WO2005087202A1

WO2005087202A1 - Glucosamine polyacrylate inter-polymer complex and processes for their production

Info

Publication number: WO2005087202A1
Application number: PCT/IB2004/000336
Authority: WO
Inventors: Gour Mukherji; Clive George Wilson; Ashok Rampal; Ravikumar Nithiyanandam; Mahendra Ramachandra Joshi
Original assignee: Ranbaxy Laboratories Limited
Priority date: 2004-02-10
Filing date: 2004-02-10
Publication date: 2005-09-22

Abstract

The present invention is related to granulation processes for making a solid, particulate complex formed by the inter-polymer complexation of a cationic polymeric glucosamine or its derivatives and an anionic, cross-linked, polyacrylic acid or its derivatives.

Description

GLUCOSAMINE POLYACRYLATE INTER-POLYMER COMPLEX AND PROCESSES FOR THEIR PRODUCTION Technical Field of the Invention The present invention is related to granulation methods for making a solid, particulate complex formed by the inter-polymer complexation of a cationic polymeric glucosamine or its derivatives and an anionic, cross-linked, polyacrylic acid or its derivatives. Background of the Invention Complexes of cationic polymers have been prepared with different polyanions including synthetic polyanions (e.g., polyacrylic, polymethacryhc acids and polyvinyl alcohol sulphate); natural polyanions (e.g., alginate, derivatives), carboxymethylcellulose and oxidized cellulose. Complexes of natural polyions, such as chitosan, carboxymethylcellulose and alginic acid, are known in the art. Polyion, inter-polymer complexes are ionically cross-linked hydrogels formed by the co-reaction interaction of oppositely charged macromolecules. The process of complexation is a useful method to generate polymer systems that are linked to interacting reactants without any strong bond formation. Instead, the link between the reactants is formed by means of weak secondary binding forces, such as electrostatic interaction, hydrogen bonding, and Nan der Waals forces, among others. The inter-polymer complex can synergize the individual properties of the interacting polymers by increasing the intensity of any one or more of their individual properties. Alternatively, this synergism may be found in the separate manifestation in the complex of many of the properties of the interacting polymers. U.S. Patent No. 5,510,418 describes biocompatible, biologically inert conjugates that include a chemically derived glycosaminoglycan chemically conjugated to a synthetic hydrophilic polymer, namely, polyethylene glycol. The chemical conjugation may be formed by a variety of types of covalent linkages, including ether and ester linkages. U.S. Patent No. 3,962,158 describes hydrophilic polymer membranes useful as semi- permeable membranes or ultra filter membranes. These membranes are manufactured by forming a film from an aqueous solution containing polyvinyl alcohol and a chitosan salt and then subjecting the film to an alkali treatment. U.S. Patent No. 4,501,835 describes a composition of matter that is a complex of polyacrylic acid and chitosan, the molecular weight of the polyacrylic acid being less than about 10,000. The complex is prepared by combining, with mixing, an acidic solution of low molecular weight polyacrylic acid and an acidic solution of chitosan. The complex is described as being employed to form membranes and films. U.S. Patent No. 4,956,170 discloses a high alcohol content skin moisturizing/conditioning antimicrobial gel. The gel includes from about 60-75 weight percent of ethanol and from about 0.4 to 2 weight percent of a thickening agent which is an addition polymer of acrylic acid cross-linked with an unsaturated polyfunctional agent. U.S. Patent No. 5,167,950 describes a high alcohol content aerosol antimicrobial mousse composition that is made from water-dispersible, polymeric gelling agents. The gelling agent described as being preferably employed is an addition polymer of acrylic acid cross-linked with an unsaturated polyfunctional agent, such a polyalkyl ether of sucrose. Summary of the Invention In one general aspect there is provided a process for preparing an inter polymer complex composition. The process includes wetting a polymeric glucosamine or its derivatives with a first solvent to form a first hydrated blend; wetting a cross-linked polyacrylic acid or its derivatives with a second solvent to form a second hydrated blend; blending the first and the second hydrated blends; and drying the blend. Embodiments of the process may include one or more of the following features. For example, the polymeric glucosamine may be a chitosan or its derivatives. The chitosan may be one or more of chitosan, glycol chitosan, carboxymethyl chitosan and hydroxypropyl chitosan. The first solvent may be an aqueous media. The aqueous media may be an acidic aqueous media. The acidic aqueous media may be one or more of hydrochloric acid, formic acid, acetic acid, citric acid, ascorbic acid, lactic acid and combinations thereof. The second solvent may be an aqueous media. The second solvent may be a mixture of an aqueous media and an organic media. The organic media may be one or more of an ester, a ketone, and an alcohol. The alcohol may be one or more of ethanol, isopropyl alcohol, and absolute ethanol. The cross-linked polyacrylic acid or its derivatives may be a homopolymer and a copolymer or a homopolymer. The cross-linked polyacrylic acid or its derivatives may have a molecular weight of greater than about 2 billion Dalton. The ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivative may be at least about 1 :30, particularly between about 1:15 and about 15:1, and more particularly at least about 1:3. The process may further include placing the dried blend in an aqueous media at a pH of more than 3 and measuring an uptake of the aqueous media in the dried blend, wherein the uptake of the aqueous media in the dried blend is between about 10 to about 75 times the weight of the dried blend. In the process, wetting the cross-linked polyacrylic acid or its derivatives with the second solvent to form a second hydrated blend may include adding the cross-linked polyacrylic acid to the first hydrated blend. Wetting the polymeric glucosamine or its derivatives with the first solvent to form a first hydrated blend may include adding the polymeric glucosamine to an acid and then adding water to the mixture of glucosamine and acid. The process may further include milling the dried blend to form a milled material. The process may further include mixing the milled material with either or both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients. The process may further include forming a final dosage form. The process may further include adding either of both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients and forming a final dosage form. In another general aspect there is provided a process for preparing an inter polymer complex composition. The process includes blending a polymeric glucosamine or its derivatives with a cross-linked polyacrylic or its derivatives in the dry state to form a blend; granulating the blend with an acidified aqueous solvent to form granulates; and drying the blend. Embodiments of the process may include one or more of the following features. For example, the polymeric glucosamine may be a chitosan or its derivatives. The cliitosan may be one or more of chitosan, glycol chitosan, carboxymethyl chitosan and hydroxypropyl chitosan. The acidified aqueous solvent may be one or more of hydrochloric acid, formic acid, acetic acid, citric acid, ascorbic acid, lactic acid and combinations thereof. The process may further include adding an organic solvent. The organic solvent may be one or more of an ester, a ketone, and an alcohol. The alcohol may be one or more of ethanol, isopropyl alcohol, and absolute ethanol. The cross-linked polyacrylic acid or its derivatives may be a homopolymer and a copolymer, or a homopolymer. The cross-linked polyacrylic acid or its derivatives may have a molecular weight of greater than about 2 billion Dalton. The ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivative may be at least about 1:30, particularly may be between about 1:15 and about 15:1, and more particularly may be at least about 1:3. The process may further include placing the dried blend in an aqueous media at a pH? of more than 3 and measuring an uptake of the aqueous media in the dried blend, wherein the uptake of the aqueous media in the dried blend is between about 10 to about 75 times the weight of the dried blend. The process may further include milling the dried blend to form a milled material and may still further include mixing the milled material with either or both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients. The process may further include forming a final dosage form. The process may further include adding either of both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients and forming a final dosage form. In another general aspect, a pharmaceutical composition includes a granulated inter-polymer complex. The granulated inter-polymer complex includes a polymeric glucosamine or its derivative; and a cross-linked polyacrylic acid or its derivatives. The molecular weight of the cross-linked polyacrylic acid or its derivatives is greater than or equal to 700,000 Daltons. The uptake of an aqueous media in the complex is between about 10 to about 75 times the weight of the complex when the complex is placed in an aqueous media at a pH? of more than 3. Embodiments of the pharmaceutical composition may include one or more of the following features. For example, the composition may further include one or more active pharmaceutical agents. The pharmaceutical composition may further include one or more pharmaceutically acceptable excipients. The one or more pharmaceutically acceptable excipients may be one or more of diluents, binders, disintegrants, swelling agents, fillers, coloring agents, flavoring agents, stabilizers, surfactants, lubricants, glidants, plasticizers and preservatives. The details of one or more embodiments of the inventions are set forth in the description below. Other features, objects and advantages of the inventions will be apparent from the description and claims. Detailed Description of the Invention The inventors have developed new processes useful for preparing solid, particulate complexes formed by an inter-polymer complexation of a cationic polymeric glucosamine or its derivatives and an anionic cross-linked, polyacrylic acid or its derivatives. The improvements described herein relate to (1) a considerable reduction in the quantities of solvents used for the complex formation, and (2) the use of a mixer for manufacturing. The inventors have previously described a process of complexation that is disclosed in copending application PCT/U302/01708, titled Glucosamine Polyacrylate Inter-Polymer Complex and Applications Thereof. This previously disclosed process of complexation generally involves interacting a colloidal dispersion of cross-linked polyacrylic acid or its derivatives with an aqueous solution of a cationic polymeric glucosamine or its derivatives. A hydroethanolic solvent system is used for dispersing cross-linked polyacrylic acid. The new processes described herein involve blending by a wet granulation method using considerably lower quantities of solvents. The granulation can be effectively carried out in a mixer thus making the complexation process simpler and cost-effective. A hydrogel is a cross-linked polymer network that is insoluble in water but swells to an equilibrium size in the presence of excess water. Due to the unique properties of hydrogels and their potential applications in areas such as controlled drug delivery, various types of hydrogels have been synthesized and characterized. In certain applications, the complex of polymeric glucosamine and cross-linked polyacrylic acid forms a hydrogel. These two components are described in more detail below. Glucosamine, which is 2-amino-2-deoxy-alpha-D-glucose, occurs widely in nature; in the body it may be isolated as glucosamine 6-phosphate. It is one of the two hexosamine sugars (6-carbon amino sugars) common in animal cells. A glucosamine polymer that is of particular relevance to this application is the semi-synthetic material isolated from chitin, namely, chitosan. Chitosan is poly-[I- 4]-beta-D- glucosamine and is a partially deacetylated chitin. As referred to herein, it is acid soluble and has at least 75% degree of deacetylation. It may contain less than 15% acetylated residues from chitin. Other polyglucosamines include but are not limited to carboxymethyl chitosan, hydroxypropyl chitosan, and glycol chitosan. Cross-linked polyacrylic acid or its derivatives, as referred to in this application, include water-swellable, high molecular weight, cross-linked homopolymers and copolymers which form hydrogels in aqueous solution. The cross-linker types and levels can be modified, as well as the amounts and characteristics of the hydrophobic co- monomers. Commercial grades of cross-linked polyacrylic acid are available from Noveon (formerly, BF Goodrich) as Carbopol®, Pemulen®, and Noveon® resins. Specifically, the resins are (i) homopolymers of acrylic acid cross-linked with allyl sucrose or allyl pentaerythritol (Carbopol® homopolymers), (ii) homopolymers of acrylic acid cross-linked with divinyl glycol (Noveon® polycarbophils), and (iii) copolymers of acrylic acid with minor levels of long chain alkyl acrylate co-monomers cross-linked with allylpentaerythritol (Carbopol® copolymers and Pemulen® polymeric emulsifiers). The molecular weight of these polymers is estimated to range from approximately 700,000 to approximately 3 or 4 billion. They swell in water and entrap up to approximately 1000 times their original volume to form a gel when exposed to a pH environment above 4-6. Since the pKa of these polymers is 6±0.5, the carboxylate groups on the polymer backbone ionize, resulting in repulsion between the negatively charged groups, which adds to the swelling of the polymer. Cross-linked polymers do not dissolve in water. Non-aqueous gels are stable gels with a wide range of hardness and stability over a wide range of pH conditions. These gels utilize an anhydrous liquid component extending their usefulness into many areas not suited for the use of water-based gel systems. The gellants used are in the form of alkyl amides of di- and/or tri-basic carboxylic acids or anhydrides. The gellant materials are produced by reacting the di- or tri-basic organic acid or anhydride, or the methyl ester form thereof, with the desired alkyl amine. This gel- based technology makes use of an anhydrous or semi-hydrous liquid carrier. One such non-aqueous gel is the hydroalcoholic hand sanitizing gels that have found increasing use due to their ability to instantly kill germs and bacteria without the use of soap and water and their pleasant after-feel on the hands owing to conditioning and moisturizing benefits. Carbopol® polymers are preferred in these hydroalcohohc gels. The key to formulating such hydroalcohohc gels with Carbopol® polymers is choosing the correct neutralizing agents that are effective at the low levels of water in these systems. The inventors have found that higher alcohol content in the solvent system is highly desirable during neutralization as the alcohol level is important for the unique swelling and water absorption characteristics exhibited by the inter-polymer complexes of the present invention. Commonly used neutralizing agents which can accommodate higher alcohol content in the solvent system are generally not recommended for oral use. Such neutralizing agents include triethanolamine (30% w/w), tromethamine (60% w/w), aminomethylpropanol, triisopropanolamine, diisopropanolamine and tetrahydroxypropylethylenediamine (all 80% w/w), PEG-15 cocoamine (>90% w/w). The inventors have found through extensive experimentation that polyglucosamines, particularly chitosan or its derivatives, are good neutralizing agents for cross-linked polyacrylic acids and, advantageously, the resultant complexes are suitable for oral administration. The interaction of cross-linked polyacrylic acid with chitosan or its derivatives in hydro-organic media generally produces stronger gels than the same interaction in a completely aqueous media. The preparation of the complex in water rather than a hydro- alcoholic solvent, followed by drying, results in viscous solutions on interaction of the dry powder with buffers. This generally decreases both the extent of swelling and the strength of the swollen mass. When a proportion of the water is replaced by an organic solvent during processing a different type of gel complex forms, which becomes evident upon hydrating the dry powder. As little as about 5% v/v organic solvent will result in a change in gel strength and, generally, the higher the level of the organic solvent the greater the extent of structuring. The level of organic solvent may be, for example, as high as between about 70% and about 90%. The complexation process involves neutralization of anionic functional groups in cross-linked polyacrylic acid with cationic functional groups in polyglucosamine or its derivatives. The ratios of the interacting species (i.e., polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivatives) can vary between 1:30 and 30:1. In practice, the ratio should be at least 1:15 and the most preferred ratio of the interacting species ingredients is at least 1:3. The resulting complex at neutralization has water absorbing capacity (at pH greater than 3) of a very high magnitude and results in a highly swollen and structured gel. The rate of formation of the swollen gel is very fast and complete hydration occurs well within five minutes. The inventors have developed two processes for blending the two interacting polymers. In the first process, the two gel forming polymers are blended in the dry state and then the blend is granulated using a non-aqueous solvent. In the second process, the two gel forming polymers are separately wetted with suitable solvents and then blended, hi summary, according to one process, the two gel forming polymers are wetted separately with suitable solvents, mixed, and blended to obtain the desired consistency. The blended mass then is dried to a constant weight and milled to a suitable size. Of course, one of the gel forming polymers can be wetted first and then the second gel forming polymer added. According to another process, the two gel forming polymers are blended in the dry state and the resulting blend is granulated using suitable solvents. The wet mass then is dried to a constant weight and milled to a suitable size. The mass or gel is dried by any suitable drying method or process known in the art, which, includes but is not limited to, oven drying, vacuum oven drying, fluid-bed drying, freeze drying, spray drying and microwave oven drying. The dried material is milled to a suitable size to obtain the complex as a dry, particulate solid material. The complex will form a highly swollen gel when placed in an aqueous media at a pH? of more than 3 and entrap 10 to 75 times its own mass of the solvent. hi forming the complex, various solvents can be used with the glucosamine and the polyacrylic acid. For example, a preferred solvent for glucosamine or its derivatives appears to be an aqueous solution. Depending upon solubility properties, the glucosamine under consideration may be wetted with an acidified solution. The acids preferred for this purpose include but are not limited to sulphuric acid, hydrochloric acid, formic acid, acetic acid, lactic acid, ascorbic acid, citric acid and combinations thereof. Similarly, polyacrylic acid may be dispersed in an aqueous media as a colloidal hydrogel or as a particulate dispersion in an organic solvent, such as an ester or a ketone. Suitable organic solvents for polyacrylic acid include ethanol, isopropyl alcohol and acetone. A very suitable solvent for polyacrylic acid is absolute ethanol. IR spectroscopy in KBr disc of both the interacting polymers individually and the resultant complex shows no evidence suggesting formation of any covalent linkage involving ether or ester bonds. The solid material obtained, as described in the processes below, has been evaluated for its degree of swelling in buffers of pH 7.5, which is an evaluation of its media absorption capacity. Simultaneously, the texture characteristics of the swollen gels in this medium have also been evaluated. The texture profiles of the reactants were found to be very different from the complex. The texture profiles were obtained using the Texture Expert Exceed (Stable Micro Systems, UK), which is a versatile instrument for measuring the texture of materials. It has applications in the pharmaceutical, cosmetic, food and packaging industries. By suitable selecting tooling, probes, and parameter settings, a wide range of materials can be evaluated for their texture properties. The properties which can be measured in a gel include firmness, stiffness, resilience and stickiness. Using a cylindrical probe in a compression mode, the work of resistance during the penetration of the probe into the gel and the work of resilience as the probe withdraws, can be measured. As described below, the gels which have been prepared as described herein have been characterized and differentiated by means of the texture analyzer. The texture analyzer, Model-XT2i, was fitted with a load cell with an operating maximum of 5 kg. Using a 5 mm diameter stainless steel cylinder probe, the pre-test, test and post-test speeds were 2 mm per second, 1 mm per second and 1 mm per second, respectively. The distance traveled in the gel was 10 mm. Other settings were as follows, trigger type -auto; trigger force - 0.5 g; 'Measure force in compression'; 'Return to start' an PPS -200. The gel obtained using the processes described herein can serve a number of useful functions in pharmaceutical dosage forms, including among others, as a high bulk substance for oral administration, as a matrix in oral controlled release, in taste-masking, and as a tablet disintegrant. The following examples illustrate the preparation of an interpolymer complex within the scope of the present invention and are not intended to be limiting. EXAMPLE 1 Chitosan (2.0 g) was added to acetic acid (5.0 ml) and Carbopol® 971P (2.0 g) was mixed with ethanol (2.0 ml). As such, the chitosan and the Carbopol® were wetted separately. Both then were mixed together homogeneously, which resulted in a gel mass. To this resultant gel mass 15 ml of ethanol and water in the ratio of 2:1 was added to loosen the mass and to ensure good granulation. The gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 2 Chitosan (2.0 g) was added to an acetic acid solution in water (40.0 ml). The acetic acid solution was prepared by mixing 1 part of acetic acid with 5 parts of purified water. Purified water q.s. was added to hydrate the resulting mass further. Carbopol® 971P (2.0 g) was added in small increments to the hydrated chitosan mass with continuous mixing. Ethanol (22.0 ml) was added simultaneously to loosen up the mass and facilitate granulation. The resulting gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 3 Chitosan (0.5 g) was added to acetic acid (1.0 ml). Purified water q.s. was added to hydrate the mass further. Carbopol® 971P (1.5 g) was mixed with ethanol (0.5 ml). As such, the chitosan and the Carbopol® were wetted separately. Both then were mixed together homogeneously. To the resultant gel mass purified water (q.s.) was added with continuous mixing. The gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 4 Chitosan (2.0g) and Carbopol® 971P (2.0 g) were mixed homogeneously (i.e., blended together in the dry state). The polymer mix was then granulated using a sufficient quantity of 0.1 N HCl. The gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 5 Chitosan (2.0 g) was dispersed in 0.1 N HCl (20.0 ml). Carbopol® 971P (2.0 g) was added to the acidified Chitosan solution gradually in small increments. Ethanol (15.0 ml) next was added. The gel mass then was dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 6 Chitosan (2.0 g) was dispersed in purified water (10.0 ml). 0.1 N HCl (5.0 ml) was added to the Chitosan mass. Carbopol® 971 P (2.0 g) was added in small increments to the acidified chitosan solution. Ethanol (17.0 ml) was next added to the blend. The gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 7 Chitosan (2.0 g) was added to lactic acid (8.0 ml) and mixed well. Purified water (40.0 ml) was added to form a paste of chitosan. Carbopol® 971 P (2.0 g) was added to the chitosan paste with continuous mixing. Ethanol (30.0 ml) was added to facilitate granulation. The gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 8

Chitosan (2.0 g) was blended uniformly with ascorbic acid (4.5 g). Purified Water (10.0 ml) was added to the chitosan mixture and mixed well. Carbopol® 971 P (2.0 g) was added in small increments to the hydrated chitosan and ascorbic acid mixture. Ethanol (15.0 ml) was added thereafter. The gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. EXAMPLE 9

Chitosan (4.0 g) was blended uniformly with acetic acid (10.0 ml) and lactic acid (5.0 ml). Purified water (30.0 ml) was added to hydrate the acidified chitosan. Carbopol® 971P (4.0 g) was added in small increments and mixed well. Ethanol (60.0 ml) was added thereafter to the blend. The gel mass was then dried in a hot air oven. The dried material was milled and evaluated for degree of swelling in pH 7.5 buffer. The result of the testing for each of these formulations is provided in Table I, below. As is evident from the results provided, the properties of the resulting formulations can be varied by changing the steps and solvents. Thus, formulations can be prepared using an acidic aqueous media, an ethanol media (i.e., aqueous organic media), an aqueous media, or any combination thereof. Moreover, either the chitosan or the glucosamine can be wetted first and or simultaneously, and the media can be added at various times during the process. Table 1. Degree of Swelling and Texture Data

*Because of the low degree of swelling, Example 7 was not evaluated for texture analysis Other formulations can be provided by varying the media and/or the stoichiometry. For example, an instantaneous rupture dosage form can be formulated by mixing the polyacrylic acid and the glucosamine with an acidic media, adding an active pharmaceutical ingredient, and forming the dosage form by, for example, granulation, drying and compressing, etc. A dual profile dosage form also can be formulated by varying the stoichiometry. For example, rather than using a 1.1 stoichiometric ratio of the polyacrylic acid and the glucosamine, the ratio can be 1 : 10. By mixing the 1 : 1 ratio of polyacrylic acid and glucosamine with an acid media and then adding a set quantity of the drug to form, e.g., granules, the dosage form has an instantaneous release component. The amount of drug in the instantaneous component is determined based on the drug and therapeutic effect desired. Then, to form a controlled release component the remaining nine parts of the glucosamine are mixed with, e.g., ethanol, and granulated with the remainder of the active pharmaceutical ingredient. Then, the instantaneous release component is mixed with the controlled release component to form a dual dosage profile dosage form. While several particular forms of the inventions have been described, it will be apparent that various modifications and combinations of the inventions detailed in the text can be made without departing from the spirit and scope of the inventions. Further, it is contemplated that any single feature or any combination of optional features of the inventive variations described herein may be specifically excluded from the claimed inventions and be so described as a negative limitation. Accordingly, it is not intended that the inventions be limited, except as by the appended claims.

Claims

WE CLAIM: 1. A process for preparing an inter polymer complex composition, the process comprising: wetting a polymeric glucosamine or its derivatives with a first solvent to form a first hydrated blend; wetting a cross-linked polyacrylic acid or its derivatives with a second solvent to form a second hydrated blend; blending the first and the second hydrated blends; and drying the blend.

2. The process of claim 1, wherein the polymeric glucosamine comprises a chitosan or its derivatives.

3. The process of claim 2, wherein the chitosan comprises one or more of chitosan, glycol chitosan, carboxymethyl chitosan and hydroxypropyl chitosan.

4. The process of claim 1, wherein the first solvent comprises an aqueous media.

5. The process of claim 4, wherein the aqueous media comprises an acidic aqueous media.

6. The process of claim 5, wherein the acidic aqueous media comprises one or more of hydrochloric acid, formic acid, acetic acid, citric acid, ascorbic acid, lactic acid and combinations thereof.

7. The process of claim 1, wherein the second solvent comprises an aqueous media.

8. The process of claim 1, wherein the second solvent comprises a mixture of an aqueous media and an organic media.

9. The process of claim 8, wherein the organic media comprises one or more of an ester, a ketone, and an alcohol.

10. The process of claim 9, wherein the alcohol comprises one or more of ethanol and isopropyl alcohol.

11. The process of claim 9, wherein the alcohol comprises absolute ethanol.

12. The process of claim 5 wherein the organic solvent comprises ethanol.

13. The process of claim 1 , wherein the cross-linked polyacrylic acid or its derivatives comprises a homopolymer and a copolymer.

14. The process of claim 1, wherein the cross-linked polyacrylic acid or its derivatives comprises a homopolymer.

15. The process of claim 1 , wherein the cross-linked polyacrylic acid or its derivatives has a molecular weight of greater than about 2 billion Dalton.

16. The process of claim 1, wherein the ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivative is at least about 1:30.

17. The process of claim 1, wherein the ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivatives is between about 1:15 and about 15:1.

18. The process of claim 1, wherein the ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivatives is at least about 1:3.

19. The process of claim 1, further comprising placing the dried blend in an aqueous media at a pH of more than 3 and measuring an uptake of the aqueous media in the dried blend, wherein the uptake of the aqueous media in the dried blend is between about 10 to about 75 times the weight of the dried blend.

20. The process of claim 1, wherein wetting the cross-linked polyacrylic acid or its derivatives with the second solvent to form a second hydrated blend comprise adding the cross-linked polyacrylic acid to the first hydrated blend.

21. The process of claim 1 , wherein wetting the polymeric glucosamine or its derivatives with the first solvent to form a first hydrated blend comprises adding the polymeric glucosamine to an acid and then adding water to the mixture of glucosamine and acid.

22. The process of claim 1, further comprising milling the dried blend to form a milled material.

23. The process of claim 22, further comprising mixing the milled material with either or both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients.

24. The process of claim 23, further comprising forming a final dosage form.

25. The process of claim 1, further comprising adding either of both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients and forming a final dosage form.

26. A process for preparing an inter polymer complex composition, the process comprising: blending a polymeric glucosamine or its derivatives with a cross-linked polyacrylic or its derivatives in the dry state to form a blend; granulating the blend with an acidified aqueous solvent to form granulates; and drying the blend.

27. The process of claim 26, wherein the polymeric glucosamine comprises a chitosan or its derivatives.

28. The process of claim 27, wherein the chitosan comprises one or more of chitosan, glycol chitosan, carboxymethyl chitosan and hydroxypropyl chitosan.

29. The process of claim 26, wherein the acidified aqueous solvent comprises one or more of hydrochloric acid, formic acid, acetic acid, citric acid, ascorbic acid, lactic acid and combinations thereof.

30. The process of claim 26, further comprising adding an organic solvent.

31. The process of claim 30, wherein the organic solvent comprises one or more of an ester, a ketone, and an alcohol.

32. The process of claim 31, wherein the alcohol comprises one or more of ethanol and isopropyl alcohol.

33. The process of claim 31, wherein the alcohol comprises absolute ethanol.

34. The process of claim 26, wherein the cross-linked polyacrylic acid or its derivatives comprises a homopolymer and a copolymer.

35. The process of claim 26, wherein the cross-linked polyacrylic acid or its derivatives comprises a homopolymer.

36. The process of claim 26, wherein the cross-linked polyacrylic acid or its derivatives has a molecular weight of greater than about 2 billion Dalton.

37. The process of claim 26, wherein the ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivative is at least about 1 :30.

38. The process of claim 26, wherein the ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivatives is between about 1:15 and about 15:1.

39. The process of claim 26, wherein the ratio of the polymeric glucosamine or its derivatives to the cross-linked polyacrylic acid or its derivatives is at least about 1:3.

40. The process of claim 26, further comprising placing the dried blend in an aqueous media at a pH of more than 3 and measuring an uptake of the aqueous media in the dried blend, wherein the uptake of the aqueous media in the dried blend is between about 10 to about 75 times the weight of the dried blend.

41. The process of claim 26, further comprising milling the dried blend to form a milled material.

42. The process of claim 41, further comprising mixing the milled material with either or both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients.

43. The process of claim 42, further comprising forming a final dosage form.

44. The process of claim 26, further comprising adding either of both of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients and forming a final dosage form.

45. A pharmaceutical composition comprising a granulated inter-polymer complex, the granulated inter-polymer complex comprising: a polymeric glucosamine or its derivative; and a cross-linked polyacrylic acid or its derivatives, wherein the molecular weight of the cross-linked polyacrylic acid or its derivatives is greater than or equal to 700,000 Daltons, and wherein the uptake of an aqueous media in the complex is between about 10 to about 75 times the weight of the complex when the complex is placed in an aqueous media at a pH of more than 3.

46. The pharmaceutical composition of claim 45, further comprising one or more active pharmaceutical agents.

47. The pharmaceutical composition of claim 45, further comprising one or more pharmaceutically acceptable excipients.

48. The pharmaceutical composition of claim 47, wherein the one or more pharmaceutically acceptable excipients comprise one or more of diluents, binders, disintegrants, swelling agents, fillers, coloring agents, flavoring agents, stabilizers, surfactants, lubricants, glidants, plasticizers and preservatives.