Multiphase soft gelatin dosage form

• US 6,024,980 A
• Filed: 06/28/1996
• Issued: 02/15/2000
• Est. Priority Date: 06/28/1996
• Status: Expired due to Term

• Current Assignee: Johnson & Johnson Consumer Inc. (Johnson & Johnson)
• Original Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Inventors: Hoy, Michael R.
• Primary Examiner(s): Spear, James M.
• Application Number:
  US08/671,979
• Time in Patent Office: 1,327 Days
• Field of Search: 424/451, 424/452, 424/455, 424/456, 424/457, 424/454
• US Class Current: 424/456
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/12 Antidiarrhoeals

Abstract

The present invention relates to a dosage form containing a common enclosure of polymeric material. The enclosure contains multiple phases of semi-solid fill materials containing active ingredients.

Claims

1. A pharmaceutical dosage form, comprising:

a gelatin capsule shell;

a first phase comprising a first semi-solid containing a polyalkylene glycol having an average molecular weight of about 600 or less and a cellulose ether in an amount effective to thicken the polyalkylene glycol, a therapeutically effective amount of a first pharmaceutical dissolved or suspended in said first semi-solid and said first semi-solid having a turbidity less than about 1300 NTU;

a second phase comprising a second semi-solid fill containing a polyalkylene glycol having an average molecular weight of about 400 to about 20,000 and a therapeutically effective amount of a second pharmaceutical disposed in said semi-solid; and

said first and second phases each disposed in discrete regions of said shell and in contact with each other at at least one interface.

2. The dosage form of claim 1 wherein in said first semi-solid the polyalkylene glycol is polyethylene glycol.

3. The dosage form of claim 1 wherein the turbidity of said first semi-solid is less than about 200 NTU.

4. The dosage form of claim 1 wherein said first semi-solid further comprises propylene glycol.

5. The dosage form of claim 1 wherein said first semi-solid comprises by weight:

about 35 to about 99 percent of the polyalkylene glycol;

0 to about 10 percent propylene glycol;

0 to about 10 percent of water; and

about 0.1 to about 10 percent of the cellulose ether.

6. The dosage form of claim 5 wherein said first semi-solid comprises polyethylene glycol having an average molecular weight of about 200 to about 600.

7. The dosage form of claim 1 wherein in said first semi-solid the cellulose ether is hydroxypropyl cellulose.

8. The dosage form of claim 7 wherein in said first semi-solid the cellulose ether is hydroxypropyl cellulose having a molecular weight of about 80,000 to about 1,150,000.

9. The dosage form of claim 1 wherein said first pharmaceutical is selected from the group consisting of acetaminophen, famotidine, chlorpheniramine, pseudoephedrine, dextromethorphan, diphenhydramine, brompheniramine, clemastine, phenylpropanolamine, terfenadine, astemizole, loratadine, loperamide, loperamide-N-oxide, ranitidine, cimetidine, tramadol, cisapride, acetylsalicylic acid, doxylamine succinate, pharmaceutically acceptable salts thereof and mixtures thereof.

10. The dosage form of claim 1 wherein said first semi-solid comprises polyethylene glycol having an average molecular weight of about 300 to about 400 and hydroxypropyl cellulose.

11. The composition of claim 10 wherein the first semi-solid comprises by weight:

about 85 to about 99 percent of polyethylene glycol having an average molecular weight of about 300 to about 400;

0 to about 8 percent propylene glycol; and

about 0.25 to about 3.5 percent of a hydroxypropyl cellulose having an average molecular weight of about 300,000 to about 1,200,000.

12. The dosage form of claim 11 wherein said first semi-solid has a viscosity of at least 30,000 centipoise at 25°

C.

13. The composition of claim 12 wherein said first semi-solid comprises by weight:

about 1 to about 3 percent loperamide HCl;

about 92 to about 99 percent polyethylene glycol having an average molecular weight of about 400;

0 to about 8 percent water;

0 to about 8 percent propylene glycol; and

about 0.5 to about 3 percent hydroxypropyl cellulose.

14. The dosage form of claim 1 wherein in said second semi-solid the polyalkylene glycol is polyethylene glycol.

15. The dosage form of claim 1 wherein said second semi-solid has a viscosity of about 10,000 to about 2,500,000 centipoise at 25°

C.

16. The dosage form of claim 1 wherein said second semi-solid further comprises auxiliary semi-solid forming agents selected from the group consisting of propylene glycol, polyglyceryl-6-distearate, glycerol oleate and hydroypropyl cellulose.

17. The dosage form of claim 1 wherein said second semi-solid, comprises by weight:

about 30 to about 70 percent of polyethylene glycol and

about 30 to about 70 percent of antiflatulent.

18. The dosage form of claim 1 wherein said second semi-solid comprises by weight about 0.25 to about 5 percent of a polyethylene glycol having an average molecular weight of about 600 or less and about 45 to about 50 percent of a polyethylene glycol having an average molecular weight of greater than about 600 to about 10,000.

19. The dosage form of claim 1 wherein said second semi-solid comprises an antiflatulent and has a defoam time of less than about 15 seconds.

20. The dosage form of claim 1 wherein said second semi-solid has a syringeability of less than about 0.5 gram.

21. The dosage form of claim 1 wherein in said second semi-solid the pharmaceutical is selected from the group consisting of simethicone and dimethicone.

22. The dosage form of claim 1, wherein said second semi-solid comprises by weight:

about 40 to about 60 percent of polyethylene glycol having an average molecular weight of about 400 to about 3350 and

about 40 to about 60 percent of simethicone.

23. The dosage form of claim 22 wherein said second semi-solid has a viscosity of about 400,000 to about 2,000,000 centipoise at 25°

C.

24. The dosage form of claim 1 wherein said second semi-solid comprises by weight:

about 40 to about 60 percent simethicone;

about 1 to about 3 percent polyethylene glycol having an average molecular weight of about 300 to about 400; and

about 40 to about 60 percent polyethylene glycol having an average molecular weight of about 1450 to about 4600.

25. The dosage form of claim 24 wherein said second semi-solid has a viscosity of about 900,000 to about 1,000,000 centipoise at 25°

C., a defoam time of less than about 8 seconds and a syringeability of less than about 0.5 gram.