Sustained-release preparation applicable to mucous membrane in oral cavity

• US 4,740,365 A
• Filed: 04/05/1985
• Issued: 04/26/1988
• Est. Priority Date: 04/09/1984
• Status: Expired due to Term

• Current Assignee: Toyoda Gosei Company Limited (Toyota Motor Corporation)
• Original Assignee: Toyoda Gosei Company Limited (Toyota Motor Corporation)
• Inventors: Sogabe, Masae, Yasuda, Yoshihisa, Kakumoto, Munetaka, Tsujimoto, Junko, Yukimatsu, Keiji
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US06/720,461
• Time in Patent Office: 1,117 Days
• Field of Search: 424/19-22, 424/78, 424/80, 424/435
• US Class Current: 424/435
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

A sustained-release preparation applicable to mucous membrane in oral cavity which comprises an active ingredient and a mixture of a polymer component (A) comprising one or more polymers selected from polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, alginic acid or a salt thereof, and an alternating copolymer of maleic anhydride and methyl vinyl ether and a polymer component (B) comprising one or more polymers selected from polyacrylic acid and a salt thereof, said polymer component (A) and polymer component (B) being contained in a ratio of 95:5 to 5:95 by weight, and optionally in admixture with conventional carrier and additives. Said preparation may be formed in the form of a two-layer preparation with a layer comprising an active ingredient and one or more polymers selected from polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, alginic acid or a salt thereof, and an alternating copolymer of maleic anhydride and methyl vinyl ether and optionally in admixture with conventional carrier and additives. The preparation can easily be adhered to mucous membrane within oral cavity and maintained for a long period of time and the medicament (e.g. nifedipine) contained therein is released into saliva continuously to exhibit the activity effectively.

Claims

1. A sustained-release preparation applicable to mucous membrane in oral cavity, which comprises an active ingredient and a mixture of a polymer component (A) comprising one or more polymers selected from polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, alginic acid or a pharmaceutically acceptable salt thereof, and an alternating copolymer of maleic anhydride and methyl vinyl ether and a polymer component (B) comprising one or more polymers selected from polyacrylic acid and a pharmaceutically acceptable salt thereof, said polymer component (A) and polymer component (B) being contained in a ratio of 95:

5 to 5;

95 by weight.

2. The sustained-release preparation according to claim 1, wherein the active ingredient is nifedipine in the form of a solid solution in polyvinylpyrrolidone of the polymer component (A).

3. The sustained-release preparation according to claim 2, wherein the polyvinylpyrrolidone used for the solid solution has a molecular weight of 1×

10⁴ to 1×

10⁵.

7. The sustained-release preparation of claim 1 wherein said active ingredient and said polymer components (A) and (B) are in admixture with at least one additive ingredient selected from the group consisting of excipients, lubricants, binding agents, and flavors and seasonings, said additive ingredients being incorporated in an amount of not more than 40% by weight based on the total weight of the preparation.

8. The sustained-release preparation of claim 7 wherein said at least one additive ingredient is selected from the group consisting of talc, stearic acid, salts of stearic acid, waxes, starches, dextrin, tragacanth, gelatin, hydroxypropyl cellulose, crystalline cellulose, lactose, mannitol, sorbitol, anhydrous calcium phosphate, citric acid, fumaric acid, tartaric acid, menthol and citrus fruit flavors.

4. A sustained-release preparation applicable to mucous membrane in oral cavity, which comprises

a layer (I) comprising an active ingredient and one or more polymers selected from polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, alginic acid or a pharmaceutically acceptable salt thereof, and an alternating copolymer of maleic anhydride and methyl vinyl ether and optionally in admixture with conventional carrier and additives, said polymer being contained in an amount of not less than 20% by weight based on the whole weight of the layer (I), and

a layer (II) comprising an active ingredient and a mixture of a polymer component (A) comprising one or more polymers selected from polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, alginic acid or a pharmaceutically acceptable salt thereof, and an alternating copolymer of maleic anhydride and methyl vinyl ether and a polymer component (B) comprising one or more polymers selected from polyacrylic acid and a pharmaceutically acceptable salt thereof, said polymer component (A) and polymer component (B) being contained in a ratio of 95:

5 to 5;

95 by weight.

5. The sustained-release preparation according to claim 4, wherein the layer (I) comprises a solid solution of nifedipine in polyvinylpyrrolidone and a pharmaceutically acceptable carrier, said polyvinylpyrrolidone being contained in an amount of 20 to 80% by weight based on the whole weight of the layer (I), and the layer (II) comprises a solid solution of nifedipine in polyvinylpyrrolidone and polyacrylic acid and/or a pharmaceutically acceptable salt thereof, said solid solution and polyacrylic acid and/or a salt thereof being contained in a ratio of 95:

5 to 5;

95 by weight.

6. The sustained-release preparation according to claim 5, wherein the polyvinylpyrrolidone used for the layer (I) has a molecular weight of 1×

10⁴ to 1×

10⁵, and the polyvinylpyrrolidone used for the layer (II) has a molecular weight of 1×

10⁵ to 4×

10⁵.