Delivery of drugs to the lower GI tract

• US 5,811,388 A
• Filed: 02/16/1996
• Issued: 09/22/1998
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Amarin Development AB (Abbvie Incorporated)
• Original Assignee: Cibus Pharmaceutical, Inc.
• Inventors: Wong, David, Friend, David R.
• Primary Examiner(s): Russel, Jeffrey E.
• Application Number:
  US08/602,611
• Time in Patent Office: 949 Days
• Field of Search: 514/2, 514/3, 514/12, 514/21, 514/177, 514/178, 514/179, 514/180, 514/181, 514/182, 514/960, 514/961, 514/777, 514/780, 514/782, 424/85.1, 424/452, 424/461, 424/465, 424/474, 424/475, 424/479, 424/481, 424/485, 424/488, 424/493, 424/496, 424/500
• US Class Current: 424/474
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/606 having amino groups
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/286 Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Pharmaceutical compositions for orally delivering a therapeutically effective amount of a drug to the colon without significant release of the drug in the upper GI tract after oral administration of the composition are described. The composition is a unit dosage in the form of a tablet that comprises about 0.01% by weight to about 10% by weight of the drug that is useful in treating a colonic disorder or that is absorbed from the colon; about 40% by weight to about 98% by weight of a hydrocolloid gum obtainable from higher plants; and about 2% by weight to about 50% by weight of a pharmaceutically acceptable binder. The compositions are useful for treating lower GI disorders in human subjects by administering a suitable amount to a subject in need thereof. A particularly preferred aspect is the process for preparing such composition in the form of a tablet.

Claims

1. A pharmaceutical tablet having an inner composition optionally coated by a pharmaceutically-acceptable coating, said tablet designed for orally delivering a therapeutically effective amount of a drug to the lower GI tract without significant release of the drug in the upper GI tract after oral administration of the tablet, which inner composition of the tablet comprises

about 0.01% by weight to about 10.0% by weight of a drug useful for treating a lower GI tract disorder;

about 40% by weight to about 98% by weight of a hydrocolloid gum obtainable from higher plants; and

about 2% by weight to about 50% by weight of a pharmaceutically acceptable excipient;

no enteric polymeric material or gas-forming excipient, wherein the components of the inner composition are distributed so that the drug is concentrated in an active core with the gum and excipient surrounding the active core.

2. The tablet of claim 1, wherein said tablet is designed for orally delivering a therapeutically effective amount of a drug to the colon.

3. The tablet of claim 1, which is enterically coated.

4. The tablet of claim 3, wherein the drug is a corticosteroid.

5. The tablet of claim 4, wherein the corticosteroid is present in an amount of about 1% by weight to about 4% by weight of the inner composition.

6. The tablet of claim 5, wherein the corticosteroid is dexamethasone, budesonide, fluticasone, prednisone, prednisolone or hydrocortisone.

7. The tablet of claim 6, wherein the corticosteroid is micronized budesonide.

8. The tablet of claim 6 wherein the corticosteroid is micronized dexamethasone.

9. The tablet of claim 1, wherein the drug is 5-ASA.

10. The tablet of claim 1, wherein the drug is a peptide.

11. The tablet of claim 10, wherein the peptide is LHRH, growth hormone, vasopressin, insulin, calcitonin, glucagon, GHRH, relaxin, somatostatin, a cytokine or a lymphokine.

12. The tablet of claim 1, wherein the drug is a stimulant laxative.

13. The tablet of claim 12, wherein the drug is a bisacodyl.

14. The tablet of claim 1, wherein the hydrocofloid is guar gum, locust bean gum, gum tragacanth or karaya gum.

15. The tablet of claim 14, wherein the hydrocofloid is guar gum.

16. A method for treating a disorder of the lower GI tract in a human subject, which method comprises orally-administering to a human subject in need thereof a tablet of claim 1.

17. The method of claim 16, wherein the inner composition comprises

about 0.5% by weight to about 5.0% by weight of a drug useful in treating a colonic disorder;

about 50% by weight to about 70% by weight of a hydrocolloid gum obtainable from higher plants;

about 25% by weight to about 50% by weight of the pharmaceutically-acceptable excipient.

18. The method of claim 16, wherein the disorder is characterized by inflammation of the colon and the drug is a corticosteroid.

19. The method of claim 18, wherein the corticosteroid is present in an amount of about 1% by weight to about 4% by weight.

20. The method of claim 19, wherein the corticosteroid is dexamethasone, budesonide, fluticasone, prednisone, prednisolone or hydrocortisone.

21. The method of claim 16, wherein the drug is 5-ASA.

22. The method of claim 16, wherein the hydrocolloid is guar gum, locust bean gum, gum tragacanth or karaya gum.

23. The method of claim 22, wherein the hydrocolloid is guar gum.

24. A method for preferentially delivering a drug to the lower GI tract wherein such drug is susceptible to enzymatic degradation in the upper GI tract, which method comprises orally-administering to a human subject in need thereof a tablet of claim 1.

25. The method of claim 24, wherein the drug is a peptide.

26. The method of claim 25, wherein the peptide is LHRH, growth hormone, vasopressin, insulin, calcitonin, glucagon, GHRH, relaxin, somatostatin, a cytokine or a lymphokine.

27. The method of claim 25, wherein the peptide is nafarelin, busarelin, goserelin, leuprolide, or a pharmaceutically-acceptable salt thereof and is delivered to treat endometriosis in a female human subject.

28. The method of claim 16, wherein the disorder is constipation and the drug is a stimulant laxative.

29. The method of claim 16, wherein the disorder is characterized by inflammation of the colon and the drug is 5-ASA.

30. The tablet of claim 10, wherein the peptide is selected from the group consisting of nafarelin, busarelin, goserelin, leuprolide, and a pharmaceutically-acceptable salt thereof.