[go: up one dir, main page]

WO2003067952A2 - Complexe de glucosamine-polyacrylate inter-polymere et applications - Google Patents

Complexe de glucosamine-polyacrylate inter-polymere et applications Download PDF

Info

Publication number
WO2003067952A2
WO2003067952A2 PCT/IB2002/000415 IB0200415W WO03067952A2 WO 2003067952 A2 WO2003067952 A2 WO 2003067952A2 IB 0200415 W IB0200415 W IB 0200415W WO 03067952 A2 WO03067952 A2 WO 03067952A2
Authority
WO
WIPO (PCT)
Prior art keywords
acid
derivatives
cross
inter
polymer complex
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2002/000415
Other languages
English (en)
Other versions
WO2003067952A3 (fr
Inventor
Gour Mukherji
Clive Wilson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ranbaxy Laboratories Ltd
Original Assignee
Ranbaxy Laboratories Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ranbaxy Laboratories Ltd filed Critical Ranbaxy Laboratories Ltd
Priority to PCT/IB2002/000415 priority Critical patent/WO2003067952A2/fr
Priority to AU2002230036A priority patent/AU2002230036A1/en
Priority to EP02733001A priority patent/EP1485421A1/fr
Priority to PCT/IB2002/001708 priority patent/WO2003068843A1/fr
Priority to AU2002304373A priority patent/AU2002304373A1/en
Publication of WO2003067952A2 publication Critical patent/WO2003067952A2/fr
Anticipated expiration legal-status Critical
Publication of WO2003067952A3 publication Critical patent/WO2003067952A3/fr
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
    • C08J3/246—Intercrosslinking of at least two polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/005—Processes for mixing polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • C08J3/14—Powdering or granulating by precipitation from solutions
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • C08L33/02—Homopolymers or copolymers of acids; Metal or ammonium salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00

Definitions

  • the present invention relates to a solid, particulate composition formed by the inter-polymer complexation of a cationic polymeric glucosamine or its derivatives and an anionic, cross-linked, polyacrylic acid or its derivatives.
  • This complex is particularly useful in oral solid pharmaceutical compositions, including tablets and capsules.
  • inter-polymer complexes are ionically cross-linked hydrogels formed by the interaction of oppositely charged macromolecules.
  • the process of complexation is a useful technique to generate polymer systems, which 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, Van 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 the individual properties. Alternatively, the synergism may reflect in the separate manifestation in the complex of many of the properties of the interacting polymers.
  • US Patent No. 5,510,418 describes biocompatible, biologically inert conjugates comprising a chemically derivatized glycosaminoglycan chemically conjugated to a synthetic hydrophilic polymer, namely, polyethylene glycol.
  • the chemical conjugation may be by means of a variety of type of covalent linkages, including ether and ester linkages.
  • US Patent No. 3,962,158 describes hydrophilic polymer membranes useful as semi- permeable membranes or ultrafilter membranes, 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.
  • US Patent No. 4,501 ,835 describes a composition of matter, which is a complex of polyacrylic acid and chitosan, wherein the molecular weight of the polyacrylic acid is 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 and can be employed to form membranes and films.
  • US Patent No. 4,956,170 discloses a high alcohol content skin moisturizing / conditioning antimicrobial gel.
  • the gel comprises from about 60-75 weight percent of ethanol and from about 0.4- 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
  • a gelling agent preferably employed is an addition polymer of acrylic acid cross-linked with an unsaturated polyfunctional agent, such a polyalkyl ether of sucrose.
  • the present invention is directed to 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.
  • the cross-linked polyacrylic acid or its derivatives has a molecular weight of greater than or equal to 700,000.
  • the inter-polymer complex may optionally contain any pharmaceutical active and/or inactive ingredients.
  • the complexation process involves neutralization of an anionic, cross- linked polyacrylic acid or its derivatives using an aqueous solution of a cationic polymeric glucosamine or its derivatives.
  • the polyacrylate is reacted as a colloidal dispersion and the neutralization results in the precipitation of a complex as an insoluble gel mass.
  • the dispersion of the cross-linked acrylate polymer can either be in water or, more preferably, in a single or a mixture of organic solvent(s).
  • the solvent of choice is absolute ethanol.
  • the interaction can be in completely aqueous media or in hydro-organic system, and preferably, in hydro-alcoholic system.
  • the polymer complex obtained from hydro-alcoholic solvent system is easy to process, has high yields, and forms very highly swelling gels especially when mixed in aqueous media of pH greater than 3.
  • the gel obtained from aqueous media shows a lower water absorbing capacity and weaker texture properties.
  • Glucosamine which is formed in the body as glucosamine 6-phosphate, is 2-amino-2- deoxy-alpha-D-glucose. It is one of the two hexosamine sugars (6 carbon amino sugars) common in animal cells. Structurally, glucosamine is modified glucose with NH 3 -group replacing the OH-group found on carbon two (C-2). A glucosamine that is of particular relevance to this application is chitosan. Chitosan is poIy-[l- 4]-beta-D- glucosamine and is a partially deacetylated chitin.
  • glucosamines include carboxymethyl chitosan, hydroxypropyl chitosan and glycol chitosan.
  • Cross-linked polyacrylic acid or its derivatives include water- swellable, high molecular weight, cross-linked homopolymers and copolymers, which form hydrogels in aqueous media.
  • the crosslinker types and levels can be modified, with regard to amounts and characteristics of the hydrophobic co-monomers.
  • Commercial grades of cross- linked methacrylic acid are available from Noveon (formerly, BF Goodrich) as Carbopol®, Pemulen®, and Noveon resins.
  • 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 theoretically estimated to range from 700,000 to 3 or 4 billion.
  • 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 in non-aqueous gels are in the form of alkyl amides of di- and/or tri-basic carboxylic acids or anhydrides. Reacting the di- or tri-basic organic acid or anhydride, or the methyl ester form thereof, with the desired alkyl amine produces the gellant materials.
  • This gel- based technology makes use of an anhydrous or semi-hydrous liquid carrier.
  • Hydroalcoholic hand sanitizing gels have found increasing use due to their ability to instantly kill germs and bacteria, without the use of soap and water, together with pleasant after-feel on the hands owing to conditioning and moisturizing benefits.
  • Carbopol® polymers are preferred in these hydroalcoholic gels.
  • Hydroalcoholic gels with Carbopol® polymers also include neutralizing agents, which are effective at low levels of water in these systems.
  • the interaction of cross-linked polyacrylic acid with chitosan or its derivatives in hydro- organic system produces stronger gels than the same interaction in a completely aqueous media.
  • the organic solvent in hydro-organic system can be at least 20% by volume.
  • the level of organic solvent can be raised to about 95% by volume. With high proportions of the organic solvent, the complex formation and separation from the media as a gel precipitate is more complete. This is of particular benefit for production at large scale. However, due to commercial considerations, the levels of organic solvent is from about 70 to 90% by volume.
  • the complexation process involves neutralization of anionic functional groups in cross-linked polyacrylic acid or its derivatives with cationic functional groups of polyglucosamine or its derivatives.
  • the ratios of the interacting species can vary between 1 :20 and 20:1. Preferably, the ratio is at least 1 :10 and the most preferred ratio of the interacting species is 1 :1.
  • the neutralization is complete in 1 :1 ratio of the two interacting polymers and the resulting complex has water absorbing capacity (at pH greater than 3) of very high magnitude and results in a highly swollen gel. The rate of formation of the swollen gel is relatively fast.
  • the complex gel precipitate can be separated from the reacting carrier media by isolation techniques known in the art, which include but is not restricted to sedimentation, filtration, centrifugation, distillation, and evaporation.
  • the gel can be optionally rinsed with more solvent.
  • the gel is then dried by any suitable drying technique known in the art, which include but is not restricted to, oven drying, vacuum oven drying, fluid-bed drying, freeze drying, spray drying and microwave oven drying.
  • the dried material is desirably milled to obtain the complex as a dry, particulate solid material.
  • glucosamine is preferably used as an aqueous solution.
  • the glucosamine under consideration may optionally be dissolved in an acidified solution. Any acid or acid derivative which impart an acidic pH to the aqueous solutions may be used for the purpose of solubilisation.
  • It may be selected from a group consisting of sulphuric acid, hydrochloric acid, phosphoric acid, carboxylic acids, such as formic acid, acetic acid, malic acid, maleic acid, oxalic acid, succinic acid, tartaric acid, lactic acid, ascorbic acid, gluconic acid, amino acids and their derivatives/salts, glyceryl triacetate, polyvinyl acetate, and citric acid.
  • the other interacting polymer namely, cross- linked polyacrylic acid or its derivatives is preferably dispersed in an aqueous media as a colloidal hydro-gel or as a particulate dispersion in an organic solvent, preferably, an ester or a ketone.
  • Preferred solvents include, methanol, ethanol, isopropyl alcohol and acetone.
  • the solvent of choice is ethanol.
  • Interaction of the reacting polymers in two different phases and preferably in a hydro- organic solvent system produces the complex. If the solvent system is completely aqueous, the interaction results in a certain fraction that remains as a colloidal solution. Concentration of this phase by evaporation and subsequent drying in the oven gives relatively lower yield and also results in a film that is difficult to obtain as a solid particle. Experiments have shown this phase to contain around 50% of the yield. Use of hydro-alcoholic solvent system yields almost complete extraction of the complex from the solvent phase into the precipitated gel phase.
  • the complex forms a highly swelled gel in aqueous media of pH more than 3, entrapping 10 to 75 times its own mass of the solvent.
  • the solid material so obtained as mentioned above 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 firmness of the gel complex from hydro-alcoholic phase was much stronger than that obtained from the aqueous system.
  • Texture Expert Exceed (Stable Micro Systems, UK) is versatile equipment for measuring the texture of materials. It has applications in pharmaceutical, cosmetic, food and packaging industry . By suitable selection of tooling and probes, and by appropriate parameter settings, a wide range of materials can be evaluated for their texture properties. Measurement of texture properties in a gel includes its 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. The gels prepared, and not limiting to the examples cited herein, have been characterized and differentiated by means of the texture analyzer.
  • the texture analyzer Model- XT2i
  • the texture analyzer had an attached maximum load cell of 5 kg.
  • the pre-test, test and post-test speeds were 2 mm per second, 1 mm per second and 1 mm per second, respectively.
  • the travel distance in the gel was 10 mm.
  • Other settings include, trigger type -auto; trigger force -0.5 g; 'Measure force in compression'; 'Return to start' and PPS -200.
  • the gel obtained in this invention can serve a number of useful functions in pharmaceutical dosage forms, including, as a high bulk substance for oral administration, as a matrix in oral controlled release, in taste-masking, as a tablet disintegrant, among others.
  • Example-1 illustrate the preparation of an interpolymer complex within the scope of the present invention.
  • Example-1 illustrates the preparation of an interpolymer complex within the scope of the present invention.
  • Example-2 Cross-linked polyacrylic acid (Carbopol 971 P) (83.5 mg) was dispersed in pH 7.5 phosphate buffer (10 ml). The texture profile of the resulting gel has been shown in Fig. - 2.
  • Chitosan (0.2 g) was dissolved in an acidified solution of citric acid (0.1 g) in water (20 ml). Carbopol 971 P(0.02 g) was dispersed in absolute ethanol (60 ml). The solution of chitosan was added gradually into the ethanolic dispersion. The solvent was removed using vacuum distillation and the gel was freeze-dried.
  • Chitosan (0.2 g) was dissolved in an acidified solution of acetic acid (2.0 ml) in water (10 ml). Carbopol 971 P(0.2 g) was dispersed in absolute ethanol (60 ml). The solution of chitosan was added gradually into the ethanolic dispersion. The precipitated gel was isolated from the solvent phase and dried using hot-air oven. The dried material was milled and evaluated for degree of swelling and texture characteristics.
  • Fig. -3 shows the texture profile of the swollen complex (83.4 mg), in pH 7.5 buffer (10 ml).
  • Table -1 shows consolidated data for degree of swelling and texture properties, determined in pH 7.5 phosphate buffer media.
  • Chitosan (0.2 g) was dissolved in an acidified solution of acetic acid (2.0 ml) in water (10 ml). Carbopol 971 P(0.2 g) was dispersed as a colloidal solution in water (60 ml). The aqueous solution of chitosan was added gradually into the aqueous polyacrylate dispersion. The precipitated gel was isolated from the solvent phase and dried using hot- air oven. The dried material was milled and evaluated for degree of swelling and texture characteristics.
  • Fig. -4 shows the texture profile of the swollen complex (81.3 mg) in pH 7.5 buffer (10 ml).
  • Glycol chitosan (0.1 g) was dissolved in water (6 ml). Carbopol 971 P(0.1 g) was dispersed in absolute ethanol (100 ml). The solution of glycolchitosan was added gradually into the ethanolic dispersion. The precipitated gel was isolated from the solvent phase. The solvent phase was concentrated by evaporation and blend with the gel phase and dried using hot-air oven. The dried material was milled and evaluated for degree of swelling and texture characteristics.
  • Chitosan (0.05 g) was dissolved in an aqueous solution of hydrochloric acid, containing 10 ml water and acidified to a pH of 2.0 prior to dissolution.
  • Quinine sulphate (0.1 g) was dissolved in absolute ethanol (30 ml).
  • the solution of chitosan was added gradually into the ethanolic phase.
  • the precipitated gel was isolated from the solvent phase and dried using hot-air oven. The dried material was milled and evaluated for taste masking of quinine sulphate. The taste masking was found to be effective
  • Chitosan (0.2 g) was dissolved in an acidified solution of acetic acid (2.0 ml) in water (10 ml). Carbopol 971 P (0.2 g) was dispersed in acetone (60 ml). The solution of chitosan was added gradually into the non-aqueous dispersion phase. The precipitated gel was isolated from the solvent phase and dried using hot-air oven. The dried material was milled and evaluated for degree of swelling and texture characteristics.
  • Example -9 Chitosan (0.2 g) was dissolved in an acidified solution of acetic acid (0.2 ml) in water (19.8 ml). Croscarmellose sodium NF (Ac-Di-Sol, FMC) (0.1 g) and Carbopol 971 P(0.3 g) were dispersed in absolute ethanol (60 ml). The solution of chitosan was added gradually into the ethanolic dispersion. The precipitated gel was isolated from the solvent phase and dried using hot-air oven. The dried material was milled and evaluated for degree of swelling and texture characteristics.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une composition solide particulaire formée par la complexation inter-polymère d'une glucosamine polymérique cationique ou de ses dérivés et d'un acide polyacrylique réticulé anionique ou de ses dérivés. Ce complexe est utilisé, en particulier, dans des compositions pharmaceutiques solides administrées par voie orale, y compris les comprimés et les capsules.
PCT/IB2002/000415 2002-02-12 2002-02-12 Complexe de glucosamine-polyacrylate inter-polymere et applications Ceased WO2003067952A2 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
PCT/IB2002/000415 WO2003067952A2 (fr) 2002-02-12 2002-02-12 Complexe de glucosamine-polyacrylate inter-polymere et applications
AU2002230036A AU2002230036A1 (en) 2002-02-12 2002-02-12 Glucosamine-polyacrylate inter-polymer complex and applications thereof
EP02733001A EP1485421A1 (fr) 2002-02-12 2002-05-20 Complexe inter-polymere de glucosamine-polyacrylate et applications dudit complexe
PCT/IB2002/001708 WO2003068843A1 (fr) 2002-02-12 2002-05-20 Complexe inter-polymere de glucosamine-polyacrylate et applications dudit complexe
AU2002304373A AU2002304373A1 (en) 2002-02-12 2002-05-20 Glucosamine-polyacrylate inter-polymer complex and applications thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2002/000415 WO2003067952A2 (fr) 2002-02-12 2002-02-12 Complexe de glucosamine-polyacrylate inter-polymere et applications

Publications (2)

Publication Number Publication Date
WO2003067952A2 true WO2003067952A2 (fr) 2003-08-21
WO2003067952A3 WO2003067952A3 (fr) 2007-11-29

Family

ID=27676599

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/IB2002/000415 Ceased WO2003067952A2 (fr) 2002-02-12 2002-02-12 Complexe de glucosamine-polyacrylate inter-polymere et applications
PCT/IB2002/001708 Ceased WO2003068843A1 (fr) 2002-02-12 2002-05-20 Complexe inter-polymere de glucosamine-polyacrylate et applications dudit complexe

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/IB2002/001708 Ceased WO2003068843A1 (fr) 2002-02-12 2002-05-20 Complexe inter-polymere de glucosamine-polyacrylate et applications dudit complexe

Country Status (3)

Country Link
EP (1) EP1485421A1 (fr)
AU (2) AU2002230036A1 (fr)
WO (2) WO2003067952A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005087202A1 (fr) * 2004-02-10 2005-09-22 Ranbaxy Laboratories Limited Complexe interpolymere de glucosamine polyacrylate et procedes de production correspondants
EP1507813A4 (fr) * 2002-05-20 2005-11-23 Ranbaxy Lab Ltd Liaison a la graisse au moyen d'un complexe interpolymere de glucosamine et d'acide polyacrylique
CN109350606A (zh) * 2018-09-26 2019-02-19 青岛大学 一种聚电解质中空胶囊的制备方法及得到的中空胶囊

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005030173A1 (fr) * 2003-09-25 2005-04-07 Ranbaxy Laboratories Limited Liberation de medicaments specifiques au colon au moyen de complexation interpolymeres
GB0625813D0 (en) * 2006-12-22 2007-02-07 Advanced Biopolymers As Process
EP3199147B1 (fr) * 2009-04-22 2020-05-27 MedSkin Solutions Dr. Suwelack AG Composition d'agents actifs lyophilisés
JP5724108B2 (ja) 2009-04-22 2015-05-27 メドスキン ソリューションズ ドクター ズベラック アーゲーＭｅｄＳｋｉｎ Ｓｏｌｕｔｉｏｎｓ Ｄｒ．Ｓｕｗｅｌａｃｋ ＡＧ 凍結乾燥組成物
US9309435B2 (en) 2010-03-29 2016-04-12 The Clorox Company Precursor polyelectrolyte complexes compositions comprising oxidants
US20110236582A1 (en) 2010-03-29 2011-09-29 Scheuing David R Polyelectrolyte Complexes
US9474269B2 (en) 2010-03-29 2016-10-25 The Clorox Company Aqueous compositions comprising associative polyelectrolyte complexes (PEC)
US9162098B2 (en) * 2012-01-13 2015-10-20 Icl Performance Products Lp Liquid gel concentrate compositions and methods of use
US8975220B1 (en) 2014-08-11 2015-03-10 The Clorox Company Hypohalite compositions comprising a cationic polymer
CN106310229A (zh) * 2015-06-30 2017-01-11 深圳翰宇药业股份有限公司 一种马昔瑞林薄膜衣片及其制备方法
KR101882820B1 (ko) 2015-12-30 2018-07-30 주식회사 삼양바이오팜 점막부착성 약학 조성물 및 그의 제조방법
CN110477032A (zh) * 2019-07-15 2019-11-22 华南理工大学 一种基于紫茎泽兰提取物的羟丙基壳聚糖/羧甲基壳聚糖载药粒子及其制备方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5241797B2 (fr) * 1974-04-05 1977-10-20
US4447562A (en) * 1981-07-15 1984-05-08 Ivani Edward J Amino-polysaccharides and copolymers thereof for contact lenses and ophthalmic compositions
US4501835A (en) * 1982-03-08 1985-02-26 Polaroid Corporation Polyacrylic acid/chitosan polyelectrolyte complex
US4767463A (en) * 1987-04-15 1988-08-30 Union Carbide Corporation Glycosaminoglycan and cationic polymer combinations
US5510418A (en) * 1988-11-21 1996-04-23 Collagen Corporation Glycosaminoglycan-synthetic polymer conjugates
US6060410A (en) * 1998-04-22 2000-05-09 Gillberg-Laforce; Gunilla Elsa Coating of a hydrophobic polymer substrate with a nonstoichiometric polyelectrolyte complex

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1507813A4 (fr) * 2002-05-20 2005-11-23 Ranbaxy Lab Ltd Liaison a la graisse au moyen d'un complexe interpolymere de glucosamine et d'acide polyacrylique
WO2005087202A1 (fr) * 2004-02-10 2005-09-22 Ranbaxy Laboratories Limited Complexe interpolymere de glucosamine polyacrylate et procedes de production correspondants
CN109350606A (zh) * 2018-09-26 2019-02-19 青岛大学 一种聚电解质中空胶囊的制备方法及得到的中空胶囊
CN109350606B (zh) * 2018-09-26 2021-08-13 青岛大学 一种聚电解质中空胶囊的制备方法及得到的中空胶囊

Also Published As

Publication number Publication date
EP1485421A1 (fr) 2004-12-15
WO2003068843A1 (fr) 2003-08-21
AU2002304373A1 (en) 2003-09-04
AU2002230036A1 (en) 2003-09-04
WO2003067952A3 (fr) 2007-11-29
AU2002230036A8 (en) 2003-09-04

Similar Documents

Publication Publication Date Title
WO2003067952A2 (fr) Complexe de glucosamine-polyacrylate inter-polymere et applications
CA1295611C (fr) Complexe d'association a base de pullulane et de polyethyleneglycol,leur preparation et leurs utilisations
DE68912882T2 (de) Wirkstoff-Harzkomplexe mit verzögerter Freigabe.
US6165509A (en) Pegylated drug complexed with bioadhesive polymer suitable for drug delivery and methods relating thereto
EP0585688B1 (fr) Dispersions aqueuses de zéine et revêtements formés à partir de ces dispersions à libération contrÔlée
US6596791B2 (en) Polymer complexes of glucuronoglucanes
EP0271551B1 (fr) Decristallisation acide de chitosan fortement cristallise ou de chitine partiellement deacetylee
US3629392A (en) Entrapment compositions and processes
JPH06501029A (ja) 生体活性組成物
EP2964204B1 (fr) Nouveaux éthers de cellulose estérifiés de très faible viscosité
IE70747B1 (en) A pharmacological composition containing polyelectrolyte complexes in microparticulate form and at least one active substance
WO1991007949A1 (fr) Compositions a liberation retardee
Pal et al. Synthesis of pH-sensitive crosslinked guar gum-g-poly (acrylic acid-co-acrylonitrile) for the delivery of thymoquinone against inflammation
JPH09286921A (ja) 疎水性基で修飾された生物学的接着性を有する高分子電解質およびそれに関連する方法
do Nascimento et al. Supramolecular aggregates of cyclodextrins with co-solvent modulate drug dispersion and release behavior of poorly soluble corticosteroid from chitosan membranes
US20070077305A1 (en) Biocompatible polymeric matrix and preparation thereof
TW201124142A (en) Hypersulfated disaccharide formulations
WO2022090296A1 (fr) Composition pharmaceutique et procédé d'amélioration de la solubilité d'ingrédients pharmaceutiques actifs faiblement solubles
WO2005087202A1 (fr) Complexe interpolymere de glucosamine polyacrylate et procedes de production correspondants
US20020058704A1 (en) Multicomponent compositions containing chitosan and methods of preparing same
USRE28316E (en) Entrapment compositions and processes
JPH0425930B2 (fr)
EP1003555A1 (fr) Liberation controlee de compositions ophtalmiques
MXPA04000332A (es) Preparaciones farmaceuticas que contienen resinas cambiadoras de iones cargadas de sustancia activa.
Pathan et al. Enhancement of in-vitro dissolution efficiency of cefixime trihydrate using natural polymer by solid dispersion technique

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP