Microcapsules containing medicament-polymer salt having a water-insoluble polymer sheath, their production and their use

• US 4,205,060 A
• Filed: 12/20/1978
• Issued: 05/27/1980
• Est. Priority Date: 12/20/1978
• Status: Expired due to Term

• Current Assignee: Astra AB (Astrazeneca PLC)
• Original Assignee: Pennwalt Corporation (Arkema)
• Inventors: Monsimer, Harold G., Bohm, Howard A.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US05/971,243
• Time in Patent Office: 524 Days
• Field of Search: 252/316, 424/14-38, 424/78-83
• US Class Current: 424/495
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

Microcapsules comprising a core containing a water-soluble salt of a medicament and a polymer, e.g., the salt of a medicament containing an amine-group and a carboxyl group containing polymer, and a sheath of a water-insoluble film forming polymer, e.g., ethyl cellulose, the method of their production and their administration are disclosed. The microcapsules can be formed by dispersing an aqueous solution of the medicament-polymer salt in a water-immiscible solvent solution of a water-insoluble film forming polymer, adding another water-immiscible solvent which is a non-solvent for the water-insoluble polymer, and collected the microcapsules. The microcapsules are administered orally to animals and exhibit substantially slower release rates and more uniform release rates in stomach acids than the corresponding unencapsulated salts or encapsulated non-polymeric salts.

Claims

1. Microcapsules comprising a core containing a water-soluble salt formed from a medicament and a water-soluble polymer, and a sheath of a water-insoluble film forming polymer wherein said salt is selected from one member of the group consisting of (1) a salt of a medicament which contains at least one basic group and a water-soluble polymer which contains at least one acid group and (2) a salt of a medicament which contains at least one acid group and a water-soluble polymer which contains at least one basic group;

said microcapsules having an average particle size from about 0.5 to 50 microns.

2. Microcapsules of claim 1 in which said sheath of a water-insoluble film forming polymer comprises ethyl cellulose, cellulose acetate, cellulose acetate butyrate, cellulose acetate phthalate, polyvinyl butyral, polyvinyl acetate, polymethyl methacrylate or polystyrene.

3. Microcapsules of claim 1 wherein said water soluble polymer is polyacrylic acid, water soluble copolymer of acrylic acid and copolymerizable monomer, hydrolyzed copolymer of maleic anhydride and vinyl methyl ether, polymers or copolymers of maleic acid or fumaric acid, alginic acid, carboxymethylcellulose or polyvinylsulfonic acid.

4. Microcapsules of claim 1 having a release of less than 100% after three hours in 0.1 N hydrochloric acid.

5. Microcapsules of claim 1 in which said medicament is dextromethorphan, ephedrine, pseudoephedrine, p-aminosalicylic acid, acetaminophen and chlorpheniramine.