^OMeVOMeDocket No.: 4478PCTwherein n is an integer from about 20 to about 200, or from about 40 to about 100, and Me is methyl.

[0071] The oral solid dosage composition according to the present disclosure comprising reaction product may further comprise an additional moiety. The additional moiety is selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof. The additional hydrophilic and hydrophobic moieties according to the present disclosure may either be identical to or different from the hydrophilic and hydrophobic moieties reacted with the maleated natural oil to form the present reaction product.

[0072] In one non-limiting embodiment of the present disclosure, the additional hydrophilic moiety is selected from those of the group consisting of hydrophilic polyether glycols, hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether polyamines, hydrophilic polyether amine monoalkyl ethers, and combinations thereof.

[0073] In another non-limiting embodiment of the present disclosure, the additional hydrophilic moiety is that of a hydrophilic polyether alcohol monoalkyl ether selected from the group consisting of polyethylene glycol monomethyl ethers, polyethylene glycol monoethyl ethers, polypropylene glycol monomethyl ethers, polypropylene glycol monoethyl ethers, poly(ethylene glycol-co-propylene glycol) monomethyl ethers, poly(ethylene glycol-co-propylene glycol) monoethyl ethers, and combinations thereof.

[0074] In still another non-limiting embodiment of the present disclosure, the additional hydrophilic moiety is that of a hydrophilic polyether glycol selected from the group consisting of polyethylene glycol, polypropylene glycol, poly(ethylene glycol-co-propylene glycol), and combinations thereof.Docket No.: 4478PCT

[0075] In yet another non-limiting embodiment of the present disclosure, the hydrophilic polyether alcohol monoalkyl ether is polyethylene glycol monomethyl ether; and the hydrophilic polyether glycol is polyethylene glycol.

[0076] Further, the hydrophilic polyether alcohol monoalkyl ether or hydrophilic polyether glycol has a weight average molecular weight varying in the range from about 1,000 Daltons to about 6,000 Daltons. In another non-limiting embodiment of the present disclosure, the molecular weight varies in the range from about 2,000 Daltons to about 4,000 Daltons.

[0077] In another non-limiting embodiment of the present disclosure, the additional hydrophilic moiety is that of a hydrophilic polyether amine monoalkyl ether and polyether amine monoaralkyl ether having one or more structure selected from the following group of structures:Me or Etwherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

[0078] Commercially available hydrophilic polyether amine monoalkyl ethers may also be used for the purpose of the present disclosure, such as JEFFAMINE® M-series and XTJ-series amines. Suitable and non-limiting examples of such products include, but are not limited to, JEFFAMINE® M-600, M-1000, M-2005, M-2070, XTJ-435, and XTJ-436 amines, all of which are available from Huntsman Corporation.

[0079] In one non-limiting embodiment of the present disclosure, the additional hydrophobic moiety is selected from the those of the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof.

[0080] In one non-limiting embodiment of the present disclosure, the additional hydrophobic moiety is that of a hydrophobic alcohol which may be a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl alcohol having about 6 to aboutDocket No.: 4478PCT36 carbon atoms. In another non-limiting embodiment of the present disclosure, the hydrophobic alcohols may have about 10 to about 24 carbon atoms. Suitable examples of such hydrophobic alcohols include, but are not limited to, hexanol, heptanol, nonanol, decanol, dodecanol, phenol, ethylbenzyl alcohol, 2-ethyl-l-hexanol, 1-octanol, 2-octanol, 2-butyl-l -octanol, 2-octyl-l -dodecyl alcohol, 1 -tetradecanol, 2-tetradecanol, 1 -hexadecanol, 2-hexadecanol, 1-octadecanol 3,7-dimethyl- 1-octanol, 2-propyl-l -pentanol, 4-methyl-l -pentanol, cetyl alcohol, stearyl alcohol, eicosanol, behenyl alcohol, and combinations thereof. In still another non-limiting embodiment of the present disclosure, the hydrophobic alcohol is behenyl alcohol.

[0081] In another non-limiting embodiment of the present disclosure, the additional hydrophobic moiety is that of a hydrophobic amine. The hydrophobic amine according to the present disclosure may be a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl amine having about 6 to about 36 carbon atoms. In another non-limiting embodiment of the present disclosure, the hydrophobic amine may have from about 10 to about 24 carbon atoms. Suitable and non-limiting examples of such hydrophobic amines include: benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecylamine, undecylamine, pentadecylamine, 2-methyl-butylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

[0082] In still another non-limiting embodiment of the present disclosure, the additional hydrophobic moiety may be that of a silicon-based compound. Suitable and non-limiting examples of silicon-based compound according to the present disclosure include: aminopropylmethylsiloxane-dimethylsiloxane, N-ethylaminoisobutyl terminated poly dimethylsiloxane, poly(1,1-dimethylsilazane) telomer, aminopropyl terminated polydimethylsiloxane, monoaminopropyl terminated polydimethylsiloxane, (tetramethylpiperidinyloxy)propylmethylsiloxane)-dimethylsiloxane copolymer, polydimethylsiloxane, carbinol (hydroxyl) terminated polydimethylsiloxane, monocarbinol terminated poly dimethyl siloxane, monocarbinol terminated functional polydimethylsiloxane, [Bis(hydroxyethyl)amine] terminated polydimethylsiloxane, silanol terminated polydimethylsiloxane, silanol terminated polydiphenylsiloxane, dodecylmethylsiloxane-hydroxypolyalkyleneoxypropyl methylsiloxane, and combinations thereof.Docket No.: 4478PCT

[0083] The oral solid dosage composition according to the present disclosure further comprises at least one ingredient selected from the group consisting of an active pharmaceutical ingredient (API), a filler, a binder, a surfactant, a disintegrating agent, a lubricant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0084] Any active pharmaceutical ingredients (API) which are well known to persons skilled in the related art may suitably be used for the purpose of the present disclosure, for example, drugs, proteins, or peptides including macrocyclic peptides In one non-limiting embodiment of the present disclosure, the active pharmaceutical ingredient may be a drug. Any drugs having a wide range of water solubilities may suitably be used in the present OSD composition. In one nonlimiting embodiment of the present disclosure, the drugs may be BCS class I, BCS class II, BCS class III, or BCS class IV drugs including proteins, peptides, and macrocyclic peptides.

[0085] Suitable and non-limiting examples of BCS class I drug include Diltiazem, Labetalol, Captopril, Enalapril, Metoprolol, Propranolol, Phenylalanine, Antipyrine, Glucose, L-Dopa, Chloroquine, Acetaminophen, Theophylline, and Verapamil. Suitable and non-limiting examples of BCS class II drug include glibenclamide, bicalutamide, ezetimibe, fenofibrate, glipizide, atovaquone, carbamazepine, danazol, griseofulvin, ketoconazole, troglitazone, ibuprofen, nifedipine, nitrofurantoin, phenytoin, sulfamethoxazole, trimethoprim, valproic acid, praziquantel, retinol palmitate, and sulfasalazine. Suitable and non-limiting examples of BCS class III drugs include cimetidine, acyclovir, atenolol, ranitidine, abacavir, captopril, chloramphenicol, codeine, colchicine, dapsone, ergotamine, kanamycin, tobramycin, tigecycline, zanamivir, hydralazine, hydrochlorothiazide, levothyroxine, methyldopa, paracetamol, propylthiouracil, pyridostigmine, sodium cioxacillin, thiamine, benznidazole, diazocine, ethambutol, ethosuximide, folic acid, nicotinamide, nifurtimox, and salbutamol sulfate. Similarly, suitable and non-limiting examples of BCS class IV drugs include hydrochlorothiazide, furosemide, cyclosporin A, itraconazole, indinavir, nelfmavir, ritonavir, saquinavir, nitrofurantoin, albendazole, acetazolamide, and azithromycin.

[0086] Further, pharmaceutical acceptable excipeints which are commonly used in the oral solid dosage compositions may also be used as one of the ingredients of the present OSD composition, for example, excipients as described in Handbook of Pharmaceutical Excipient, Rows et al., Eds.,Docket No.: 4478PCT4th Edition, Pharmaceutical Press (2003) or Remington; The Science and Practice of Pharmacy (formerly called Remington’s Pharmaceutical Sciences), Alfonso R. Gennaro, ed., Lippincott Williams & Wilkins; 20th edition (Dec. 15, 2000). Suitable examples of such ingredients include, but are not limited to, a filler, a binder, a surfactant, a disintegrating agent, a lubricant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0087] The oral solid dosage composition according to the present disclosure comprises at least one filler. A filler is an excipient normally used in solid oral dosage forms to provide sufficient mass and volume. In one non-limiting embodiment of the present disclosure, the filler is selected from the group consisting of monosaccharides, di saccharides, polysaccharides, inorganic acid salts, and combinations thereof. Suitable and non-limiting examples of such fillers are cellulose, lactose, sucrose, sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, calcium sulfate, Bentonite, Kaolin, calcium diphosphate dihydrate and hydrosulfates, microcrystalline cellulose, and combinations thereof.

[0088] The oral solid dosage composition according to the present disclosure further comprises at least one binder selected from the group consisting of polyvinyl pyrrolidone, starch, pregelatinized starch, gum arabic, tragacanth gum, guar gum, pectin, wax-based binders, polyethylene oxide, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and combinations thereof.

[0089] The oral solid dosage composition according to the present disclosure comprises at least one surfactant. The surfactants are typically included in oral solid dosage form to reduce the interfacial energy barrier between the dissolution medium and the API, which will allow for more efficient wettability. The use of surfactants in conventional oral solid dosage forms is well-known to person skilled in the related art. Accordingly, such surfactants may also be used in the present oral solid dosage composition. In one non-limiting embodiment of the present disclosure, surfactant is selected from the group consisting of sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

[0090] The oral solid dosage composition according to the present disclosure further comprises a film forming agent. The film forming agent is selected from the group consisting of celluloseDocket No.: 4478PCTethers, synthetic polymers, sugars, and combinations thereof. Suitable and non-limiting examples of cellulose ethers that can be used in the present OSD composition include, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxy ethyl cellulose (HEC), carboxymethyl cellulose (CMC), and combinations thereof. Similarly, suitable and non-limiting examples of synthetic polymers can include, but are not limited, polyvinylpyrrolidone (PVP), copovidone, polyvinyl alcohol, ethylene glycol and vinyl alcohol graft copolymer, and combinations thereof.

[0091] In another non-limiting embodiment of the present disclosure, the sugar is selected from the group consisting of polydextrose, maltodextrin, sucrose, dextrose, lactose, and combinations thereof.

[0092] The oral solid dosage composition according to the present disclosure comprises a disintegrating agent. In one non-limiting embodiment of the present disclosure, the disintegrating agent is selected from the group consisting of crospovidone, crosscarmellose sodium, low substituted hydroxypropyl cellulose, sodium starch glycolate, and combinations thereof.

[0093] The oral solid dosage composition according to the present disclosure further comprises a lubricant. In one non-limiting embodiment of the present disclosure, the lubricant is selected from the group consisting of calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, palmitic acid, calcium silicate, mineral oils, bees wax, carnauba wax, hydrogenated vegetable oils, glyceryl behenate, sodium stearyl fumarate, and combinations thereof.

[0094] The oral solid dosage composition according to the present disclosure also comprises a colorant. The colorants are primarily used to impart appearance to the pharmaceutical dosage forms. Additionally, colorants may be required to increase the aesthetic appearance, prolong stability of formulations, produce standard preparations, or identify particular formulation. In one non-limiting embodiment of the present disclosure, the colorant may include at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red, yellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.Docket No.: 4478PCT

[0095] The oral solid dosage composition, according to the present disclosure further comprises an anti-tacking agent or a glidant. Several types of anti-caking agents which are known to a person skilled in the related art may suitably be used in the present OSD composition. In one non-limiting embodiment of the present disclosure, the anti-caking agents or the glidant is selected from the group consisting of talc, silica, medium chain triglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof.

[0096] The oral solid dosage composition according to the present disclosure may also comprise at least one plasticizer. The plasticizers are primarily used in oral solid dosage forms as low molecular weight, non-volatile additives. The plasticizer which is known to a person skilled in the related art may suitably be used in the present OSD composition. Suitable examples of such plasticizers include, but are not limited to, (i) polyols such as propylene glycol, glycerol, polyethylene glycols (PEG in particular 200-6000 grades); (ii) water insoluble organic esters such as phthalate esters (e g., dibutyl, diethyl, and dimethyl phthalates), dibutyl sebacate, dibutyl adipate (DBA), acetyltri ethyl citrate (ATEC), acetyltributyl citrate (ATBC), tributyl citrate (TBC); (iii) water miscible organic esters such as citrate esters, glyceryl triacetate; and (iv) oils / glycerides such as castor oil, mineral oil, acetylated monoglycerides, and the like.

[0097] In another non-limiting embodiment of the present disclosure, the oral solid dosage composition may also include flavors or sweeteners, or both. Flavors may be included in some oral solid dosage forms to make them more palatable or to support recognition. Suitable and nonlimiting examples of flavors that may be present in the OSD composition of the present disclosure include natural, artificial, organic flavors or combinations thereof, for example, strawberry, pineapple, blueberry. Grape, lemon, lime, orange, apple, vanilla, and vanillin flavors.

[0098] In another non-limiting embodiment of the present disclosure, the OSD composition comprises at least one sweetener or a sweetening agent. Sweetening agents are chemical substances that are added to either mask the unpleasant taste or enhance the perception of a sweet taste in some oral pharmaceutical preparations such as tablets, syrup, suspension etc. The sweetening agent used in the present OSD composition may be a plant-derived sweetening agent or an artificial sweetening agent. Suitable and non-limiting examples of the plant-derived sweetening agents include, but are not limited to, erythritol, lactitol, maltitol, mannitol, xylitol,Docket No.: 4478PCTand the like. Similarly, suitable and non-limiting examples of artificial sweetening agents include, but are not limited to aspartame, neotame, alitame, and the like.

[0099] It is within the purview of a person having an ordinary skill in the art to determine the appropriate amount of ingredients to be added in the OSD composition. In one non-limiting embodiment of the present disclosure, the reaction product may present in an amount from about 5.0 wt.% to about 70.0 wt.% of the total oral solid dosage composition weight. In another nonlimiting embodiment of the present disclosure, the amount may vary in the range of from about 5.0 wt.% to about 10.0 wt.%>, or from about 10.0 wt. % to about 20.0 wt. %>, or from about 20.0 wt.%> to about 30.0 wt. %, or from about 40.0 wt. % to about 50.0 wt. %, or from about 50.0 wt. % to about 60.0 wt.%o, or from about 60.0 wt.% o about 70.0 wt.%, of the total oral solid dosage composition weight.

[0100] Similarly, the ingredient (including the API) may be present in an amount from about 0.1 wt.% to about 95.0 wt.%> of the total oral solid dosage composition, Alternatively the amount may vary in the range of from about 30.0 wt. % to about 95.0 wt. % of the total OSD composition weight. In another non-limiting embodiment of the present disclosure, the amount of ingredients may vary in the range from about 1.0 wt.% to about 10.0 wt.%>, or about 20.0 wt.% to about 50.0 wt. %>, or from about 40.0 wt.%> to about 65.0 wt.%>, or from about 50.0 wt.° / o to about 75.0 wt. %>, of the total OSD weight.

[0101] Further, the active pharmaceutical ingredient may be present in a pharmaceutical effective amount. The amount of the active pharmaceutical ingredient may be varied depending upon various factors including, but not limiting to, type of drug or drugs being used, nature and severity of the ailment being treated / cured, the type and content of active ingredients or other ingredients contained in the pharmaceutical composition, dosage form, patient’s age, weight, health condition and eating behavior, drug adminstration time, and the like. The amount of active pharmaceutical ingredient according to the present disclosure may vary in the range of from about 1.0 wt. %o to about 70.0 wt. %>, of the total oral solid dosage composition weight. In one non-limiting embodiment of the present disclosure, the amount of active pharmaceutical ingredient may vary in the range from about 1.0 wt. % to about 10.0 wt.%, or from about 10.0 wt.% to about 20.0 wt. %, or from about 20.0 wt. % to about 30.0 wt. % or from about 30.0 wt. % to about 40.0 wt. %, or fromDocket No.: 4478PCTabout 40.0 wt.% to about 50.0 wt.%, or from about 50.0 wt.% to about 60.0 wt.%, or from about 60.0 wt.% to about 70.0 wt.%, of the total oral solid dosage composition weight.

[0102] Further, the oral solid dosage composition according to present disclosure may be present in various forms, including but not limiting to, tablets, minitablets, capsules, powder, granules, multi particulates, lozenges, and candies. Further, the oral solid dosage composition according to the present disclosure is a coated oral solid dosage composition. In one non-limiting embodiment of the present disclosure, the oral solid dosage composition is a tablet, alternatively a coated tablet.

[0103] The oral solid dosage composition according to the present disclosure may be a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition. In one non-limiting embodiment of the present disclosure, the oral solid dosage composition is a coated pharmaceutical composition. In still another non-limiting embodiment of the present disclosure, the coated pharmaceutical composition is a coated tablet.

[0104] Further, the oral solid dosage composition according to the present disclosure may be a dry film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition.

[0105] In another aspect, the present disclosure provides a granule composition comprising: (i) the reaction product of the present disclosure. The granule composition according to the present disclosure may be used as a dry, wet or a melt binder or a binding agent in the oral solid dosage composition of the present disclosure.

[0106] The granule composition according to the present disclosure further comprises at least one active pharmaceutical ingredient. Any active pharmaceutical ingredients (API) which are well known to persons skilled in the related art may suitably be used for the purpose of the present disclosure, for example, drugs, proteins, or peptides including macrocyclic peptides In one nonlimiting embodiment of the present disclosure, the active pharmaceutical ingredient may be a drug. Any drugs having a wide range of water solubilities may suitably be used in the present OSD composition. In one non-limiting embodiment of the present disclosure, the drugs may be BCS class I, BCS class II, BCS class III, or BCS class IV drugs including proteins, peptides, and macrocyclic peptides, as herein above described in the present disclosure.Docket No.: 4478PCT

[0107] The reaction product may be present in an amount varying in the range of from about 5.0 wt.% to about 20.0 wt.% of the total granule composition weight. In another non-limiting embodiment of the present disclosure, the amount may vary in the range from about 5.0 wt.% to about 6.0 wt.%, or from about 6.0 wt.% to about 7.0 wt.%, or from about 7.0 wt.% to about 8.0 wt. %, or from about 8.0 wt.% to about 9.0 wt. %, or from about 9.0 wt.% to about 10.0 wt.%, or from about 10.0 wt.% to about 11.0 wt.%, or from about 11.0 wt.% to about 12.0 wt.%, or from about 13.0 wt.% to about 14.0 wt.%, or from about 14.0 wt.% to about 15.0 wt.%, or from about 15.0 wt.% to about 16.0 wt.%, or from about 16.0 wt.% to about 17.0 wt.%, or from about 17.0 wt. % to about 18.0 wt. %, or from about 18.0 wt. % to about 19.0 wt. %, or from about 19.0 wt. % to about 20.0 wt.% of the total granule composition weight.

[0108] Similarly, the active pharmaceutical ingredient may be present in an amount varying in the range from about 80.0 wt.% to about 95.0 wt.% of the total granule composition weight. Alternatively, the amount may vary in the range from about 80.0 wt. % to about 85.0 wt. %, or from about 85.0 wt. % to about 90.0 wt.%, or from about 90.0 wt.% to about 95.0 wt. % of the total granule composition weight.

[0109] In still another aspect, the present disclosure provides an oral solid dosage composition comprising the (i) the granule composition according to the present disclosure; and (ii) at least one additional ingredient.

[0110] In one non-limiting embodiment of the present disclosure, the ingredients are selected from the group consisting of a filler, an additional binder, a surfactant, a disintegrating agent, a lubricant, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0111] The oral solid dosage composition according to the present disclosure that comprises the present granule composition as a binder, or a binding agent may further comprise additional binders. Suitable examples of such additional binder include, but are not limited to, polyvinyl pyrrolidone, starch, pre-gelatinized starch, gum arabic, tragacanth gum, guar gum, pectin, waxbased binders, polyethylene oxide, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and combinations thereof.Docket No.: 4478PCT

[0112] It is within the purview of a person ordinary skilled in the art to determine the appropriate amount of ingredients to be added in the oral solid dosage composition. In one nonlimiting embodiment of the present disclosure, the granule composition may be present in an amount from about 5.0 wt. % to about 90.0 wt. % of the total oral solid dosage composition weight.

[0113] In another non-limiting embodiment of the present disclosure, the amount may vary in the range from about 5.0 wt.% to about 10.0 wt.%, or from about 10.0 wt.% to about 20.0 wt.%, or from about 20.0 wt.% to about 30.0 wt.%, or from about 30.0 wt.% to about 40.0 wt.%, or from about 40.0 wt.% to about 50.0 wt.%, or from about 50.0 wt.% to about 60.0 wt. %>, or from about 60.0 wt.% to about 70.0 wt. %>, or from about 70.0 wt. % to about 80.0 wt. %o, or from about 80.0 wt. % to about 90.0 wt.%, of the total oral solid dosage composition weight.

[0114] Similarly, the ingredient may be present in an amount from about 10.0 wt.% to about 50.0 wt.% of the total oral solid dosage composition weight. Alternatively, the amount may vary in the range from about 10.0 wt.% to about 20.0 wt. %>, or from about 20.0 wt. %> to about 30.0 wt. %>, or from about 30.0 wt.% to about 40.0 wt.%, or from about 40.0 wt.% to about 50.0 wt.%, of the total oral solid dosage composition weight.

[0115] In another aspect, the present disclosure provides a coating composition suitable for coating an oral solid dosage form. The coating composition according to the present disclosure comprises the reaction product of (i) maleated natural oils; and (ii) at least one functionalized and unfunctionalized moiety selected from the group consisting of hydrophobic moiety, hydrophilic moiety, and combinations thereof, according to the present disclosure.

[0116] The coating composition according to the present disclosure further comprises at least one ingredient selected from the group consisting of a surfactant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0117] The coating composition according to the present disclosure comprises at least one surfactant. The surfactants are used in the coating compositions to enhance drug release, solubility, and wettability. Additionally, they serve as emulsifiers, dispersants, and solubilizers in oral solid dosage forms. Surfactants which are known to persons skilled in the art may suitably be used for the purpose of the present disclosure. Suitable and non-limiting examples of such surfactantsDocket No.: 4478PCTinclude, but are not limited to, sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

[0118] The coating composition, according to the present disclosure, further comprises a film forming agent. The film forming agents are typically used to provide mechanical strength to the coatings. In one non-limiting embodiment of the present disclosure, the film forming agent is selected from the group consisting of cellulose ethers, synthetic polymers, sugars, and combinations thereof. Suitable and non-limiting examples of cellulose ethers include; hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), carboxymethyl cellulose (CMC), and combinations thereof. Similarly, suitable and nonlimiting examples of synthetic polymers include: polyvinylpyrrolidone (PVP), copovidone, polyvinyl alcohol, ethylene glycol and vinyl alcohol graft copolymer, and combinations thereof. In another non-limiting embodiment of the present disclosure, the sugar is selected from the group consisting of polydextrose, maltodextrin, sucrose, dextrose, lactose, and combinations thereof.

[0119] The coating composition according to the present disclosure also comprises a colorant. The colorants are primarily used to impart appearance to the pharmaceutical dosage forms. Additionally, colorings may be required to increase the aesthetic appearance, prolong stability of formulations, produce standard preparations, or identify particular formulation. In one nonlimiting embodiment of the present disclosure, the colorant may include at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red, yellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.

[0120] The coating composition according to the present disclosure further comprises an antitacking agent or a glidant. Anti-tacking agents are typically used to reduce the stickiness of the coating material. Anti-tacking agents are typically non-volatile and water-insoluble compounds that, when added to the coating compositions, provide a lubricating effect on the solid dosage forms. Several types of anti-caking agents which are known to persons skilled in the related art may suitably be used in the present coating composition. Suitable and non-limiting examples ofDocket No.: 4478PCTsuch anti-caking agents or the glidant include talc, silica, medium chain triglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof.

[0121] The coating composition according to the present disclosure may also comprise at least one plasticizer. The plasticizers are primarily used in oral solid dosage forms as low molecular weight, non-volatile additives. They are used to reduce the glass transition temperature (Tg) and increase flexibility to avoid cracking and subsequent peel-off of polymer films. The plasticizers which are known to persons skilled in the related art may suitably be used in the present coating composition. Suitable and non-limiting examples of such plasticizers include: (i) polyols such as propylene glycol, glycerol, polyethylene glycols (PEG in particular 200-6000 grades); (ii) water insoluble organic esters such as phthalate esters (e g., dibutyl, diethyl, and dimethyl phthalates), dibutyl sebacate, dibutyl adipate (DBA), acetyltriethyl citrate (ATEC), acetyltributyl citrate (ATBC), tributyl citrate (TBC); (iii) water miscible organic esters such as citrate esters, glyceryl triacetate; and (iv) oils / glycerides such as castor oil, mineral oil, acetylated monoglycerides, and the like.

[0122] In another non-limiting embodiment of the present disclosure, the coating composition may also include flavors or sweeteners, or both. Flavors may be included in some oral solid dosage forms to make them more palatable or to support recognition. Suitable and non-limiting examples of such flavors include natural, artificial, organic flavors or combinations thereof, for example, strawberry, pineapple, blueberry, grape, lemon, lime, orange, apple, vanilla, and vanillin flavors.

[0123] In another non-limiting embodiment of the present disclosure, the coating composition comprises at least one sweetener or a sweetening agent. Sweetening agents are chemical substances that are added to either mask the unpleasant taste or enhance the perception of a sweet taste in some oral pharmaceutical preparations such as tablets, syrup, suspension etc. The sweetening agent used in the present coating composition may be a plant-derived sweetening agent or an artificial sweetening agent. Suitable and non-limiting examples of the plant-derived sweetening agents include: erythritol, lactitol, maltitol, mannitol, xylitol, and the like. Similarly, suitable and non-limiting examples of artificial sweetening agents include: aspartame, neotame, alitame, and the like.Docket No.: 4478PCT

[0124] It is within the purview of a person who is ordinary skilled in the art to determine the appropriate amount of ingredients to be added to the coating compositions, which can vary widely depending on the objectives to be achieved. In one non-limiting embodiment of the present disclosure, the ingredients (in total) may be present in amount from about 30.0 wt.% to about 95.0 wt. % of the total dry weight of the coating composition. In another non-limiting embodiment of the present disclosure, the amount of ingredients may vary in the range of from about 30.0 wt.% to about 45.0 wt. %, or from about 40.0 wt. %> to about 50.0 wt. %>, or from about 50,0 wt. %> to about 60.0 wt.%, or from about 60.0 wt. % to about 70.0 wt.%, or from about 70.0 wt.% to about 80.0 wt.%, or from about 80.0 wt.% to about 90.0 wt.%, or from about 90.0 wt.% to the 95.0 wt.% of the total dry weight of the coating composition.

[0125] Similarly, the reaction product may be present in an amount from about 5.0 wt.% to about 70.0 wt.% of the total dry weight of the coating composition. In another non-limiting embodiment of the present disclosure, the amount may vary in the range of from about 5.0 wt.%> to about 10.0 wt. %>, or from about 10.0 wt. % to about 20.0 wt. %, or from about 20.0 wt. % to about 30.0 wt.%>, or from about 30.0 wt.%> to about 40.0 wt.%>, or from about 40.0 wt. % to about 50.0 wt. %>, or from about 50.0 wt.%> to about 60.0 wt.%>, or from about 60.0 wt.%> to about 70.0 wt. / o, of the total dry weight of the coating composition.

[0126] Further, the coating composition according to the present disclosure may be present in dry powder form. Alternatively, the present coating composition may be present in the form of a solid phase of a solvent suspension with a solid content from about 15.0 % to about 60.0 % by weight. In one non-limiting embodiment of the present disclosure, the solvent suspension includes the present coating composition suspended in at least one solvent. Further the solvent may be an s an aqueous solvent, an organic solvent, or combinations thereof.

[0127] Further, the coating composition according to the present disclosure may be applied to a wide range of oral solid dosage form, such as tablets, minitablets, multi particulates, powders, granules, tablets lozenges, and candies. In non-limiting embodiment of the present disclosure, the coating composition is applied to tablets.

[0128] In another aspect, the present disclosure provides a coating composition for pharmaceutical tablets comprising: (i) the reaction product of the present disclosure; and (ii) at least one ingredient selected from the group consisting of a surfactant, a film forming agent, aDocket No.: 4478PCTplasticizer, a colorant, an anti-tacking agent, a glidant, a plasticizer, a sweetener, and combinations thereof.

[0129] Methods for preparing the coating compositions, such as dry powder blends is well known to a person skilled in the related art. Accordingly, these conventional methods may be used for preparing the present coating composition. In one non-limiting embodiment of the present disclosure, the coating composition is prepared by dry blending the present reaction product and at least one ingredient as herein above described in the present disclosure. The blending may be carried out using a commercial-grade mixer such as high-shear mixers of the design manufactured by Littleford Day, Inc. If it is advantageous to use liquid ingredients, such as triethyl citrate as plasticizer, then they can be sprayed into and during the dry blending of the powdered materials.

[0130] As stated herein above in the present disclosure, the coating composition according to the present disclosure may be applied to a wide range of oral solid dosage forms, such as tablets, minitablets, multi particulates, powders, granules, lozenges, candies and the like. In one nonlimiting embodiment of the present disclosure, the coating composition is used for coating the tablets.

[0131] In one aspect, the present disclosure provides a method for coating oral solid dosage forms. Methods for coating oral solid dosage forms, particularly tablets, are well known to person skilled in the art. Accordingly, these conventional methods may also be suitably used for coating the oral solid dosage forms with the present coating composition. Suitable and non-limiting examples of such methods include hot melt extrusion coating, film coating, compression coating and the like.

[0132] In one non-limiting embodiment of the present disclosure, the method for coating oral solid dosage forms includes a hot-melt extrusion coating. In this method, the coating composition is applied on oral solid dosage forms in a molten state.

[0133] In one non-limiting embodiment of the present disclosure, the method comprises the following steps: (i) mixing the active pharmaceutical ingredient and the reaction product of the present disclosure; (ii) blending the obtained physical mixture in a Turbula mixer; (iii) heating the blend obtained from the method step (ii) in a hot-melt extruder at least up to the softening point of the present reaction product; (iii) extruding the thus heated blend to obtain hot melt extrudates or granules; (iv) milling and sieving the hot melt extrudates or granules to obtain hot melt extrudedDocket No.: 4478PCTmilled granules; (iv) blending at least one ingredient of the coating composition as hereinabove described to obtain a formulation blend; and (v) compressing the formulation blend to obtain hot melt coated tablets.

[0134] The mixing in the method step (i) may be carried out in a mixer known to person skilled in the related art. The mixer may be a roll mixer, a shaking mixer, a shear mixer, or a compulsory mixer. The blend which has been heated in the extruder at least up to the softening point of the present reaction product is extruded from the extruder through a die with at least one bore. The process according to the present disclosure requires the use of suitable hot melt extruders, preferably screw extruders. Screw extruders which are equipped with two screws (twin-screwextruders) are particularly preferred. Further, the hot melt coating extrusion coating according to the present disclosure may be carried out in a bottom spray or a tangential spray fluid bed coater.

[0135] In another non-limiting embodiment of the present disclosure, the method for coating oral solid dosage forms includes a film coating method. Film coating techniques are widely used for coating oral solid dosages forms. In this technique, a thin and uniform layer of polymer-based formulations are deposited onto the surface of oral solid dosage forms. The method for coting oral dosages forms according to present disclosure comprises the following steps: (i) preparing a coating suspension comprising the present coating composition; (ii) forming a layer on a solid dosage by applying the coating suspension; and (iii) drying the layer on the solid dosage to obtain oral solid dosage form coated with the present coating composition.

[0136] In one non-limiting embodiment of the present disclosure, the present coating composition is mixed in a solvent to obtain the coating suspension. The mixing is typically carried out using an overhead stirrer and for a time period sufficient to obtain the homogenous coating suspension. The solvent according to the method of the present disclosure can be an aqueous solvent or an organic solvent. In one non-limiting embodiment of the present disclosure, the solvent is an aqueous solvent that typically includes water. In another non-limiting embodiment of the present disclosure, the solvent is an organic solvent. Suitable and non-limiting examples of such organic solvents include ethanol, isopropyl alcohol, methanol, acetone, dichloromethane or combinations thereof, Further, the coating suspension is prepared with a total solid content varying the range of from about 5.0 % to 60. 0% w / w.Docket No.: 4478PCT

[0137] Subsequently, the coating suspension is applied onto surface of an oral solid dosage form. The coating suspension may be applied by using a fluid bed coater or a pan coater. In one non-limiting embodiment of the present disclosure, the coating suspension is applied by using a pan coater. Any conventional panning equipment may be used. In one non-limiting embodiment of the present disclosure, a Vector LDCS fitted with a 2.5L fully perforated pan operating under the following conditions: Pan loading, kg: 2.0; Pan speed, rpm: 23 -25; Process air volume, m3 / h: 60.0; Inlet air temperature, °C: 58.0 - 65.0; Product temperature, °C: 38.0 - 43.0; Exhaust air temperature, °C: 43.0 - 48.0; Atomizing air pressure, bar: 20.0 - 22.0; Pattern air pressure, bar: 22.0 - 24.0; and Spray rate, g / min: 5.0, is used. In this method, the oral solid dosage forms are loaded in the pan coater and subsequently, the coating suspension is sprayed onto the surface of oral solid dosage forms. The coated oral solid dosage form thus obtained is then dried to evaporate the solvent, leaving a thin and uniform film or coating of the present coating composition on the surface of the oral solid dosage form. The present coating compositions provide attributes that encompass improved coating adhesion, smoother tablets, enhanced color stability, and better processability.

[0138] The present inventors have surprisingly developed an ultra-high solids coating composition comprising the reaction product of (i) maleated natural oil; and (ii) at least one hydrophilic or hydrophobic moieties or combination of both. This coating composition replaces the polymers and plasticizers typically present in traditional film coating systems, thus enabling high solids concentrations in the present coating composition.Docket No.: 4478PCTEXAMPLES

[0139] Further, certain aspects of the present disclosure are illustrated in detail by way of the following examples. The examples are given herein for illustration of the application and are not intended to be limiting thereof.

[0140] Example A: Grafting of Maleic Anhydride onto Natural Oils

[0141] Example Al: Grafting of Maleic Anhydride onto Soybean Oil

[0142] A 1-L, 4-neck kettle equipped with a thermocouple, condenser, nitrogen sparge adapter, and mechanical stirrer was charged with 600 g of soybean oil (SBO) and 204 g (3 mole equivalents based on SBO) of maleic anhydride. The mixture was sparged at room temperature with nitrogen for 15 minutes, heated slowly from room temperature to 210 °C and then held at 210 °C for 6-8 hours. Completion of the reaction was indicated by NMR, and LC indicated <0.5% of residual maleic anhydride.

[0143] Example A2: Grafting of Maleic Anhydride onto Palm Oil

[0144] A 1-L, 4-neck kettle equipped with a thermocouple, condenser, nitrogen sparge adapter, and mechanical stirrer was charged with 100 g of palm oil and 23 g (2 mole equivalents based on palm oil) of maleic anhydride. The mixture was sparged at room temperature with nitrogen for 15 minutes, heated slowly from room temperature to 210 °C and then held at 210 °C for 8-10 hours. The amber, viscous product was characterized by NMR, and LC indicated <1% of residual maleic anhydride. Yield was >96%.

[0145] Example A3: Grafting of Maleic Anhydride onto Canola Oil

[0146] A 1-L, 4-neck kettle equipped with a thermocouple, condenser, nitrogen sparge adapter, and mechanical stirrer was charged with 100 g of canola oil and 22.2 g (2 mole equivalents based on canola oil) of maleic anhydride. The mixture was sparged at room temperature with nitrogen for 15 minutes, heated slowly from room temperature to 210 °C and then held at 210 °C for 8-10 hours. The amber, viscous product was characterized by NMR, and LC indicated <1% of residual maleic anhydride. Yield was >96%.

[0147] Example A4: Grafting of Maleic Anhydride onto Sunflower OilDocket No.: 4478PCT

[0148] A 1 -L, 4-neck kettle equipped with a thermocouple, condenser, nitrogen sparge adapter, and mechanical stirrer was charged with 100 g of sunflower oil and 22.4 g (2 mole equivalents based on sunflower oil) of maleic anhydride. The mixture was sparged at room temperature with nitrogen for 15 minutes, heated slowly from room temperature to 210 °C and then held at 210 °C for 8-10 hours. The amber, viscous product was characterized by NMR, and LC indicated <1% of residual maleic anhydride. Yield was >96%.

[0149] Example A5: Grafting of Maleic Anhydride onto Castor Oil

[0150] A 1-L, 4-neck kettle equipped with a thermocouple, condenser, nitrogen sparge adapter, and mechanical stirrer was charged with 100 g of castor oil and 21 g (2 mole equivalents based on castor oil) of maleic anhydride. The mixture was sparged at room temperature with nitrogen for 15 minutes, heated slowly from room temperature to 210 °C and then held at 210 °C for 8- 10 hours. The amber, viscous product was characterized by NMR, and LC indicated <1% of residual maleic anhydride. Yield was >96%.

[0151] Example B: Grafting of Hydrophobic and Hydrophilic alcohols onto Maleated Soybean Oil (MSBO) of Example Al

[0152] Example Bl:

[0153] 50.20 g (43.5 mmol) of MSBO, 347.84 g (87.0 mmol) of mPEG-4000, and 8.52 g (26.1 mmol) of behenyl alcohol were mixed in a reaction vessel. The vessel was sealed and maintained under a nitrogen atmosphere. The reaction mixture was stirred and heated at 90 °C for 8 hours, then cooled to 80 °C before discharging from the reaction vessel. A yellow solid reaction product was obtained.

[0154] Example B7:

[0155] 71.87 g (62.2 mmol) of MSBO, 497.99 g (124.5 mmol) of mPEG-4000, and 12.20 g (37.3 mmol) of behenyl alcohol were combined and reacted for 14 hours at 145 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0156] Example B8:

[0157] 104.72 g (90.7 mmol) of MSBO, 217.68 g (54.4 mmol) of mPEG-4000, and 11.85 g (36.3 mmol) of behenyl alcohol were combined and reacted for 14 hours at 145 °C following theDocket No.: 4478PCTexperimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product. mPEG was fully attached to MSBO.CH3(CH2)20CH2OH H3C(O⌢)nOH (behenyl alcohol)0' 1 equiv 0.6-2.6 equivm 50 °cDocket No.: 4478PCT

[0158] Example B9:

[0159] 78.90 g (68.3 mmol) of MSBO and 300.68 g (75.2 mmol) of mPEG-4000 were combined in a reaction vessel, which was then sealed and maintained under a nitrogen atmosphere. The reaction mixture was stirred and heated at 145 °C for 3 hours. Subsequently, 8.93 g (27.3 mmol) of behenyl alcohol was added to the reaction mixture. The reaction was continued at 145 °C for an additional 14 hours under continuous stirring. After completion, the mixture was cooled to 80 °C before being discharged from the reaction vessel. A dark yellow solid was obtained as the reaction product.

[0160] Example B10:

[0161] 77.35 g (67.0 mmol) of MSBO, 294.78 g (73.7 mmol) of mPEG-4000, and 13.13 g (40.2 mmol) of behenyl alcohol were combined and reacted at 145 °C using the experimental procedure of Example B9. After addition of behenyl alcohol, the reaction continued for an additional 14 hours under continuous stirring. A dark yellow solid reaction product was obtained.

[0162] Example Bll:

[0163] 81.10 g (70.2 mmol) of MSBO, 224.78 g (56.2 mmol) of mPEG-4000, and 13.77 g (42.1 mmol) of behenyl alcohol were combined and reacted at 145 °C using the experimental procedure of Example B9. After addition of behenyl alcohol, the reaction continued at 145 °C for additional 14 hours. A dark yellow solid reaction product was obtained.

[0164] Example B12:

[0165] 103.71 g (89.8 mmol) of MSBO, 215.58 g (53.9 mmol) of mPEG-4000, and 17.60 g, (53.9 mmol) of behenyl alcohol were mixed and reacted at 145 °C using the experimental procedure of Example B9. After addition of behenyl alcohol, the reaction mixture was heated for 14 hours. The product was dark yellow solid.

[0166] Example B13:

[0167] 277.16 g (69.3 mmol) of mPEG-4000 was charged in a reaction vessel, which was then sealed and maintained under nitrogen atmosphere. The mPEG-4000 was stirred and heated to 110 °C, followed by drying in vacuo for 2 hours. Subsequently, 40.00 g (34.6 mmol) of MSBO was added to the reaction vessel. The resulting reaction mixture was continuously stirred and reacted at 110 °C for 3 hours. Afterwards, 6.79 g (20.8 mmol) of behenyl alcohol was added, and theDocket No.: 4478PCTreaction was further stirred at the same temperature of 110 °C for an additional 8 hours. The reaction vessel was then cooled to 80 °C before being discharged. A yellow solid reaction product was obtained.Docket No.: 4478PCT

[0168] Example B14:

[0169] 50.00 g (43.3 mmol) of MSBO, 346.45 g (86.6 mmol) of mPEG-4000, and 8.49 g (26.0 mmol) of behenyl alcohol were reacted using the experimental procedure 3, except the reaction was carried out at 115 °C and instead of using MSBO in neat, a 50.0 wt.% solution of MSBO in toluene was used. After the addition of behenyl alcohol, the reaction mixture continued to react at 115 °C for an additional 8 hours. A yellow solid reaction product was obtained.

[0170] Example B15:

[0171] 41.75 g (36.2 mmol) ofMSBO, 289.29 g (72.3 mmol) of mPEG-4000, and 7.09 g (21.7 mmol) behenyl alcohol were reacted using the experimental procedure Example Bl 3, except the reaction was carried out at 145 °C. After the addition of behenyl alcohol, the reaction mixture was continued at 145 °C for an additional 8 hours. A yellow solid reaction product was obtained.

[0172] Example B16:

[0173] 31.00 g (26.8 mmol) ofMSBO, 301.26 g (53.7 mmol) of mPEG-5300, and 5.26 g (16.1 mmol) of behenyl alcohol were combined and reacted for 8 hours at 90 °C using the experimentalDocket No.: 4478PCTprocedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0174] Example B17:

[0175] 40.54 g (35.1 mmol) of MSBO, 279.71 g (49.9 mmol) of mPEG-5300, and 6.88 g (21.1 mmol) of behenyl alcohol were combined and reacted for 8 hours at 90 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0176] Example B18:

[0177] 353.00 g (305.7 mmol) of MSBO, 3377.01 g (611.5 mmol) of mPEG-5300, 59.92 g (183.4 mmol) of behenyl alcohol, and 33.44 g of water were combined and reacted for 8 hours at 90 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0178] Example B19:

[0179] 62.30 g (54.0 mmol) of MSBO, 323.76 g (107.9 mmol) of mPEG-3000, 10.57 g (32.4 mmol) of behenyl alcohol, and 28.70 g of water were combined and reacted for 8 hours at 90 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0180] Example B20:

[0181] 61.70 g (53.4 mmol) of MSBO, 240.48 g (80.2 mmol) of mPEG-3000, and 5.24 g (16.0 mmol) of behenyl alcohol were combined and reacted for 8 hours at 145 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0182] Example B21:

[0183] 51.65 g (44.7 mmol) of MSBO, 313.15 g (89.5 mmol) of mPEG-3500, and 8.77 g (26.8 mmol) of behenyl alcohol were combined and reacted for 8 hours at 90 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0184] Example B22:

[0185] 62.45 g (54.1 mmol) of MSBO and 243.40 g (81.1 mmol) of mPEG-3000 were mixed and reacted for 8 hours at 145 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.Docket No.: 4478PCT

[0186] Example B23:

[0187] 61.58 g (53.3 mmol) ofMSBO and 320.02 g (106.7 mmol) of mPEG-3000 were mixed and reacted for 14 hours at 145 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0188] Example B24:42.52 g (36.8 mmol) of MSBO and 287.26 g (95.8 mmol) of mPEG-3000 were mixed and reacted for 8 hours at 145 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.

[0189] Grafting of Hydrophilic alcohols onto Maleated Soybean Oil (MSBO) of Example Al

[0190] Example B2:

[0191] 82.62 g (71.6 mmol) ofMSBO and 372.11 g (186.1 mmol) of mPEG were mixed and reacted at 90 °C for 8 hours using the experimental procedure of Example Bl. A yellow solid reaction product was obtained.

[0192] Example B3:

[0193] 212.98 g (184.5 mmol) of MSBO and 479.61 g (479.6 mmol) of mPEG-1000 were mixed and reacted at 90 °C for 8 hours using the experimental procedure of Example Bl. An orange solid reaction product was obtained.

[0194] Example B4:

[0195] 114.06 g (98.8 mmol) ofMSBO and 217.34 g (108.7 mmol) of mPEG-2000 were mixed and reacted for 8 hours at 145 °C using the experimental procedure of Example Bl. A dark yellow solid reaction product was obtained. mPEG was fully attached to MSBO.

[0196] Example B5:

[0197] 92.54 g (80.2 mmol) ofMSBO and 352.67 g (88.2 mmol) of mPEG-4000 were mixed and reacted for 14 hours at 145 °C using the experimental procedure of Example Bl. A yellow solid reaction product was obtained.

[0198] Example B6:Docket No.: 4478PCT

[0199] 49.61 g (43.0 mmol) of MSBO and 343.75 g (85.9 mmol) of mPEG-4000 were mixed and reacted for 14 hours at 145 °C using the experimental procedure of Example Bl. This process resulted in the formation of a yellow solid reaction product.TABLE 1. Reaction Products and Their Molecular Weight DataExample Nos. Reaction Products Mn (Da); Mw (Da); Mw / Mn B1 MSBO–2.0mPEG-4000–0.6behenyl alcohol 4245; 11827; 2.79B2 MSBO–2.6mPEG-2000 2513; 7494; 2.98B3 MSBO-2.6mPEG-1000 1841; 4699; 2.55B4 MSBO-l.lmPEG-2000 2340; 10220; 4.37B5 MSBO-l.lmPEG-4000 2451; 13457; 5.49B6 MSBO-2.0mPEG-4000 4621;16152; 3.50B7 MSBO-2.0mPEG-4000-0.6behenyl alcohol 4188; 12610; 3.01B8 MSBO-0.6mPEG-4000-0.4behenyl alcohol 2239; 11391; 5.09B9 MSBO-l.lmPEG-4000-0.4behenyl alcohol 3233; 14346; 4.44B10 MSBO-l.lmPEG-4000-0.6behenyl alcohol 3227; 13395; 4.15B11 MSBO-0.8mPEG-4000-0.6behenyl alcohol 2919; 12808; 4.39B12 MSBO-0.6mPEG-4000-0.6behenyl alcohol 2558; 12298; 4.81B13 MSBO-2.0mPEG-4000-0.6behenyl alcohol 3619; 10694; 2.96B14 MSBO-2.0mPEG-4000-0.6behenyl alcohol 4513; 16389; 3.63B15 MSBO-2.0mPEG-4000-0.6behenyl alcohol 3598; 12806; 3.60B16MSBO-2.0mPEG-5300-0.6behenyl alcohol 7383; 19693; 2.66B 17MSBO-1.4mPEG-5300-0.6behenyl alcohol 7546; 23869; 3.16B 18MSBO-2.0mPEG-5300-0.6behenyl alcohol 6660; 31038; 4.66B 19MSBO-2.0mPEG-3000-0.6behenyl alcohol 5586; 13812; 2.47B20MSBO-1.5mPEG-3000-0.3behenyl alcohol 5109; 14362; 2.81B21MSBO-2.0mPEG-3500-0.6behenyl alcohol 7038; 28468; 4.04B22MSBO-1.5mPEG-3000 3845; 14612; 3.80B23MSBO-2.0mPEG-3000 4857; 15657; 3.22B24MSBO-2.6mPEG-3000 4856; 12409; 2.56Docket No.: 4478PCT

[0200] The reaction products obtained from the examples B1-B24 were characterized by 1H and 13C NMR (in CDC13) and FT-IR. Molar mass of the products was determined by SEC with a refractive index detector in chloroform.

[0201] Approximately 10 g of each reaction products of Example B1-B24 was taken in a 20 mL glass vial individually. This vial was placed in the stability chamber (Caron Scientific) as open dish and exposed to accelerated stability conditions (40°C / 75% relative humidity) for 2 weeks. After two weeks, the material is analyzed to determine the molecular weight and polymer chemistry changes.

[0202] Examples 1-24 (Ex.l-Ex.24): Tablet Coating by Using Coating Suspension

[0203] The reaction products of Examples B1-B24 were used further for preparing coating compositions useful for coating tablets. For this, a coating composition in the form of a suspension was prepared. For this, a required amount of purified water was transferred into a beaker. The various ingredients of the coating composition, including the reaction product of Examples Bl-B24, were weighed according to the proportions specified in Table-2 and 2A. Each ingredient was then added to the purified water in the beaker under continuous stirring using an overhead stirrer. The stirring continued for 45 minutes to ensure uniform dispersion of all the coating ingredients. The spindle (62, 63, or 64) and stirring speed (30rpm) were selected to fall within the normal operating torque range of the viscometer (10% - 90 %). The coating suspension was prepared with 50 % total solids (except for examples 2 and 3). This coating suspension was then applied onto 2 Kg placebo tablets in a Vector LDCS fitted with a 2.5 L as per the operating conditions shown in Table 3. The finished coated tablets thus obtained were subjected to various measurements, including color variability, gloss, surface roughness, and moisture uptake. The observations are listed in Table 4.

[0204] Coating suspension viscosity measurement

[0205] The coating suspensions were prepared at various solid concentrations between 5% to 35% for PVA-based coatings, 5% to 50% for copovidone-HPC-based coatings, and 5% to 60% for coating composition of Examples 1-24. The suspensions were mixed for 45 minutes using an overhead stirrer and the viscosity was measured at 25°C using Brookfield Viscometer.

[0206] Color VariabilityDocket No.: 4478PCT

[0207] The color variability of the finished-coated tablets was measured to ensure consistent and accurate color homogeneity. A standard was created by taking the average of 3 tablets’ color data using the spectrophotometer (Datacolor Spectro 1000). Then, 15 individual tablets were randomly selected, and the color was measured spectrally. The color difference (CMC DE) between each tablet and the standard is generated. The average and standard deviation of the color difference (CMC DE) of 15 tablets were calculated. The results indicate good color homogeneity in a batch as the values are considerably low.

[0208] Gloss

[0209] The finished-coated tablet’s gloss was measured to evaluate the surface quality and coating uniformity as a quality control measure. 50 tablets were randomly selected and arranged on a level black sample tray of the gloss meter (Model 805A Surface Analysis System, Tricor Systems Inc.), such that the plain face of each tablet is upright, and the tablets are tightly packed. The gloss was measured for these tablets, and the average gloss value was calculated. A value greater than 80 gu indicates better gloss, whereas a matte finish surface if the value is less than 30 gu.

[0210] Surface Roughness

[0211] The finished-coated tablet surface is scanned to evaluate the coating height differences.16 tablets were randomly selected and tested for surface roughness using NANOVEA PS50 with a 110 μm optical pen. The Professional 3D 8.3 software is used for data processing to get the surface roughness (sq μm) values. Less than 8 sq μm can be considered a smooth tablet surface.

[0212] Moisture uptake

[0213] The finished-coated tablets were weighed into an Al pan, and placed in a stability chamber at 25°C / 90% relative humidity for 48h. After 48h, the tablets were observed for tackiness. Additionally, the tablets exposed to 90% humidity were weighed and the difference in weight is calculated as % of moisture uptake of the coated tablets.TABLE 2: Coating Compositions (Ex.l- Ex.15)(Dry -basis addition level, % w / w)Ex. No. Reaction products of Example B mPEG4000 Other Coating Ingredients TotalDocket No.: 4478PCT. Red Yellow solids6rrt.% Talc TiO2iron iron content °' oxide oxide (%) Ex.l Bl 50 - 25 18 3.5 3.5 100 50 Ex.2 B2 30 - 30 30 5.0 5.0 100 40 Ex.3 B3 30 - 30 30 5.0 5.0 100 40 Ex.4 B4 50 - 25 18 3.5 3.5 100 50 Ex.5 B5 50 - 25 18 3.5 3.5 100 50 Ex.6 B6 50 - 25 18 3.5 3.5 100 50 Ex.7 B7 50 - 25 18 3.5 3.5 100 50 Ex.8 B8 20.9 29.1 25 18 3.5 3.5 100 50 Ex.9 B9 20.9 29.1 25 18 3.5 3.5 100 50Ex.10 B10 20.9 29.1 25 18 3.5 3.5 100 50 Ex.ll Bll 20.9 29.1 25 18 3.5 3.5 100 50 Ex.12 B12 50 29.1 25 18 3.5 3.5 100 50 Ex.13 B13 50 - 25 18 3.5 3.5 100 50 Ex.14 B14 50 - 25 18 3.5 3.5 100 50 Ex.15 B15 50 - 25 18 3.5 3.5 100 50 *Example 2 and 3 coatings were applied at 40% solidsTable 2A: Coating Compositions (Ex.16- Ex.24)(Dry -basis addition level, % w / w)Reactionproducts of Other Coating Ingredients solids Example B Polyde Mesoporous _.... conte. xtrose silica Red Yellow ° ntCwt.% Talc TiO₂ iron iron (%) oxide oxideEx.16 B16 50 10 1 14 21.5 0.5 3.5 100 50 Ex.17 B17 50 10 1 14 21.5 0.5 3.5 100 50 Ex.18 B18 50 10 1 14 21.5 0.5 3.5 100 50 Ex.19 B19 50 - - 21.43 21.43 3.57 3.57 100 40 Ex.20 B20 50 - - 21.43 21.43 3.57 3.57 100 40 Ex.21 B21 50 - - 21.43 21.43 3.57 3.57 100 50 Ex.22 B22 50 - - 21.43 21.43 3.57 3.57 100 40 Ex. 23 B23 50 - - 21.43 21.43 3.57 3.57 100 40Ex.24 B24 50 - - 21.43 21.43 3.57 3.57 100 50 *Example 2, 3, 19, 20, 22, and 23 coatings were applied at 40% solidsTABLE 3: Process Conditions to create Coated Tablets according to Examples 1- 24Process parameters Process settingsEquipment characteristicsDocket No.: 4478PCTPan type Vector LDCS fitted with a 2.5 L fully perforated panSpray gun type Schlick fitted with ABC nozzleNumber of spray guns 1Nozzle diameter, mm 1.0Specific process conditions usedPan loading, kg 2.0Pan speed, rpm 23 - 25Process air volume, m3 / h 60.0Inlet air temperature, °C 58.0 - 65.0Product temperature, °C 38.0 - 43.0Exhaust air temperature, °C 43.0 - 48.0Atomizing air pressure, bar 20.0 - 22.0Pattern air pressure, bar 22.0 - 24.0Spray rate, g / min 10.0 - 12.0TABLE 4: Coating Composition results of Examples 1-24 Examples No Polymer stability, 40°C / 75%RH for 2 weeks Coating performance CMC DE Color variability, CMC DE Ex.1 Stable Glossy tablets, excellent logo definition 0.09 Ex.2* Stable Glossy tablets, excellent logo definition 0.09 Ex.3* Polymer softened Glossy tablets, excellent logo definition 0.06 Ex.4 Polymer Softened High viscosity Ex.5 - High viscosity Ex.6 - - Ex.7 - Glossy tablets, excellent logo definition Ex.8 Polymer softened Oily layer separation on the coating solution surface, Glossy tablets, excellent logo definition 0.06Oily layer separation on the coating_ „ „., solution surface, Glossv tablets,Ex.9 PolyJmer softened „.. ’ 0.04excellent logo definitionOily layer separation on the coatingEx.10 Polymer softened Oily layer separation on the coating solution surface, Glossy tablets, excellent logo definitionOily layer separation on the coatingEx.11 Polymer softened Oily layer separation on the coating solution surface, Glossy tablets, excellent logo definition 0.08Oily layer separation on the coatingx, _ _ i x J solution surface. Glossy tablets. „Ex.12 PolyJmer softened excel nlent. l,ogo de xfi-n’i-.ti-on 0.06Ex.13 Stable Glossy tablets, excellent logo definition 0.05Ex.14 Stable Glossy tablets, excellent logo definition -Ex.15 Stable Glossy tablets, excellent logo definition 0.08Docket No.: 4478PCTEx.16 Stable Glossy tablets, excellent logo definition 0.22 Ex.17 Stable Tablets sticking to the panEx.18 Stable Glossy tablets, excellent logo definitionEx.19 Polymer agglomeration High viscosityEx.20 Polymer agglomeration High viscosityEx.21 Polymer agglomeration High viscosityEx.22 Polymer agglomeration High viscosityEx.23 Polymer agglomeration High viscosityEx.24 Polymer agglomeration High viscosity*Examples 2 and 3 coatings were applied at 40% solids

[0214] It is evident from Table 4 that the coating composition of Examples 1, 2, 3, 6, 7, 13, 14, 15, 16, 17, and 18 are stable after exposure to accelerated stability conditions (40°C / 75 % RH) for 2 weeks. These examples produced finished-coated tablets with good logo definition and nontackiness.

[0215] Example 25: Coating Composition using the reaction product of Example Bl at varied concentration

[0216] A coating composition was prepared in this example, containing the ingredients in weight proportions listed in Table 5. Three different coating compositions were prepared using 30.0 wt. %, 40.0 wt.%, and 50.0 wt.% of the reaction product of Example Bl. All the coating composition suspensions were prepared with total solid content of 50.0 % w / w. These coating composition suspensions were applied individually onto 2 Kg placebo tablets individually in a Vector LDCS fitted with a 2.5 L pan per the operating conditions shown in Table 3.TABLE 5: Coating Compositions having reaction product of Example Bl at different concentrations (30 - 50%)Dry-basis addition level, %w / wIngredients orange blue orange blue orange blue Reaction product of Example B1 50 50 40 40 30 30Example B 1Talc 25 25 26 26 30 25TiO₂ 18 17.9 26 26 30 25Red iron oxide 3.5 - 4 - 5Yellow iron oxide 3.5 - 4 - 5F“2■.4 ■.0 ■ 2.0 FD& C Blue 2 - 5.7 - 6.4 - 8.0Docket No.: 4478PCT(12 - 14%)Total 100 100 100 100 100 100TABLE 6: Coating Compositions results of Example 25gii fcif' Reaction+Reaction Product. Gloss,,Pigmentx. Coating quality roughness, Product ° concentration °Jgu ® ’° Sq jam good gloss, better logo30% definition, minor edge 110 5.48Iron chippingoxides 40% good gloss, better logo 116 5.85definition50% good gloss, better logo 116 5.46. _.. definitionExamExample B1good gloss, better logo30% definition, minor edge 96 6.00 FD& C chippingBlue 2 Lake 40% good gloss, better logo 108 5.48 definition50% good gloss, better logo 134 5.83definition

[0217] The reaction product of Example Bl was used at varying concentrations ranging from 30.0 - 50.0 wt.% on a dry basis in the coating composition to create tablets. All of these tablets were non-tacky and had good gloss (ideal gloss: >80 gu) and smooth surfaces, as represented in Table 6 and FIG. 1 of the accompanying drawings.

[0218] Example 26: Coating Compositions comprising a blend of the reaction product of Example Bl and other polymers (Ex.26-Ex.26H)

[0219] 8 -different coating compositions (in the form of suspensions) were prepared in this example using the ingredients in the weight proportions listed in Table 7. In these examples, the reaction product of example Bl was used along with other polymers, such as hydroxypropyl methylcellulose, polyvinyl alcohol, copovidone, and polydextrose. The coating compositions were prepared in the same manner as described, for example 25. These coating composition suspensions were applied individually onto 2 Kg placebo tablets individually in a Vector LDCS fitted with a 2.5 L pan per the operating conditions shown in Table 3.TABLE 7: Coating Compositions comprising a blend of the reaction product of Example Bl and other polymersDocket No.: 4478PCTIngredients Ex.26A Ex.26B Ex.26C Ex.26D Ex. 26E Ex. 26F Ex.26G Ex. 26H wt. %Reaction product of, 50.0 50.0 50.0 50.0 70.0 50.0 50.0 50.0 Example B 1HPMC 5cP 5.0.....Polyvinyl alcohol 5.0 - - - - - - - Copovidone - - 5.0 - Polydextrose - - - 5.0 15.0 - - 10 Calcium Carbonate - - - - - - - 15 Talc 18.86 18.86 18.86 18.86 15.0 25 25 Polysorbate 80 1.00 1.00 1.00 1.00TiO218.86 18.86 18.86 18.86 - 25 24.53 23.2 Red iron oxide 3.14 3.14 3.14 3.14 - - - 1.2 Yellow iron oxide 3.14 3.14 3.14 3.14.... FD& C Blue 2 (12 - 14%)...... 0.25 0.6 FD& C Yellow 6(18%) - - - - - - 0.22Total 100.00 100.00 100.00 100.0 100.0 100.0 100.0 100.0

[0220] Example 27: Hot-Melt Extrusion Coating (Ex.27A, Ex.27B, and Ex.27C)

[0221] Caffeine Citrate (API) and the reaction product of Example Bl were weighed in proportions listed in Table 8 and passed through the #20 mesh sieve to obtain a physical mixture thereof. The physical mixture was then blended for 15 minutes using a Turbula mixer. The obtained blend was passed through a Three-Tec ZE 9 mm twin-screw extruder (Three-Tec GmbH, Switzerland) equipped with a volumetric feeder using the process conditions mentioned in Table 9. Two mixing zones were used with 5 (90° offset angle) and 4 (60° offset angle) kneading elements. The resulting extrudates (granules) were collected, milled, and passed through a #20 mesh sieve to obtain hot-melt extruded milled granules (Caffeine Citrate-reaction product of Bl).TABLE 8: Coating Composition for melt granulationIngredients Coating Composition (%w / w) Ex.27A Ex.27B Ex. 27CCaffeine Citrate 20.0 30.0 40.0Reaction productof Bl(MSBO / 2mPEG4 80.0 70.0 60.0000 / 0.6Behenylalcohol)Docket No.: 4478PCTTotal 100.0 100.0 100.0TABLE 9: Twin-screw extrusion process parametersExtruder Three-Tec ZE 9 mmtwin-screw extruder(Three-Tec GmbH.Switzerland)Feeder Auto feederFeed rate 1.5 g / minBarrel temperature Zone 1: 50°CZone 2: 125°CZone 3: 125°CScrew speed 50 rpmTorque 2.5 - 11.0 Nm

[0222] Example 28 (Ex.28A, Ex.28B, and Ex.28C)

[0223] The hot-melt extruded milled granules of Example 27, a filler (Mannitol), and a disintegrant (Polyplasdone™ XL- 10) were weighed according to the amounts presented in Table 10 and blended for 7 minutes using a Turbula mixer. Finally, the lubricant (magnesium stearate) was added and mixed for another 2 minutes. The obtained blend was then compressed into tablets using a MEDELPHARM STYL’One tablet press.TABLE 10: Tablet Composition (Oral Solid Dosage Composition)Coating Compositions (%w / w)&Ex. 28A Ex. 28B Ex. 28C Hot-melt extruded milled granules: Ex.18A Ex.18B Ex.18C Caffeine Citrate 10 15 20 Reaction product of Ex. Bl 40 35 30 Mannitol 44.5 44.5 44.5 Polyplasdone™ XL-10 5.0 5.0 5.0 Magnesium stearate 0.5 0.5 0.5Total 100.0 100.0 100.0

[0224] Example 29: Tablet binder application (Ex.29A & Ex.29B)

[0225] Gabapentin (API) and the reaction product of example Bl (Ex. Bl) was weighed in proportions listed in Table 11 and passed through the #20 mesh sieve. This physical mixture was blended for 15 minutes using a Turbula mixer. The blend was passed through a Three-Tec ZE 9 mm twin-screw extruder (Three-Tec GmbH, Switzerland) equipped with a volumetric feeder using the process conditions mentioned in Table 12. Two mixing zones were used with 5 (90° offsetDocket No.: 4478PCTangle) and 4 (60° offset angle) kneading elements. The resulting extrudates (granules) were collected, milled using a Cuisinart mixer, passed through a #20 mesh sieve to obtain hot-melt extruded milled granules.TABLE 11: Binder composition for melt granulationIngredients Coating Compositions (%w / w) Ex.29A Ex.29B Gabapentin 95.0 90.0Reaction product of Ex. Bl(MSBO / 2mPEG4000 / 0.6Behenyl alcohol)Total 100.0 100.0TABLE 12: Twin-screw extrusion process parametersThree-Tec ZE 9 mm twin-screw extruderExtruder(Three-Tec GmbH, Switzerland)Feeder Auto feederFeed rate 1.5 g / minZone 1: 30°CBarrel temperature Zone 2: 125°CZone 3: 125°CScrew speed 50 rpmTorque 2.5 - 11.0 Nm

[0226] Example 30: (Ex.30A & Ex.30B)

[0227] The hot-melt extruded milled granules (Gabapentin-reaction product of Ex. Bl), a filler (microcrystalline cellulose 102), and a glidant (Cab-O-Sil M-5P) were weighed in amounts listed in Table 13 and blended for 7 minutes using a Turbula mixer. Finally, the lubricant (magnesium stearate) was added and mixed for another 2 minutes. The obtained blend was compressed into tablets using a MEDELPHARM STYL’One tablet press as per the operation conditions listed in Table 14. The obtained tablets were tested for tablet strength using a hardness tester.TABLE 13: Tablet (Oral Solid Dosage Composition)Coating Compositions (%w / w) IngredientsEx. 30A Ex. 30BDocket No.: 4478PCTHot-melt extruded milled granules Ex.20 A Ex.20BGabapentin 83.6 79.2TVO 4.4 8.8 Microcrystalline cellulose 102 10.0 10.0Cab-O-Sil M-5P 1.0 1.0Magnesium stearate 1.0 1.0Total 100.0 100.0TABLE 14: Parameters used for tabletingTablet press MEDPHARM STYL’OneTooling 0.75 / 0.343 OvalTablet weight Ex.30 A: 718 mgEx.30 B: 758 mgGabapentin dosage 600 mgTablet Strength 8-16 kP[00228J Comparative Examples 1 and 2

[0229] In this example, two different comparative coating compositions were prepared with 50% w / w total solid content by dissolving mPEG 2000 (Comparative Coating 1) or mPEG 4000 (Comparative Coating 2) along with other coating ingredients: talc, titanium dioxide, and colorants as listed in Table 15. These coating compositions were applied individually onto 2 Kg placebo tablets in a Vector LDCS fitted with a 2.5 L pan per the operating conditions shown in Table 16.TABLE 15: Comparative Coating Compositions 1 and 2Dry-basis addition level, %w / wIngredients Present Coating Comparative coating 1 Comparative coating 2 Composition of Ex 25 Reaction Product of Example B1mPEG 2000 50mPEG 4000 - 50Talc 25 25 25TiO218 18 18Docket No.: 4478PCTRed iron oxide 3.5 3.5 3.5 Yellow iron oxide 3.5 3.5 3.5 Total 100 100 100

[0230] As clearly indicated from FIG. 2A and FIG. 2B of the accompanying drawings, the comparative coating compositions 1 and 2 were phase separate, which is not favorable with any coating compositions. Contrary to this, tablets coated with the coating composition of Example 25 having reaction product of Example Bl produced tablets with good gloss, however, color discoloration was noticed after exposure to 40°C / 75% RH for 2 weeks (FIG.2C and D).

[0231] Comparative Examples 3 and 4

[0232] A comparative coating suspension (Comparative Coating 3) was made with 35 % w / w total solid content by using Copovidone and Hydroxypropyl cellulose (HPC). All other ingredients mentioned in Table 16 were also added under mixing and the mixing was continued for another 45 minutes. The coating suspension viscosity was measured using a Brookfield viscometer. This coating suspension was applied to 2 kg of the same lot of placebo tablets. The process conditions employed for tablet coatings are shown in Table 17. Similarly, another comparative coating suspension with PVA at 20% w / w total solid content was also prepared (Comparative coating 4). These comparative coating compositions were compared with the present coating composition of Example 25 with 50% w / w solid content.TABLE 16: Comparative Coating Compositions 3 and 4Dry -basis addition level, %w / wIngredients Comparative Coating 3 Comparative Coating 4 Present Coating Composition of Example 25orange blue orange blue orange blue Reaction product of 50 50 Example B 1Copovidone 32 26.50....HPC 10 0.22....PVA 40.0 40.0Talc 20 21.09 14.8 14.8 25 25 TiO218 17.9 18 17.9 18 17.9 PEG 3350 10.00 10.00 20.2 20.2Captex 300 3.00 3.00....Docket No.: 4478PCTRed iron oxide 3.5 - 3.5 3.5Yellow Iron Oxide 3.5 - 3.5 3.5FD& C Blue 2 (3 - 5%) 1.4 1.4 - 1.4 FD& C Blue 2 (12 - 14%) 5.7 5.7 - 5.7 Total 100 100 100 100 100 100TABLE 17: Process conditions for tablet coating by using Comparative Coatings 3, 4, and the present coating composition Ex.25Process settingsProcess parameters Comparative Coating 3 Comparative Coating 4 Present Coating Composition of Ex. 25 Equipment characteristicsVector LDCS fitted with Vector LDCS fitted Vector LDCS fitted Pan type a 2.5 L fully perforated with a 2.5 L fully with a 2.5 L fully - ’ pan perforated pan perforated pan „. Schlick fitted with ABC Schlick fitted with ABC Schlick fitted with Spray gun type Schlick fitted with ABC nozzle Schlick fitted with ABC nozzle Schlick fitted with ABC nozzle Number of spray guns 1 1 1 Nozzle diameter, mm 1.0 1.0 1.0 Specific process conditions usedPan loading, kg 2.0 2.0 2.0Pan speed, rpm 30 - 35 20 - 23 23 - 25 Process air volume, m³ / h 60 – 65 60.0 60.0 Inlet air temperature, °C 58.0 - 60.0 58.0 -60.0 58.0 - 65.0 Product temperature, °C 38.0 - 43.0 38.0 -43.0 38.0 - 43.0 Exhaust air temperature, °C 43.0 - 48.0 43.0 -48.0 43.0 - 48.0 Atomizing air pressure, bar 23.0 - 25.0 20.0 - 22.0 20.0 - 22.0 Pattern air pressure, bar 24.0 - 26.0 24.0 - 26.0 22.0 - 24.0 Spray rate, g / min 10.0 8.0 12.0TABLE 18: Comparative Coatings 3 & 4 vs. Present Coating Composition of Ex.25 PerformanceCoating ColorCoating „, solutionc„.,. variability, Gloss, u ace.. Color. Solids (% Coating quality roughness. Compositions viscosity;,x° CMC DE, guocP ’W / W)STDEVScRinlOrange 227 50 good gloss, crisp logo definition 0.07 116 5.5 Example 1 Blue 124 50 good gloss, crisp logo definition 0.08 134 5.8o acceptable gloss withn n,Comparative Orangegood logo definition 0.06 86 5.9 Coating 3 Blue 265 35 acceptable gloss with0.12 80 5.3 good logo definitionOrange 85 20 rough tablet surface 0.10 96 6.8Docket No.: 4478PCTComparativeBlue 105 20 rough tablet surface 0.05 76Coating 4

[0233] The present coating suspension viscosity of example 25 with was significantly less than the comparative coating suspensions 3 and 4, which is the greatest advantage of achieving 50% solids in the final coating formulation. FIG. 3 shows viscosity profile of comparative coating compositions vs. the present coating composition of Example 25. The present coating produced tablets were smoother with better gloss compared to the comparative coating formulations 3 and 4, as presented in Table 9. FIG. 4 shows the excellent gloss and logo definition with inventive coating at 50% of the total solids in the formulation. FIG. 5 demonstrates the significant coating time reduction with an inventive coating over comparative coatings.

[0234] Tablet coatingsTABLE 19: Coating Compositions comprising a blend of the reaction product of Example B18 and other polymersIngredients Ex.31 Ex.32 Ex.33 Ex.34 Ex.35Reaction product of Example B18 50.0 50.0 50.0 30.0 40.0Example B18 Methacrylic acid 5.0 - - - 5.0 HPMC 5cP - - 5.0Polyvinyl alcohol - 5.0 - 10.0HydroxypropylcelluloseCopovidone..... Polydextrose 9.0 9.0 9.0 13.0 19.0 Calcium Carbonate.....Talc 10.0 10.0 10.0 20.0 10.0 Polysorbate 80 - - - 1.0Mesoporous silica 1.0 1.0 1.0 1.0 1.0MCT.....TiO221.50 21.50 21.50 21.50 21.50Red iron oxide 0.5 0.5 0.5 0.5 0.5 Yellow iron oxide 3.0 3.0 3.0 3.0 3.0 Black iron oxide.....Total 100.00 100.00 100.00 100.0 100.0Docket No.: 4478PCTTABLE 19 continuedIngredients Ex.36 Ex.37 Ex.38 Ex.39 Ex.40Reaction product of Example B18 25.0 33.0 40.0 50.0 33.0Methacrylic acid - HPMC 5cP.....Polyvinyl alcohol 10.0 14.0 - - 14.0 Hydroxypropyl $celluloseCopovidone - - 10.0Polydextrose 12.0 10.0 16.0 9.0Calcium Carbonate - 38.352Talc 26.0 - 8.0 10.0 27.0 Polysorbate 80 1.0 1.0Mesoporous silica 1.0 1.0 - - 1.0MCT - 2.0 1.0 1.0TiO221.50 - 21.50 21.50 21.5Red iron oxide 0.5 0.005 0.5 0.5 0.5 Yellow iron oxide 3.0 0.64 3.0 3.0 3.0 Black iron oxide - 0.003 - Total 100.0 100.0 100.0 100.0 100.0

[0235] Embodiment AA An oral solid dosage (OSD) composition comprising a reaction product of: (i) a maleated natural oil comprising a natural oil with maleated functionality; and (ii) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof

[0236] Embodiment AB The oral solid dosage composition according to Embodiment AA, wherein the maleated natural oil is selected from the group consisting of maleated avocado oils, maleated coconut oils, maleated corn oils, maleated cottonseed oils, maleated jojoba oils, maleated linseed oils, maleated nut oils, maleated olive oils, maleated palm oils, maleated raisin oils, maleated rapeseed oils, maleated safflower oils, maleated sesame oils, maleated soybean oils, maleated squash oils, maleated sunflower oils, maleated almond oils, maleated canola oils, maleated flaxseed oils, maleated grapeseed oils, maleated palm kernel oils, maleated peanut oils, maleated walnut oils, maleated chickpea oils, maleated clary sage oils and mixtures thereof;Docket No.: 4478PCTwherein the functionalized or unfunctionalized moiety is a hydrophobic moiety selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof; wherein the functionalized or unfunctionalized moiety is a hydrophilic moiety selected from the group consisting of hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether amine monoalkyl ethers, hydrophilic polyether alcohol monoaryl ethers, hydrophilic polyether amine monoaryl ethers, hydrophilic polyether alcohol monoalkaryl ethers, hydrophilic polyether amine monoalkaryl ethers and combinations thereof; wherein the hydrophilic polyether alcohol monoalkyl ether has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons; and wherein the hydrophilic polyether alcohol monoalkyl ether has a weight average molecular weight ranging from about 2,000 Daltons to about 4,000 Daltons.

[0237] Embodiment AC The oral solid dosage composition according to Embodiment AB, wherein the hydrophilic polyether amine monoalkyl ether and hydrophilic polyether amine monoaralkyl ether comprises one or more structures selected from the following group of structures:Me or Et, wherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

[0238] Embodiment AD The oral solid dosage composition according to embodiment AA, wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof; wherein the additional hydrophilic moiety is selected from the group consisting of hydrophilic polyether glycols, hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether polyamines, hydrophilic polyether amine monoalkyl ethers, hydrophilic polyether alcohol monoaryl ethers, hydrophilic polyether amine monoaryl ethers, hydrophilic polyether alcohol monoalkaryl ethers, hydrophilic polyether amine monoalkaryl ethers andDocket No.: 4478PCTcombinations thereof; wherein the hydrophilic polyether alcohol monoalkyl ether or hydrophilic poly ether glycol has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons; wherein the hydrophilic polyether alcohol monoalkyl ether or hydrophilic poly ether glycol has a weight average molecular weight ranging from about 2,000 Daltons to about 4,000 Daltons; wherein the additional hydrophilic polyether amine monoalkyl ether and hydrophilic polyether amine monoaralkyl ether comprises one or more structures selected from the following group of structures:Me or EtC₉H₁₉, wherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14,wherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14; wherein the additional hydrophobic moiety is selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof; wherein the hydrophobic alcohol or hydrophobic amine is a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl alcohol or amine; wherein the hydrophobic amine is selected from the group consisting of benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecylamine, undecylamine, pentadecylamine, 2-methylbutylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

[0239] Embodiment AE The oral solid dosage composition according to Embodiment AA, wherein the composition comprises a reaction product of: a maleated soybean oil; and behenyl alcohol or polyethylene glycol monomethyl ether, or combinations thereof.

[0240] Embodiment AF The oral solid dosage composition according to Embodiment AE, wherein the reaction product further comprises at least one additional moiety selected from theDocket No.: 4478PCTgroup consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0241] Embodiment AG The oral solid dosage composition according to embodiment AA, wherein the composition comprises a reaction product of: a maleated soybean oil; behenyl alcohol; and polyethylene glycol monomethyl ether.

[0242] Embodiment AH The oral solid dosage composition according to embodiment AG, wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0243] Embodiment Al The oral solid dosage composition according to embodiment AA, wherein the reaction product comprises one or more structures selected from the following group of structures:, wherein n is integer from about 20 to about 200, or from about 40 to about 100, and Me is methyl.Docket No.: 4478PCT

[0244] Embodiment AJ The oral solid dosage composition according to embodiment AA, wherein the oral solid dosage composition further comprises at least one ingredient selected from the group consisting of an active pharmaceutical ingredient, a filler, a binder, a surfactant, a disintegrating agent, a lubricant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof; wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides; wherein the reaction product is present in an amount from about 5.0 wt. % to about 70.0 wt. % of the total oral solid dosage composition; wherein the ingredient is present in an amount from about 0.1 wt. % to about 95.0 wt. % of the total oral solid dosage composition; wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies; wherein the oral solid dosage composition is a coated oral solid dosage composition; wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition; wherein the coated pharmaceutical composition is a dry film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition.

[0245] Embodiment AK A granule composition comprising: (i) the reaction product of claim AA; and (ii) at least one active pharmaceutical ingredient.

[0246] Embodiment AL The granule composition according to embodiment AK, wherein the reaction product is functioning as a binding agent; wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides; wherein the reaction product is present in an amount from about 5.0 wt. % to about 20.0 wt. % of the total granule composition weight; wherein the active pharmaceutical ingredient is present in an amount from about 80.0 wt. % to about 95.0 wt. % of the total granule composition weight.

[0247] Embodiment AM An oral solid dosage composition comprising: (i) the granule composition of embodiment AK; and (ii) at least one additional ingredient.

[0248] Embodiment AN The oral solid dosage form according to embodiment AM, wherein the additional ingredient is selected from the group consisting of a filler, an additional binder, aDocket No.: 4478PCTsurfactant, a disintegrating agent, a lubricant, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0249] Embodiment AO The oral solid dosage composition according to embodiment AM, wherein the granule composition is present in an amount from about 50.0 wt. % to about 90.0 wt. % of the total oral solid dosage composition; wherein the additional ingredient is present in an amount from about 10.0 wt. % to about 50.0 wt. % of the total oral solid dosage composition; wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies; wherein the oral solid dosage composition is a coated oral solid dosage composition; wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition; and wherein the coated pharmaceutical composition is a dry-film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition.

[0250] Embodiment AP A coating composition for an oral solid dosage form comprising: (i) the reaction product of claim AA; and (ii) at least one ingredient.

[0251] Embodiment AQ The coating composition according to embodiment AP, wherein the ingredient is selected from the group consisting of a surfactant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0252] Embodiment AR The coating composition according to embodiment AP, wherein the reaction product is present in an amount from about 5.0 wt. % to about 70.0 wt. % of the total coating composition weight; wherein the ingredient is present in an amount from about 30.0 wt. % to about 95.0 wt. % of the total coating composition weight; wherein the coating composition is present in the form of a dry powder; wherein the coating composition is present in the form of a solid phase of a solvent dispersion with a solid content from about 15.0 % to about 60.0 % by weight, wherein the solvent is an aqueous solvent, an organic solvent, or a combination thereof; wherein the coating composition is used for coating oral solid dosage forms selected from the group consisting of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.

[0253] Embodiment AS A coating composition for a pharmaceutical tablet comprising: (i) the reaction product of embodiment AA; and (ii) at least one ingredient selected from theDocket No.: 4478PCTgroup consisting of a surfactant, a film forming agent, a plasticizer, a colorant, an anti-tacking agent or a glidant, a plasticizer, a sweetener, and combinations thereof.

[0254] Embodiment BA An oral solid dosage (OSD) composition comprising a reaction product of: (i) a maleated natural oil comprising a natural oil with maleated functionality; and (ii) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof.

[0255] Embodiment BB The oral solid dosage composition according to Embodiment BA, wherein the maleated natural oil is selected from the group consisting of maleated avocado oils, maleated coconut oils, maleated corn oils, maleated cottonseed oils, maleated jojoba oils, maleated linseed oils, maleated nut oils, maleated olive oils, maleated palm oils, maleated raisin oils, maleated rapeseed oils, maleated safflower oils, maleated sesame oils, maleated soybean oils, maleated squash oils, maleated sunflower oils, maleated almond oils, maleated canola oils, maleated flaxseed oils, maleated grapeseed oils, maleated palm kernel oils, maleated peanut oils, maleated walnut oils, maleated chickpea oils, maleated clary sage oils and mixtures thereof; wherein the functionalized or unfunctionalized moiety is a hydrophobic moiety selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof; wherein the functionalized or unfunctionalized moiety is a hydrophilic moiety selected from the group consisting of hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether amine monoalkyl ethers, hydrophilic polyether alcohol monoaryl ethers, hydrophilic polyether amine monoaryl ethers, hydrophilic polyether alcohol monoalkaryl ethers, hydrophilic polyether amine monoalkaryl ethers and combinations thereof; wherein the hydrophilic polyether alcohol monoalkyl ether has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons; and wherein the hydrophilic poly ether alcohol monoalkyl ether has a weight average molecular weight ranging from about 2,000 Daltons to about 4,000 Daltons

[0256] Embodiment BC The oral solid dosage composition according to Embodiment BB, wherein the hydrophilic polyether amine monoalkyl ether and hydrophilic polyether amine monoaralkyl ether comprises one or more structures selected from the following group of structures:Docket No.: 4478PCTMe or Etwherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

[0257] Embodiment BD The oral solid dosage composition according to embodiment BA, wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, hydrophilic polyether amine monoalkaryl ether and combinations thereof; wherein the additional hydrophilic moiety is selected from the group consisting of hydrophilic polyether glycols, hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether polyamines, hydrophilic polyether amine monoalkyl ethers, hydrophilic polyether alcohol monoaryl ethers, hydrophilic polyether amine monoaryl ethers, hydrophilic polyether alcohol monoalkaryl ethers, hydrophilic polyether amine monoalkaryl ethers and combinations thereof; wherein the hydrophilic polyether alcohol monoalkyl ether or hydrophilic polyether glycol has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons; wherein the hydrophilic polyether alcohol monoalkyl ether or hydrophilic polyether glycol has a weight average molecular weight ranging from about 2,000 Daltons to about 4,000 Daltons; wherein the additional hydrophilic polyether amine monoalkyl ether and hydrophilic polyether amine monoaralkyl ether comprises one or more structures selected from the following group of structures:Me or Etwherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14, wherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl,Docket No.: 4478PCTand f is an integer from about 13 to about 14; wherein the additional hydrophobic moiety is selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof; wherein the hydrophobic alcohol or hydrophobic amine is a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl alcohol or amine; wherein the hydrophobic amine is selected from the group consisting of benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecylamine, undecylamine, pentadecylamine, 2-methylbutylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

[0258] Embodiment BE The oral solid dosage composition according to Embodiment BA, wherein the composition comprises a reaction product of: a maleated soybean oil; and behenyl alcohol or polyethylene glycol monomethyl ether, or combinations thereof; wherein the composition further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0259] Embodiment BF The oral solid dosage composition according to embodiment BA, wherein the composition comprises a reaction product of: a maleated soybean oil; behenyl alcohol; and polyethylene glycol monomethyl ether; wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0260] Embodiment BG The oral solid dosage composition according to embodiment BA, wherein the reaction product comprises one or more structures selected from the following group of structures:Docket No.: 4478PCT, wherein n is integer from about 20 to about 200, or from about 40 to about 100, and Me is methyl.

[0261] Embodiment BH The oral solid dosage composition according to embodiment BA, wherein the oral solid dosage composition further comprises at least one ingredient selected from the group consisting of an active pharmaceutical ingredient, a filler, a binder, a surfactant, a disintegrating agent, a lubricant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof; wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides; wherein the reaction product is present in an amount from about 5.0 wt. % to about 70.0 wt. % of the total oral solid dosage composition; wherein the ingredient is present in an amount from about 0.1 wt. % to about 95.0 wt. % of the total oral solid dosage composition; wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies; wherein the oral solid dosage composition is a coated oral solid dosage composition; wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition; wherein the coated pharmaceutical composition is a dry film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition

[0262] Embodiment BI A granule composition comprising: (i) the reaction product of claim BA; and (ii) at least one active pharmaceutical ingredient; wherein the reaction product is functioning as a binding agent; wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides; wherein the reaction product is present in an amount from about 5.0 wt. % to about 20.0 wt. % of the total granule composition weight; wherein the active pharmaceuticalDocket No.: 4478PCTingredient is present in an amount from about 80.0 wt. % to about 95.0 wt. % of the total granule composition weight.

[0263] Embodiment BJ An oral solid dosage composition comprising: (i) the granule composition of embodiment BB; and (ii) at least one additional ingredient.

[0264] Embodiment BK The oral solid dosage form according to embodiment BJ, wherein the ingredient is selected from the group consisting of a filler, an additional binder, a surfactant, a disintegrating agent, a lubricant, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0265] Embodiment BL The oral solid dosage composition according to embodiment BJ, wherein the granule composition is present in an amount from about 50.0 wt. % to about 90.0 wt. % of the total oral solid dosage composition; wherein the ingredient is present in an amount from about 10.0 wt. % to about 50.0 wt. % of the total oral solid dosage composition; wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies; wherein the oral solid dosage composition is a coated oral solid dosage composition; wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition; and wherein the coated pharmaceutical composition is a dry-film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition.

[0266] Embodiment BM A coating composition for an oral solid dosage form comprising: (i) the reaction product of embodiment BA; and (ii) at least one ingredient; wherein the ingredient is selected from the group consisting of a surfactant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof; wherein the reaction product is present in an amount from about 5.0 wt. % to about 70.0 wt. % of the total coating composition weight; wherein the ingredient is present in an amount from about 30.0 wt. % to about 95.0 wt. % of the total coating composition weight; wherein the coating composition is present in the form of a dry powder; wherein the coating composition is present in the form of a solid phase of a solvent dispersion with a solid content from about 15.0 % to about 60.0 % by weight, wherein the solvent is an aqueous solvent, an organic solvent, or a combination thereof; wherein the coating composition is used for coating oral solid dosage forms selected from theDocket No.: 4478PCTgroup consisting of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.

[0267] Embodiment BN A coating composition for a pharmaceutical tablet comprising: (i) the reaction product of embodiment BA; and (ii) at least one ingredient selected from the group consisting of a surfactant, a film forming agent, a plasticizer, a colorant, an anti-tacking agent or a glidant, a plasticizer, a sweetener, and combinations thereof.

[0268] Embodiment CA An oral solid dosage (OSD) composition comprising a reaction product of: (i) a maleated natural oil comprising a natural oil with maleated functionality; and (ii) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof.

[0269] Embodiment CB The oral solid dosage composition according to embodiment CA, wherein the maleated natural oil is selected from the group consisting of maleated avocado oils, maleated coconut oils, maleated corn oils, maleated cottonseed oils, maleated jojoba oils, maleated linseed oils, maleated nut oils, maleated olive oils, maleated palm oils, maleated raisin oils, maleated rapeseed oils, maleated safflower oils, maleated sesame oils, maleated soybean oils, maleated squash oils, maleated sunflower oils, maleated almond oils, maleated canola oils, maleated flaxseed oils, maleated grapeseed oils, maleated palm kernel oils, maleated peanut oils, maleated walnut oils, maleated chickpea oils, maleated clary sage oils and mixtures thereof.

[0270] Embodiment CC The oral solid dosage composition according to embodiment CA, wherein the maleated natural oil is a maleated soybean oil.

[0271] Embodiment CD The oral solid dosage composition according to embodiment CA, wherein the functionalized or unfunctionalized moiety is a hydrophobic moiety selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof.

[0272] Embodiment CE The oral solid dosage composition according to embodiment CA, wherein the hydrophobic alcohol or hydrophobic amine is a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl alcohol or amine.

[0273] Embodiment CF The oral solid dosage composition according to embodiment CA, wherein the hydrophobic alcohol is selected from the group consisting of hexanol, heptanol,Docket No.: 4478PCTnonanol, decanol, dodecanol, phenol, ethylbenzyl alcohol, 2-ethyl-l -hexanol, 1 -octanol, 2-octanol, 2 -butyl- 1 -octanol, 2-octyl-l -dodecyl alcohol, 1 -tetradecanol, 2-tetradecanol, 1 -hexadecanol, 2-hexadecanol, 1-octadecanol 3,7-dimethyl-l-octanol, 2-propyl-l -pentanol, 4-methyl-l -pentanol, cetyl alcohol, stearyl alcohol, eicosanol, behenyl alcohol, and combinations thereof.Embodiment CG The oral solid dosage composition according to embodiment CD, wherein the hydrophobic alcohol is behenyl alcohol.

[0274] Embodiment CH The oral solid dosage composition according to embodiment CA, wherein the hydrophobic amine is selected from the group consisting of benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecylamine, undecylamine, pentadecylamine, 2-methyl-butylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

[0275] Embodiment CI The oral solid dosage composition according to embodiment CA, wherein the silicon-based compound is selected from the group consisting of aminopropylmethylsiloxane-dimethylsiloxane, N-ethylaminoisobutyl terminated poly dimethylsiloxane, poly(1,1-dimethylsilazane) telomer, aminopropyl terminated polydimethylsiloxane, monoaminopropyl terminated polydimethyl siloxane, (tetramethyl piperidinyloxy) propylmethyl siloxane)-dimethylsiloxane copolymer, polydimethylsiloxane, carbinol (hydroxyl) terminated polydimethyl siloxane, monocarbinol terminated polydimethylsiloxane, monocarbinol terminated functional polydimethylsiloxane, [Bis(hydroxyethyl) amine] terminated polydimethylsiloxane, silanol terminated polydimethyl siloxane, silanol terminated polydiphenyl siloxane, dodecylmethyl siloxane- hydroxypolyalkylene oxypropyl methylsiloxane, and combinations thereof.

[0276] Embodiment CJ The oral solid dosage composition according to embodiment CA, wherein the functionalized or unfunctionalized moiety is a hydrophilic moiety selected from the group consisting of hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether amine monoalkyl ethers, hydrophilic polyether alcohol monoaryl ethers, hydrophilic polyether amine monoaryl ethers, hydrophilic polyether alcohol monoalkaryl ethers, hydrophilic polyether amine monoalkaryl ethers and combinations thereof.Docket No.: 4478PCT

[0277] Embodiment CK The oral solid dosage composition according to embodiment CJ, wherein the hydrophilic polyether alcohol monoalkyl ether is selected from the group consisting of polyethylene glycol monomethyl ethers, polyethylene glycol monoethyl ethers, polypropylene glycol monomethyl ethers, polypropylene glycol monoethyl ethers, poly(ethylene glycol-co-propylene glycol) monomethyl ethers, poly(ethylene glycol-co-propylene glycol) monoethyl ethers, and combinations thereof.[00278J Embodiment CL The oral solid dosage composition according to embodiment CJ, wherein the hydrophilic polyether alcohol monoalkyl ether is polyethylene glycol monomethyl ether.

[0279] Embodiment CM The oral solid dosage composition according to embodiment CJ, wherein the hydrophilic polyether alcohol monoalkyl ether has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons.

[0280] Embodiment CN The oral solid dosage composition according to embodiment CJ, wherein the hydrophilic polyether alcohol monoalkyl ether has a weight average molecular weight ranging from about 2,000 Daltons to about 4,000 Daltons.

[0281] Embodiment CO The oral solid dosage composition according to embodiment CJ, wherein the hydrophilic polyether amine monoalkyl ether and hydrophilic polyether amine monoaralkyl ether comprises one or more structures selected from the following group of structures:Me or Etwherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

[0282] Embodiment CP The oral solid dosage composition according to embodiment CG, wherein the reaction product further comprises at least one additional moiety selected from theDocket No.: 4478PCTgroup consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0283] Embodiment CQ The oral solid dosage composition according to embodiment CP wherein the additional hydrophilic moiety is selected from the group consisting of hydrophilic polyether glycols, hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether polyamines, hydrophilic polyether amine monoalkyl ethers, and combinations thereof.

[0284] Embodiment CR The oral solid dosage composition according to embodiment CQ, wherein - the hydrophilic polyether alcohol monoalkyl ether is selected from the group consisting of polyethylene glycol monomethyl ethers, polyethylene glycol monoethyl ethers, polypropylene glycol monomethyl ethers, polypropylene glycol monoethyl ethers, polyethylene glycol-co-propylene glycol) monomethyl ethers, poly(ethylene glycol-co-propylene glycol) monoethyl ethers, and combinations thereof; and - the hydrophilic polyether glycol is selected from the group consisting of polyethylene glycol, polypropylene glycol, polyethylene glycol-co-propylene glycol), and combinations thereof.

[0285] Embodiment CS The oral solid dosage composition according to embodiment CR wherein - the hydrophilic polyether alcohol monoalkyl ether is polyethylene glycol monomethyl ether; and - the hydrophilic polyether glycol is polyethylene glycol.

[0286] Embodiment CT The oral solid dosage composition according to embodiment CQ wherein the hydrophilic polyether alcohol monoalkyl ether or hydrophilic polyether glycol has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons.

[0287] Embodiment CU The oral solid dosage composition according to embodiment CQ, wherein the hydrophilic polyether alcohol monoalkyl ether or hydrophilic polyether glycol has a weight average molecular weight ranging from about 2,000 Dalton to about 4,000 Daltons.

[0288] Embodiment CV The oral solid dosage composition according to embodiment CQ, wherein the additional hydrophilic polyether amine monoalkyl ether and hydrophilic polyether amine monoaralkyl ether comprises one or more structures selected from the following group of structures:Docket No.: 4478PCTMe or Etwherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

[0289] Embodiment CW The oral solid dosage composition according to embodiment CP, wherein the additional hydrophobic moiety is selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof.

[0290] Embodiment CX The oral solid dosage composition according to embodiment CW, wherein the hydrophobic alcohol or hydrophobic amine is a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl alcohol or amine.

[0291] Embodiment CY The oral solid dosage composition according to embodiment CW, wherein the hydrophobic alcohol is selected from the group consisting of hexanol, heptanol, nonanol, decanol, dodecanol, phenol, ethylbenzyl alcohol, 2-ethyl-l -hexanol, 1 -octanol, 2-octanol, 2 -butyl- 1 -octanol, 2-octyl-l -dodecyl alcohol, 1 -tetradecanol, 2-tetradecanol, 1 -hexadecanol, 2-hexadecanol, 1-octadecanol 3,7-dimethyl-l-octanol, 2-propyl-l -pentanol, 4-methyl-l-pentanol, cetyl alcohol, stearyl alcohol, eicosanol, behenyl alcohol, and combinations thereof.

[0292] Embodiment CZ The oral solid dosage composition according to embodiment CW, wherein the hydrophobic alcohol is behenyl alcohol.

[0293] Embodiment DA The oral solid dosage composition according to embodiment CW, wherein the hydrophobic amine is selected from the group consisting of benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecylamine, undecylamine, pentadecylamine, 2-methylbutylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

[0294] Embodiment DB The oral solid dosage composition according to embodiment CW, wherein the silicon-based compound is selected from the group consisting of aminopropylmethylDocket No.: 4478PCTsiloxane-dimethyl siloxane, N-ethylaminoisobutyl terminated polydimethylsiloxane, poly(1,1-dimethylsilazane) telomer, aminopropyl terminated polydimethylsiloxane, monoaminopropyl terminated polydimethylsiloxane, (tetramethylpiperidinyloxy)propylmethylsiloxane]-dimethylsiloxane copolymer, polydimethylsiloxane, carbinol (hydroxyl) terminated polydimethylsiloxane, monocarbinol terminated polydimethylsiloxane, monocarbinol terminated functional polydimethylsiloxane, [Bis(hydroxyethyl)amine] terminated polydimethylsiloxane, silanol terminated polydimethyl siloxane, silanol terminated polydiphenylsiloxane, dodecylmethylsiloxane-hydroxypolyalkyleneoxypropyl methyl siloxane, and combinations thereof.

[0295] Embodiment DC The oral solid dosage composition according to embodiment CA, wherein the composition comprises a reaction product of: (i) a maleated soybean oil; and (ii) behenyl alcohol or polyethylene glycol monomethyl ether, or combinations thereof.

[0296] Embodiment DD The oral solid dosage composition according to embodiment CA, wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0297] Embodiment DE The oral solid dosage composition according to embodiment CA, wherein the composition comprises a reaction product of:(i) a maleated soybean oil;(ii) behenyl alcohol; and(iii) polyethylene glycol monomethyl ether.

[0298] Embodiment DF The oral solid dosage composition according to embodiment DE, wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

[0299] Embodiment DG The oral solid dosage composition according to embodiment DE, wherein the reaction product comprises one or more structures selected from the following group of structures:Docket No.: 4478PCTwherein n is integer from about 20 to about 200, or from about 40 to about 100, and Me is methyl.

[0300] Embodiment DH The oral solid dosage composition according to embodiment CA, wherein the oral solid dosage composition further comprises at least one ingredient selected from the group consisting of an active pharmaceutical ingredient, a filler, a binder, a surfactant, a disintegrating agent, a lubricant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0301] Embodiment DI The oral solid dosage composition according to embodiment CA, wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides.

[0302] Embodiment DJ The oral solid dosage composition according to embodiment CA, wherein the filler is selected from the group consisting of monosaccharides, disaccharides, polysaccharides, inorganic acid salts, and combinations thereof.Docket No.: 4478PCT

[0303] Embodiment DK The oral solid dosage composition according to embodiment DJ, wherein the filler is selected from the group consisting of cellulose, lactose, sucrose, sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, calcium sulfate, Bentonite, Kaolin, calcium diphosphate dihydrate and hydrosulfates, microcrystalline cellulose, and combinations thereof.

[0304] Embodiment DL The oral solid dosage composition according to embodiment DH, wherein the binder is selected from the group consisting of polyvinyl pyrrolidone, starch, pregelatinized starch, gum arabic, tragacanth gum, guar gum, pectin, wax-based binders, polyethylene oxide, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and combinations thereof.

[0305] Embodiment DM The oral solid dosage composition according to embodiment DH, wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

[0306] Embodiment DN The oral solid dosage composition according to embodiment DH, wherein the disintegrating agent is selected from the group consisting of crospovidone, crosscarmellose sodium, low substituted hydroxypropyl cellulose, sodium starch glycolate, and combinations thereof.

[0307] Embodiment DO The oral solid dosage composition according to embodiment DH, wherein the lubricant is selected from the group consisting of calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, palmitic acid, calcium silicate, mineral oils, bees wax, carnauba wax, hydrogenated vegetable oils, glyceryl behenate, sodium stearyl fumarate, and combinations thereof.

[0308] Embodiment DP The oral solid dosage composition according to embodiment DH, wherein the film forming agent is selected from the group consisting of cellulose ethers, synthetic polymers, sugars, and combinations thereof.

[0309] Embodiment DQ The oral solid dosage composition according to embodiment DP, wherein the cellulose ether is selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), carboxymethyl celluloseDocket No.: 4478PCT(CMC), and combinations thereof; the synthetic polymer is selected from the group consisting of polyvinylpyrrolidone (PVP), copovidone, polyvinyl alcohol, polyethylene oxide, ethylene glycol and vinyl alcohol graft copolymer, and combinations thereof; and the sugar is selected from the group consisting of polydextrose, maltodextrin, sucrose, dextrose, lactose, and combinations thereof.

[0310] Embodiment DR The oral solid dosage composition according to embodiment DH, wherein the colorant includes at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red, yellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.

[0311] Embodiment DS The oral solid dosage composition according to embodiment DH, wherein the anti-tacking agent or the glidant is selected from the group consisting of talc, silica, medium chain triglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof.

[0312] Embodiment DT The oral solid dosage composition according to embodiment DH, wherein the plasticizer is selected from the group consisting of propylene glycol, glycerol, polyethylene glycols (200-6000), citrate esters, glyceryl triacetate, dibutyl sebacate, phthalate esters, acetylated monoglycerides, castor oil, mineral oil, and combinations thereof

[0313] Embodiment DU The oral solid dosage composition according to embodiment CA, wherein the reaction product is present in an amount from about 5.0 wt.% to about 70.0 wt.% of the total oral solid dosage composition.

[0314] Embodiment DV The oral solid dosage composition according to embodiment CA, wherein the ingredient is present in an amount from about 0.1 wt. % to about 95.0 wt. % of the total oral solid dosage composition.

[0315] Embodiment DW The oral solid dosage composition according to embodiment CA, wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.Docket No.: 4478PCT

[0316] Embodiment DX The oral solid dosage composition according to embodiment DW, wherein the oral solid dosage composition is a coated oral solid dosage composition.

[0317] Embodiment DY The oral solid dosage composition according to embodiment CA, wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition.

[0318] Embodiment DG The oral solid dosage composition according to embodiment CA, wherein the coated pharmaceutical composition is a dry film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition.

[0319] Embodiment DZ A granule composition comprising:(i) the reaction product of embodiment DH; and (ii) at least one active pharmaceutical ingredient.

[0320] Embodiment EA The granule composition according to embodiment DZ, wherein the reaction product is functioning as a binding agent.

[0321] Embodiment EB The granule composition according to embodiment DZ, wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides.

[0322] Embodiment EC The granule composition according to embodiment DZ, wherein the reaction product is present in an amount from about 5.0 wt. % to about 20.0 wt. % of the total granule composition weight.

[0323] Embodiment ED The granule composition according to embodiment DZ, wherein the active pharmaceutical ingredient is present in an amount from about 80.0 wt. % to about 95.0 wt. % of the total granule composition weight.

[0324] Embodiment EE An oral solid dosage composition comprising:(i) the granule composition of embodiment DZ; and(ii) at least one additional ingredient.

[0325] Embodiment EF The oral solid dosage form according to embodiment EE, wherein the ingredient is selected from the group consisting of a filler, an additional binder, a surfactant, aDocket No.: 4478PCTdisintegrating agent, a lubricant, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0326] Embodiment EG The oral solid dosage composition according to embodiment EF, wherein the filler is selected from the group consisting of monosaccharides, disaccharides, polysaccharides, inorganic acid salts, and combinations thereof.

[0327] Embodiment EH The oral solid dosage composition according to embodiment EG, wherein the filler is selected from the group consisting of cellulose, lactose, sucrose, sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, calcium sulfate,, Bentonite, Kaolin, calcium diphosphate dihydrate and hydrosulfates, microcrystalline cellulose, and combinations thereof.

[0328] Embodiment El The oral solid dosage composition according to embodiment EF, wherein the additional binder is selected from the group consisting of polyvinyl pyrrolidone, starch, pre-gelatinized starch, gum arabic, tragacanth gum, guar gum, pectin, wax-based binders, polyethylene oxide, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and combinations thereof.

[0329] Embodiment EJ The oral solid dosage composition according to embodiment EF, wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

[0330] Embodiment EK The oral solid dosage composition according to embodiment EF, wherein the disintegrating agent is selected from the group consisting of crospovidone, crosscarmellose sodium, low substituted hydroxypropyl cellulose, sodium starch glycolate, and combinations thereof.

[0331] Embodiment EL The oral solid dosage composition according to embodiment CF, wherein the lubricant is selected from the group consisting of calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, palmitic acid, calcium silicate, mineral oils, bees wax, carnauba wax, hydrogenated vegetable oils, glyceryl behenate, sodium stearyl fumarate, and combinations thereof.Docket No.: 4478PCT

[0332] Embodiment EM The oral solid dosage composition according to embodiment CF, wherein the colorant includes at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red, yellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.

[0333] Embodiment EN The oral solid dosage composition according to embodiment EF, wherein the anti-tacking agent or the glidant is selected from the group consisting of talc, silica, medium chain triglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof.

[0334] Embodiment EO The oral solid dosage composition according to embodiment EE, wherein the granule composition is present in an amount from about 50.0 wt.% to about 90.0 wt.% of the total oral solid dosage composition.

[0335] Embodiment EP The oral solid dosage composition according to embodiment EE, wherein the ingredient is present in an amount from about 10.0 wt.% to about 50.0 wt.% of the total oral solid dosage composition.

[0336] Embodiment EQ The oral solid dosage composition according to embodiment EE, wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.

[0337] Embodiment ER The oral solid dosage composition according to embodiment EQ, wherein the oral solid dosage composition is a coated oral solid dosage composition.

[0338] Embodiment ES The oral solid dosage composition according to embodiment ER, wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition.

[0339] Embodiment ET The oral solid dosage composition according to embodiment ES, wherein the coated pharmaceutical composition is a dry-film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition.Docket No.: 4478PCT

[0340] Embodiment EU A coating composition for an oral solid dosage form comprising:(i) the reaction product of embodiment AA; and(ii) at least one ingredient.

[0341] Embodiment EV The coating composition according to embodiment EU, wherein the ingredient is selected from the group consisting of a surfactant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

[0342] Embodiment EW The coating composition according to embodiment EV, wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

[0343] Embodiment EX The coating composition according to embodiment EV, wherein the film forming agent is selected from the group consisting of cellulose ethers, synthetic polymers, sugars, and combinations thereof.

[0344] Embodiment EY The coating composition according to embodiment EF, wherein the cellulose ether is selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), carboxymethyl cellulose (CMC), and combinations thereof; the synthetic polymer is selected from the group consisting of polyvinylpyrrolidone (PVP), copovidone, polyvinyl alcohol, ethylene glycol and vinyl alcohol graft copolymer, and combinations thereof; and the sugar is selected from the group consisting of polydextrose, maltodextrin, sucrose, dextrose, lactose, and combinations thereof.

[0345] Embodiment EZ The coating composition according to embodiment EV, wherein the colorant includes at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red, yellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.

[0346] Embodiment FA The coating composition according to embodiment EV, wherein the anti-tacking agent or the glidant is selected from the group consisting of talc, silica, medium chainDocket No.: 4478PCTtriglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof

[0347] Embodiment FB The oral solid dosage composition according to embodiment EV, wherein the plasticizer is selected from the group consisting of propylene glycol, glycerol, polyethylene glycols (200-6000), citrate esters, glyceryl triacetate, dibutyl sebacate, phthalate esters, acetylated monoglycerides, castor oil, mineral oil, and combinations thereof.

[0348] Embodiment FC The coating composition according to embodiment EU, wherein the reaction product is present in an amount from about 5.0 wt. % to about 70.0 wt. % of the total coating composition weight.

[0349] Embodiment FD The coating composition according to embodiment EU, wherein the ingredient is present in an amount from about 30.0 wt.% to about 95.0 wt.% of the total coating composition weight.

[0350] Embodiment FE The coating composition according to embodiment EU, wherein the coating composition is present in the form of a dry powder.

[0351] Embodiment FF The coating composition according to embodiment EU, wherein the coating composition is present in the form of a solid phase of a solvent dispersion with a solid content from about 15.0 % to about 60.0 % by weight, wherein the solvent is an aqueous solvent, an organic solvent, or a combination thereof.

[0352] Embodiment FG The coating composition according to embodiment EU, wherein the coating composition is used for coating oral solid dosage forms selected from the group consisting of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.

[0353] Embodiment FH A coating composition for a pharmaceutical tablet comprising:(i) the reaction product of embodiment DA; and(ii) at least one ingredient selected from the group consisting of a surfactant, a film forming agent, a plasticizer, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.Docket No.: 4478PCT

[0354] While the compositions and methods of the disclosed and / or claimed inventive concept(s) have been described in terms of particular aspects, it will be apparent to those of ordinary skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the disclosed and / or claimed inventive concept(s). All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the disclosed and / or claimed inventive concept(s).

Claims

Docket No.: 4478PCTWe claim:

1. An oral solid dosage (OSD) composition comprising a reaction product of:(i) a maleated natural oil comprising a natural oil with maleated functionality; and (ii) at least one functionalized or unfunctionalized moiety selected from the group consisting of hydrophilic moieties, hydrophobic moieties, and combinations thereof.

2. The oral solid dosage composition according to claim 1, wherein the maleated natural oil is selected from the group consisting of maleated avocado oils, maleated coconut oils, maleated corn oils, maleated cottonseed oils, maleated jojoba oils, maleated linseed oils, maleated nut oils, maleated olive oils, maleated palm oils, maleated raisin oils, maleated rapeseed oils, maleated safflower oils, maleated sesame oils, maleated soybean oils, maleated squash oils, maleated sunflower oils, maleated almond oils, maleated canola oils, maleated flaxseed oils, maleated grapeseed oils, maleated palm kernel oils, maleated peanut oils, maleated walnut oils, maleated chickpea oils, maleated clary sage oils and mixtures thereof.

3. The oral solid dosage composition according to claim 2, wherein the maleated natural oil is a maleated soybean oil.

4. The oral solid dosage composition according to claim 1, wherein the functionalized or unfunctionalized moiety is a hydrophobic moiety selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof.

5. The oral solid dosage composition according to claim 4, wherein the hydrophobic alcohol or hydrophobic amine is a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl alcohol or amine.

6. The oral solid dosage composition according to claim 5, wherein the hydrophobic alcohol is selected from the group consisting of hexanol, heptanol, nonanol, decanol, dodecanol, phenol, ethylbenzyl alcohol, 2-ethyl-l -hexanol, 1-octanol, 2-octanol, 2-butyl-l -octanol, 2-octyl-1 -dodecyl alcohol, 1 -tetradecanol, 2-tetradecanol, 1 -hexadecanol, 2-hexadecanol, 1 -octadecanol 3,7-dimethyl-l-octanol, 2-propyl-l -pentanol, 4-methyl-l -pentanol, cetyl alcohol, stearyl alcohol, eicosanol, behenyl alcohol, and combinations thereof.Docket No.: 4478PCT7. The oral solid dosage composition according to claim 6, wherein the hydrophobic alcohol is behenyl alcohol.

8. The oral solid dosage composition according to claim 5, wherein the hydrophobic amine is selected from the group consisting of benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecyl amine, undecylamine, pentadecylamine, 2-methyl-butylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

9. The oral solid dosage composition according to claim 4, wherein the silicon-based compound is selected from the group consisting of aminopropylmethylsiloxane-dimethylsiloxane, N-ethylaminoisobutyl terminated polydimethylsiloxane, poly(1,1-dimethylsilazane) telomer, aminopropyl terminated polydimethylsiloxane, monoaminopropyl terminated poly dimethylsiloxane, (tetramethylpiperidinyloxy)propylmethylsiloxane)-dimethylsiloxane copolymer, polydimethylsiloxane, carbinol (hydroxyl) terminated polydimethylsiloxane, monocarbinol terminated polydimethylsiloxane, monocarbinol terminated functional polydimethylsiloxane, [Bis(hydroxyethyl)amine] terminated polydimethylsiloxane, silanol terminated polydimethylsiloxane, silanol terminated polydiphenylsiloxane, dodecylmethylsiloxane-hydroxypolyalkyleneoxypropyl methylsiloxane, and combinations thereof.

10. The oral solid dosage composition according to claim 1, wherein the functionalized or unfunctionalized moiety is a hydrophilic moiety selected from the group consisting of hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether amine monoalkyl ethers, hydrophilic polyether alcohol monoaryl ethers, hydrophilic polyether amine monoaryl ethers, hydrophilic polyether alcohol monoalkaryl ethers, hydrophilic polyether amine monoalkaryl ethers and combinations thereof.

11. The oral solid dosage composition according to claim 10, wherein the hydrophilic polyether alcohol monoalkyl ether is selected from the group consisting of polyethylene glycol monomethyl ethers, polyethylene glycol monoethyl ethers, polypropylene glycol monomethyl ethers, polypropylene glycol monoethyl ethers, poly(ethylene glycol-co-propylene glycol)Docket No.: 4478PCTmonomethyl ethers, poly(ethylene glycol-co-propylene glycol) monoethyl ethers, and combinations thereof.

12. The oral solid dosage composition according to claim 11, wherein the hydrophilic polyether alcohol monoalkyl ether is polyethylene glycol monomethyl ether.

13. The oral solid dosage composition according to claim 11, wherein the hydrophilic polyether alcohol monoalkyl ether has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons.

14. The oral solid dosage composition according to claim 13, wherein the hydrophilic polyether alcohol monoalkyl ether has a weight average molecular weight ranging from about 2,000 Daltons to about 4,000 Daltons.

15. The oral solid dosage composition according to claim 10, wherein the hydrophilic poly ether amine monoalkyl ether and hydrophilic poly ether amine monoaralkyl ether comprise one or more structures selected from the following group of structures:Me or Et, wherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

16. The oral solid dosage composition according to claim 1, wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

17. The oral solid dosage composition according to claim 16, wherein the additional hydrophilic moiety is selected from the group consisting of hydrophilic polyether glycols, hydrophilic polyether alcohol monoalkyl ethers, hydrophilic polyether polyamines, hydrophilic polyether amine monoalkyl ethers, and combinations thereof.Docket No.: 4478PCT18. The oral solid dosage composition according to claim 17, wherein- the hydrophilic polyether alcohol monoalkyl ether is selected from the group consisting of polyethylene glycol monomethyl ethers, polyethylene glycol monoethyl ethers, polypropylene glycol monomethyl ethers, polypropylene glycol monoethyl ethers, poly(ethylene glycol-co-propylene glycol) monomethyl ethers, polyethylene glycol-co-propylene glycol) monoethyl ethers, and combinations thereof; and- the hydrophilic polyether glycol is selected from the group consisting of polyethylene glycol, polypropylene glycol, poly(ethylene glycol-co-propylene glycol), and combinations thereof.

19. The oral solid dosage composition according to claim 18, wherein- the hydrophilic polyether alcohol monoalkyl ether is polyethylene glycol monomethyl ether; and- the hydrophilic polyether glycol is polyethylene glycol.

20. The oral solid dosage composition according to claim 18, wherein the hydrophilic polyether alcohol monoalkyl ether or hydrophilic polyether glycol has a weight average molecular weight ranging from about 1,000 Daltons to about 6,000 Daltons.

21. The oral solid dosage composition according to claim 20, wherein the hydrophilic poly ether alcohol monoalkyl ether or hydrophilic poly ether glycol has a weight average molecular weight ranging from about 2,000 Daltons to about 4,000 Daltons.

22. The oral solid dosage composition according to claim 17, wherein the additional hydrophilic polyether amine monoalkyl ether and hydrophilic polyether amine monoaralkyl ether comprise one or more structures selected from the following group of structures:Docket No.: 4478PCTMe or Et, wherein R is hydrogen or methyl, x and y are independently integers from about 1 to about 150, Me is methyl, Et is ethyl, and f is an integer from about 13 to about 14.

23. The oral solid dosage composition according to claim 16, wherein the additional hydrophobic moiety is selected from the group consisting of hydrophobic alcohols, hydrophobic amines, silicon-based compounds, and combinations thereof.

24. The oral solid dosage composition according to claim 23, wherein the hydrophobic alcohol or hydrophobic amine is a linear or branched, substituted or unsubstituted alkyl, cycloalkyl, alkenyl, aryl, alkaryl, or aralkyl alcohol or amine.

25. The oral solid dosage composition according to claim 24, wherein the hydrophobic alcohol is selected from the group consisting of hexanol, heptanol, nonanol, decanol, dodecanol, phenol, ethylbenzyl alcohol, 2-ethyl-l -hexanol, 1-octanol, 2-octanol, 2-butyl-l -octanol, 2-octyl-1 -dodecyl alcohol, 1 -tetradecanol, 2-tetradecanol, 1 -hexadecanol, 2-hexadecanol, 1 -octadecanol 3,7-dimethyl-l-octanol, 2-propyl-l -pentanol, 4-methyl-l -pentanol, cetyl alcohol, stearyl alcohol, eicosanol, behenyl alcohol, and combinations thereof.

26. The oral solid dosage composition according to claim 25, wherein the hydrophobic alcohol is behenyl alcohol.

27. The oral solid dosage composition according to claim 24, wherein the hydrophobic amine is selected from the group consisting of benzylamine, cyclohexylamine, hexylamine, methylhexylamine, phenethylamine, octylamine, oleylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, octadecylamine, undecylamine, pentadecylamine, 2-methylbutylamine, 1-eicosanamine, 1-docosanamine, and combinations thereof.

28. The oral solid dosage composition according to claim 23, wherein the silicon-based compound is selected from the group consisting of aminopropylmethylsiloxane-dimethylsiloxane, N-ethylaminoisobutyl terminated poly dimethyl siloxane, poly(1,1-dimethylsilazane) telomer, aminopropyl terminated polydimethylsiloxane, monoaminopropyl terminatedDocket No.: 4478PCTpolydimethylsiloxane, (tetramethylpiperidinyloxy)propylmethylsiloxane]-dimethylsiloxane copolymer, polydimethylsiloxane, carbinol (hydroxyl) terminated polydimethylsiloxane, monocarbinol terminated polydimethylsiloxane, monocarbinol terminated functional polydimethylsiloxane, [Bis(hydroxyethyl)amine] terminated polydimethylsiloxane, silanol terminated polydimethylsiloxane, silanol terminated polydiphenylsiloxane, dodecylmethylsiloxane-hydroxypolyalkyleneoxypropyl methylsiloxane, and combinations thereof.

29. The oral solid dosage composition according to claim 1, wherein the composition comprises a reaction product of:(i) a maleated soybean oil; and(ii) behenyl alcohol or polyethylene glycol monomethyl ether, or combinations thereof.

30. The oral solid dosage composition according to claim 29, wherein the composition further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

31. The oral solid dosage composition according to claim 1, wherein the composition comprises a reaction product of:(i) a maleated soybean oil;(ii) behenyl alcohol; and(iii) polyethylene glycol monomethyl ether.

32. The oral solid dosage composition according to claim 31, wherein the reaction product further comprises at least one additional moiety selected from the group consisting of additional hydrophilic moieties, additional hydrophobic moieties, and combinations thereof.

33. The oral solid dosage composition according to claim 1, wherein the reaction product comprises one or more structures selected from the following group of structures:Docket No.: 4478PCT, wherein n is integer from about 20 to about 200, or from about 40 to about 100, and Me is methyl.

34. The oral solid dosage composition according to claim 1, wherein the oral solid dosage composition further comprises at least one ingredient selected from the group consisting of an active pharmaceutical ingredient, a fdler, a binder, a surfactant, a disintegrating agent, a lubricant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

35. The oral solid dosage composition according to claim 34, wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides.

36. The oral solid dosage composition according to claim 34, wherein the filler is selected from the group consisting of monosaccharides, disaccharides, polysaccharides, inorganic acid salts, and combinations thereof.Docket No.: 4478PCT37. The oral solid dosage composition according to claim 36, wherein the filler is selected from the group consisting of cellulose, lactose, sucrose, sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, calcium sulfate, Bentonite, Kaolin, calcium diphosphate dihydrate and hydrosulfates, microcrystalline cellulose, and combinations thereof.

38. The oral solid dosage composition according to claim 34, wherein the binder is selected from the group consisting of polyvinyl pyrrolidone, starch, pregelatinized starch, gum arabic, tragacanth gum, guar gum, pectin, wax-based binders, polyethylene oxide, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and combinations thereof.

39. The oral solid dosage composition according to claim 34, wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

40. The oral solid dosage composition according to claim 34, wherein the disintegrating agent is selected from the group consisting of crospovidone, crosscarmellose sodium, low substituted hydroxypropyl cellulose, sodium starch glycolate, and combinations thereof.

41. The oral solid dosage composition according to claim 34, wherein the lubricant is selected from the group consisting of calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, palmitic acid, calcium silicate, mineral oils, bees wax, carnauba wax, hydrogenated vegetable oils, glyceryl behenate, sodium stearyl fumarate, and combinations thereof.

42. The oral solid dosage composition according to claim 34, wherein the film forming agent is selected from the group consisting of cellulose ethers, synthetic polymers, sugars, and combinations thereof.

43. The oral solid dosage composition according to claim 42, wherein the cellulose ether is selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), carboxymethyl cellulose (CMC), and combinations thereof; the synthetic polymer is selected from the group consisting of polyvinylpyrrolidone (PVP), copovidone, polyvinyl alcohol, polyethylene oxide, ethylene glycol and vinyl alcohol graft copolymer, and combinations thereof; and the sugar is selected from theDocket No.: 4478PCTgroup consisting of polydextrose, maltodextrin, sucrose, dextrose, lactose, and combinations thereof.

44. The oral solid dosage composition according to claim 34, wherein the colorant includes at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red, yellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.

45. The oral solid dosage composition according to claim 34, wherein the anti-tacking agent or the glidant is selected from the group consisting of talc, silica, medium chain triglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof.

46. The oral solid dosage composition according to claim 34, wherein the plasticizer is selected from the group consisting of propylene glycol, glycerol, polyethylene glycols (200-6000), citrate esters, glyceryl triacetate, dibutyl sebacate, phthalate esters, acetylated monoglycerides, castor oil, mineral oil, and combinations thereof47. The oral solid dosage composition according to claim 1, wherein the reaction product is present in an amount from about 5.0 wt.% to about 70.0 wt.% of the total oral solid dosage composition.

48. The oral solid dosage composition according to claim 34, wherein the ingredient is present in an amount from about 0.1 wt.% to about 95.0 wt.%> of the total oral solid dosage composition.

49. The oral solid dosage composition according to claim 34, wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.

50. The oral solid dosage composition according to claim 49, wherein the oral solid dosage composition is a coated oral solid dosage composition.Docket No.: 4478PCT51. The oral solid dosage composition according to claim 50, wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition.

52. The oral solid dosage composition according to claim 51, wherein the coated pharmaceutical composition is a dry film coated OSD composition, an immediate release coated OSD composition, a delayed release coated OSD composition, or a modified release coated OSD composition.

53. A granule composition comprising:(i) the reaction product of claim 1; and (ii) at least one active pharmaceutical ingredient.

54. The granule composition according to claim 53, wherein the reaction product is functioning as a binding agent.

55. The granule composition according to claim 53, wherein the active pharmaceutical ingredient is selected from the group consisting of BCS class I to BCS class IV drugs including proteins, peptides, and macrocyclic peptides.

56. The granule composition according to claim 53, wherein the reaction product is present in an amount from about 5.0 wt.% to about 20.0 wt. % of the total granule composition weight.

57. The granule composition according to claim 53, wherein the active pharmaceutical ingredient is present in an amount from about 80.0 wt.% to about 95.0 wt.% of the total granule composition weight.

58. An oral solid dosage composition comprising:(i) the granule composition of claim 53; and(ii) at least one additional ingredient.

59. The oral solid dosage form according to claim 58, wherein the additional ingredient is selected from the group consisting of a filler, an additional binder, a surfactant, a disintegrating agent, a lubricant, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.Docket No.: 4478PCT60. The oral solid dosage composition according to claim 59, wherein the filler is selected from the group consisting of monosaccharides, disaccharides, polysaccharides, inorganic acid salts, and combinations thereof.

61. The oral solid dosage composition according to claim 60, wherein the filler is selected from the group consisting of cellulose, lactose, sucrose, sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, calcium sulfate, Bentonite, Kaolin, calcium diphosphate dihydrate and hydrosulfates, microcrystalline cellulose, and combinations thereof.

62. The oral solid dosage composition according to claim 59, wherein the additional binder is selected from the group consisting of polyvinyl pyrrolidone, starch, pre-gelatinized starch, gum arabic, tragacanth gum, guar gum, pectin, wax-based binders, polyethylene oxide, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and combinations thereof.

63. The oral solid dosage composition according to claim 59, wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

64. The oral solid dosage composition according to claim 59, wherein the disintegrating agent is selected from the group consisting of crospovidone, crosscarmellose sodium, low substituted hydroxypropyl cellulose, sodium starch glycolate, and combinations thereof.

65. The oral solid dosage composition according to claim 59, wherein the lubricant is selected from the group consisting of calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, palmitic acid, calcium silicate, mineral oils, bees wax, carnauba wax, hydrogenated vegetable oils, glyceryl behenate, sodium stearyl fumarate, and combinations thereof.

66. The oral solid dosage composition according to claim 59, wherein the colorant includes at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red,Docket No.: 4478PCTyellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.

67. The oral solid dosage composition according to claim 59, wherein the anti-tacking agent or the glidant is selected from the group consisting of talc, silica, medium chain triglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof.

68. The oral solid dosage composition according to claim 58, wherein the granule composition is present in an amount from about 50.0 wt.% to about 90.0 wt.% of the total oral solid dosage composition.

69. The oral solid dosage composition according to claim 58, wherein the additional ingredient is present in an amount from about 10.0 wt. % to about 50.0 wt. % of the total oral solid dosage composition.

70. The oral solid dosage composition according to claim 58, wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.

71. The oral solid dosage composition according to claim 70, wherein the oral solid dosage composition is a coated oral solid dosage composition.

72. The oral solid dosage composition according to claim 71, wherein the coated oral solid dosage composition is a coated nutritional composition, a coated dietary supplement composition, or a coated pharmaceutical composition.

73. The oral solid dosage composition according to claim 72, wherein the coated pharmaceutical composition is a dry-film coated OSD composition, an immediate-release coated OSD composition, a delay ed-release coated OSD composition, or a modified-release coated OSD composition.

74. A coating composition for an oral solid dosage form comprising:(i) the reaction product of claim 1; and(ii) at least one ingredient.Docket No.: 4478PCT75. The coating composition according to claim 74, wherein the ingredient is selected from the group consisting of a surfactant, a film forming agent, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

76. The coating composition according to claim 75, wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, Polysorbates 20-80, Span 20-80, Poloxamers, and combinations thereof.

77. The coating composition according to claim 75, wherein the film forming agent is selected from the group consisting of cellulose ethers, synthetic polymers, sugars, and combinations thereof.

78. The coating composition according to claim 77, wherein the cellulose ether is selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), carboxymethyl cellulose (CMC), and combinations thereof; the synthetic polymer is selected from the group consisting of polyvinylpyrrolidone (PVP), copovidone, polyvinyl alcohol, ethylene glycol and vinyl alcohol graft copolymer, and combinations thereof; and the sugar is selected from the group consisting of polydextrose, maltodextrin, sucrose, dextrose, lactose, and combinations thereof.

79. The coating composition according to claim 75, wherein the colorant includes at least one pigment, dye or lake selected from the group consisting of FD& C Blue #1, FD& C Blue #2, FD& C Red #40, FD& C Yellow #5, FD& C Yellow #6, D& C Red #27, carmine, saffron, riboflavin, caramel, carmosine, beta-carotene, Patent Blue V, Ponceau 4R, curcumin, Quinoline Yellow, red cabbage extract, titanium dioxide, calcium carbonate, iron oxides (red, yellow & black), zinc oxide, magnesium carbonate, dicalcium phosphate, sodium copper chlorophyllin, mica-based pearlescent pigments, carbon black, and combinations thereof.

80. The coating composition according to claim 75, wherein the anti-tacking agent or the glidant is selected from the group consisting of talc, silica, medium chain triglycerides, lecithin, glyceryl monostearate, glyceryl monocaprylocaprate, and combinations thereof81. The oral solid dosage composition according to claim 75, wherein the plasticizer is selected from the group consisting of propylene glycol, glycerol, polyethylene glycols (200-6000),Docket No.: 4478PCTcitrate esters, glyceryl triacetate, dibutyl sebacate, phthalate esters, acetylated monoglycerides, castor oil, mineral oil, and combinations thereof.

82. The coating composition according to claim 74, wherein the reaction product is present in an amount from about 5.0 wt.% to about 70.0 wt.% of the total coating composition weight.

83. The coating composition according to claim 74, wherein the ingredient is present in an amount from about 30.0 wt.% to about 95.0 wt.% of the total coating composition weight.

84. The coating composition according to claim 74, wherein the coating composition is present in the form of a dry powder.

85. The coating composition according to claim 74, wherein the coating composition is present in the form of a solid phase of a solvent dispersion with a solid content from about 15.0 % to about 60.0 % by weight, wherein the solvent is an aqueous solvent, an organic solvent, or a combination thereof.

86. The coating composition according to claim 74, wherein the coating composition is used for coating oral solid dosage forms selected from the group consisting of a tablet, a minitablet, a capsule, powder, granules, multi particulates, lozenges, and candies.

87. A coating composition for a pharmaceutical tablet comprising:(i) the reaction product of claim 1; and(ii) at least one ingredient selected from the group consisting of a surfactant, a film forming agent, a plasticizer, a colorant, an anti-tacking agent or a glidant, a plasticizer, a flavor, a sweetener, and combinations thereof.

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