Sustained-release pharmaceutical tablet and process for preparation thereof

• US 4,415,547 A
• Filed: 06/14/1982
• Issued: 11/15/1983
• Est. Priority Date: 06/14/1982
• Status: Expired due to Fees

• Current Assignee: Sanofi S.A. (Sanofi )
• Original Assignee: Sterling Drug, Inc. (GSK plc)
• Inventors: John, Phillip M., Yu, Andrew B. C.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US06/388,435
• Time in Patent Office: 519 Days
• Field of Search: 424/19-22, 424/32, 424/33, 424/35
• US Class Current: 424/469
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5078 with drug-free core

Abstract

A sustained-release pharmaceutical tablet consisting essentially of drug pellets encapsulated with a water-soluble film-forming substance and a water-insoluble film-forming substance and blended and compressed into tablet form with a compressible tableting mixture and a process for preparation thereof are disclosed.

Claims

1. A sustained-release pharmaceutical tablet consisting essentially of

(A) from about 35% to about 85% by weight of a plurality of encapsulated pellets each consisting essentially of

(a) from about 30% to about 98% by weight of a sugar-starch bead which is coated with

(b) from about 1% to about 70% by weight of a first coat consisting of from about 75% to about 99% by weight of theophylline an orally administrable drug and from about 1% to about 25% by weight of a water-soluble drug-binding substance selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose and hydroxypropyl methycellulose and

(c) from about 1% to about 15% by weight of a second coat consisting essentially of from about 1% to about 10% by weight of a water-soluble film-forming substance selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose and hydroxypropyl methylcellulose, from about 1% to about 60% by weight of a water-insoluble film-forming substance consisting of ethylcellulose and from about 30% to about 98% by weight of a dusting powder selected from the group consisting of talc, silicon dioxide and titanium dioxide, which encapsulated pellets are blended and compressed into tablet form with

(B) from about 15% to about 65% by weight of a compressible tableting mixture consisting essentially of from about 20% to about 40% by weight of a diluent selected from the group consisting of the monosaccharides and the disaccharides, from about 30% to about 50% by weight of a diluent-binder consisting of microcrystalline cellulose, from about 10% to about 30% by weight of a binder consisting of ethyl cellulose, and from about 5% to about 20% by weight of a hydrophobic lubricant selected from the group consisting of hydrogenated vegetable oil, stearic acid, magnesium stearate and calcium sterate.

2. A sustained-release pharmaceutical tablet according to claim 1 wherein the water-soluble drug-binding substance is polyvinylpyrrolidone, the water-soluble film-forming substance is polyvinylpyrrolidone, the water-insoluble film-forming substance is ethylcellulose, the dusting powder is talc, the diluent is lactose, and the hydrophobic lubricant is hydrogenated vegetable oil.

3. A sustained-release pharmaceutical tablet according to claim 2 wherein the second coat contains about 2% by weight of polyvinylpyrrolidone and about 46% by weight of ethylcellulose, the encapsulated pellets contain about 56% by weight of theophylline, and the tablet contains about 77% by weight of encapsulated pellets.

4. A sustained-release pharmaceutical tablet according to claim 2 wherein the second coat contains about 2% by weight of polyvinylpyrrolidone and about 2% by weight of ethylcellulose, the encapsulated pellets contain about 56.8% by weight of theophylline, and the tablet contains about 76% by weight of encapsulated pellets.

5. The process of preparing a sustained-release pharmaceutical tablet which comprises blending and compressing into tablet form a mixture consisting essentially of

(A) from about 35% to about 85% by weight of a plurality of encapsulated pellets each consisting essentially of

(a) from about 30% to about 98% by weight of a sugar-starch bead which is coated with

(b) from about 1% to about 70% by weight of a first coat consisting of from about 75% to about 99% by weight of theophylline an orally administrable drug and from about 1% to about 25% by weight of a water-soluble drug-binding substance selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose and hydroxypropyl methylcelluose and

(c) from about 1% to about 15% by weight of a second coat consisting essentially of from about 1% to about 10% by weight of a water-soluble film-forming substance selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose and hydroxypropyl methylcellulose, from about 1% to about 60% by weight of a water-insoluble film-forming substance consisting of ethylcellulose and from about 30% to about 98% by weight of a dusting powder selected from the group consisting of talc, silicon dioxide and titanium dioxide;

wherein the first coat is formed by simultaneously applying the drug in powder form by dusting and the water-soluble drug-binding substance as a solution in a non-aqueous solvent by spraying and the second coat is formed by simultaneously applying the water-soluble film-forming substance and the water-insoluble film-forming substance as a solution in a nonaqueous solvent by spraying and the dusting powder by dusting; and

(B) from about 15% to about 65% by weight of a compressible tableting mixture consisting essentially of from about 20% to about 40% by weight of a diluent selected from the group consisting of the monosaccharides and the disaccharides, from about 30% to about 50% by weight of a diluent-binder consisting of microcrystalline cellulose, from about 10% to about 30% by weight of a binder consisting of ethylcellulose, and from about 5% to about 20% by weight of a hydrophobic lubricant selected from the group consisting of hydrogenated vegetable oil, stearic acid, magnesium stearate and calcium stearate.

6. The process according to claim 5 wherein the water-soluble drug-binding substance is polyvinylpyrrolidone, the water-soluble film-forming substance is polyvinylpyrrolidone, the water-insoluble film-forming substance is ethylcellulose, the dusting powder is talc, the diluent is lactose, and the hydrophobic lubricant is hydrogenated vegetable oil.

7. The process according to claim 6 wherein the second coat contains about 2% by weight of polyvinylpyrolidone and about 46% by weight of ethylcellulose, the encapsulated pellets contain about 56% by weight of theophylline, and the tablet contains about 77% by weight of encapsulated pellets.

8. The process according to claim 6 wherein the second coat contains about 2% by weight of polyvinylpyrrolidone and about 2% by weight of ethylcellulose, the encapsulated pellets contain about 56.8% by weight of theophylline, and the tablet contains about 76% by weight of encapsulated pellets.