Pharmaceutical capsule compositions and structures for gastric sensitive materials

• US 4,601,896 A
• Filed: 03/21/1984
• Issued: 07/22/1986
• Est. Priority Date: 03/21/1984
• Status: Expired due to Fees

• Current Assignee: NUGENT, BONNIE L. (1/2), NUGENT, D. EUGENE (1/2)
• Original Assignee: Mark Nugent
• Inventors: Nugent, Mark
• Primary Examiner(s): Griffin, Ronald W.
• Application Number:
  US06/591,972
• Time in Patent Office: 853 Days
• Field of Search: 424/21, 424/37, 424/36, 106/124, 106/125, 106/128, 106/131, 206/530, 260/DIG. 43
• US Class Current: 424/453
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: Y10S 220/34 Anti-tamper pharmaceutical capsules, e.g. tamper indicating or resistant
• CPC Class Codes: Y10S 260/43 Promoting degradability of polymers

Abstract

This invention provides oral dosage forms of therapeutic agents such as digestive enzymes which are subject to degradation and loss of activity at gastric pH. and compositions and methods for preparing same. Capsules of their components are formulated from a composition comprising a plastic homogeneous mass of gastric fluid impervious material such as cellulosic derivatives or collagenous material; from 10-65% by weight of a diluent selected from the group consisting of water, a lipid having a melting point above mammalian body temperature and a water miscible solvent; 4-60% by weight of procollagen; and 30-86% by weight of collagen or elastin. The composition is formed into finished capsules of relatively homogeneous composition comprising 10-50% by weight of procollagen and 40-96% by weight of a material selected from the group consisting of collagen and elastin, and having less than 4% by weight of fat and water-soluble protein. Prior art pH dependent enteric coat materials such as cellulose acetate phthalate may be incorporated at a level of 1.0-40%. At time of oral administration, an activator capable of dissolving the capsule wall is allowed to contact the interior surface of the capsule. In the case of cellulosic composition outer walls, cellulose or a non-enzymatic alkaline buffer is applied, and a proteolytic enzyme is employed to dissolve collagenous materials.

Claims

1. A pharmaceutical capsule blank adapted for oral administration of gastric-sensitive therapeutic agents, said capsule blank fabricated from a composition comprising a substantially homogeneous and gastric-fluid impervious composition comprising from about 10 to 50 percent by weight of procollagen, from about 40 to 96 percent by weight of at least one material selected from the group consisting of collagen and elastin, and less than 4 weight percent fat and albumin derived from said collagen or elastin source.

2. The capsule blank of claim 1, said blank including a chamber for containing a therapeutically effective amount of a gastric- sensitive medicament and a proteolytic enzyme capable of lysing said procollagen.

3. The capsule blank of claim 1, said blank including a first interior chamber for containing a therapeutically effective amount of a gastric-sensitive medicament and a second chamber adapted to releasably contain a material capable of dissolving the walls of said capsule blank when said material is released from said second chamber.

4. The capsule blank of claim 1 wherein said procollagen is present in an amount of from 10 to 20 weight percent.

5. A pharmaceutical capsule adapted for oral administration of a gastric-sensitive therapeutic agent, said capsule comprising an outer housing, said housing containing a first chamber, said first chamber filled with a therapeutically effective amount of said therapeutic agent;

a second chamber, said second chamber containing an activator material capable of dissolving said capsule;

said second chamber being contiguous to said housing, said housing comprising 10 to 50 percent by weight of procollagen, 40-96 weight percent of a material selected from the group consisting of collagen and elastin, and containing less than 4 weight percent fat or protein derived from said collagen or elastin.

6. The capsule of claim 5 wherein said housing is deformable whereby external deforming pressure may be applied to said capsule surface to cause rupturing of said second chamber, thereby allowing escape of said activator from said second chamber and contact of said activator with said housing.

7. The capsule of claim 5 wherein said activator material is a proteolytic enzyme capable of lysing said procollagen.

8. The capsule of claim 5 wherein said housing additionally comprises from 15 to 35 weight percent of cellulose acetate phthalate.

9. A composition of matter suitable for fabrication into housings for oral unit dosage forms of gastric-sensitive medicaments comprising:

a plastic homogeneous mass of from 40 to 96 weight percent of collagen or elastin having substantially all naturally occurring lipids and water-soluble protein removed therefrom;

from about 10-50 weight percent of procollagen; and

sufficient diluent to render said mass pliable for fabrication.

10. The composition of claim 9 additionally comprising from 1.0% to 40% by weight of pH dependant non-collagenous enteric pharmaceutically acceptable coat composition, provided that the procollagen level is 10% to 50% by weight of the total composition.

11. The composition of claim 9 additionally comprising from 15% to 35% by weight of cellulose acetate phthalate, provided the procollagen content is 10% to 50% of the total weight.

12. A pharmaceutical oral unit dosage form for administering gastric-sensitive materials to a mammalian host comprising:

a capsule having a resilient outer wall which is impervious to gastric fluids, said outer wall defining a first chamber adapted to house a therapeutically effective amount of a gastric sensitive medicament;

said unit dosage form further including pharmaceutically acceptable activator fluid contained within said capsule, said fluid causing digestion of said capsule wall on a timed basis so as to release said gastric-sensitive medicament into the lower intestinal tract.

13. The unit dosage form of claim 12 wherein said chamber is filled with said gastric sensitive medicament and said pharmaceutically acceptable activator fluid immediately prior to administration of said capsule.

14. The unit dosage form of claim 12 wherein said capsule further comprises a second chamber, said second chamber housing said pharmaceutically acceptable activator fluid which is released into said first chamber when said second chamber is ruptured.

15. The unit dosage form of claim 14 wherein said second chamber is defined by a brittle wall capable of rupturing when external deforming pressure is applied to said resilient capsule wall.

16. A pharmaceutically acceptable oral unit dosage composition which is substantially homogeneous and gastric-fluid impervious comprising from about 10% to 50% procollagen by weight and at least 40% by weight of at least one material selected from the group consisting of collagen and elastin, substantially free of native fat and water-soluble protein.

17. A method of administering a therapeutically effective amount of a gastric-sensitive medicament to a patient in need of said treatment comprising orally administering said medicament to said patient in a housing which is impervious to gastric fluid, said unit dosage form including an activator which dissolves said housing at a pre-determined time so as to predictably release said medicament into the intestinal tract of said patient.

18. The method of claim 17 wherein said medicament and said pharmaceutically acceptable activator are introduced into said housing immediately before administration.

19. The method of claim 17 wherein said medicament and said pharmaceutically acceptable activator are present in a finished unit dosage form, said unit dosage form comprising a housing which includes a first chamber and a second chamber, said first chamber containing said medicament and said second chamber containing said activator, said activator being released when pressure is applied to said unit dosage form so as to rupture a wall of said second chamber thereby releasing activator whereby said activator contacts and dissolves said housing, releasing medicament into said patient'"'"'s intestinal tract.