Effervescent compositions comprising bisphosphonates and methods related thereto

• US 20060240103A1
• Filed: 06/23/2006
• Published: 10/26/2006
• Est. Priority Date: 03/06/2002
• Status: Abandoned Application

• Current Assignee: Christer Rosen, David Mccallister
• Original Assignee: Christer Rosen, David Mccallister
• Inventors: Rosen, Christer, McCallister, David
• Application Number:
  US11/473,044
• Publication Number:
  US 20060240103A1
• Time in Patent Office: Days
• US Class Current: 424/466
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence

Abstract

The invention provides effervescent composition comprising a bisphosphonate, an acidic compound, an alkaline effervescing component, and optionally an anti-ulcer agent and methods of treating osteoporosis in a mammal using the effervescent compositions.

Claims

1. An effervescent composition comprising:

(a) a bisphosphonate,

(b) an acid component, and

(c) an alkaline effervescing component,

wherein the composition when dissolved in water produces a solution having a buffered pH of about 3 to about 6.5.

2. The effervescent composition of claim 1, further comprising an anti-ulcer agent.

3. The composition of claim 2, wherein the anti-ulcer agent is an H₂-antagonist.

4. The composition of claim 3, wherein the H₂-antagonist is selected from the group consisting of ranitidine, cimetidine, famotidine, nizatidine, and combinations thereof.

5. The composition of claim 2, wherein the anti-ulcer agent is a proton pump inhibitor.

6. The composition of claim 5, wherein the proton pump inhibitor is selected from the group consisting of omeprazole, pantoprazole, lansoprazole, rabeprazole, and combinations thereof.

7. The composition of claim 2, wherein the anti-ulcer agent comprises at least one H₂-antagonist and at least one proton pump inhibitor.

8. The composition of claim 1, wherein the bisphosphonate is selected from the group consisting of etidronate, risedronate, ibandronate, alendronate, and combinations thereof.

9. The composition of claim 1, wherein the bisphosphonate is etidronate.

10. The composition of claim 1, wherein the bisphosphonate is alendronate.

11. The composition of claim 1, wherein the bisphosphonate is ibandronate.

12. The composition of claim 1, wherein the bisphosphonate is residronate.

13. The composition of claim 1, wherein the dissolved buffered solution is capable of mediating the pH of a patient'"'"'s stomach for at least about 15 minutes or more.

14. The composition of claim 1, wherein the acid component comprises citric acid.

15. The composition of claim 1, wherein the alkaline effervescing component comprises a carbonate salt and a bicarbonate salt.

16. The composition of claim 1, wherein the acid component and the alkaline effervescing component are at least partially reacted with each other during granulation with the bisphosphonate.

17. The composition of claim 1, further comprising a sweetener or flavorant.

18. The composition of claim 1, further comprising a solubilizing agent.

19. The composition of claim 18, wherein the solubilizing agent is selected from the group consisting of polyvinylpyrrolidones, polyethylene glycols, dextrans, and combinations thereof.

20. The composition of claim 1, wherein the acid component comprises a non-zero amount of acid equivalents and the solution comprises an amount of a fully deprotonated salt of the acid component that is at least about 1.5 times the amount of acid equivalents.

27. A method of treating osteoporosis in a mammal comprising:

(a) combining an osteoporosis-treating effective amount of the composition of claim 1 with water to form at least a partial solution; and

(b) administering the solution to the mammal orally.

28. The method of claim 27, wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.

29. The method of claim 27, wherein the composition is administered daily, weekly, twice weekly, thrice weekly, biweekly, monthly, or every other month.

30. The method of claim 27, wherein the bisphosphonate is alendronate, and the amount of the alendronate to be administered weekly is about 10 mg to about 15 mg.

31. The method of claim 27, wherein the bisphosphonate is alendronate, and the amount of the alendronate to be administered monthly is about 50 mg to about 120 mg.

32. The method of claim 27, wherein the bisphosphonate is alendronate, and the amount of the alendronate to be administered every other month is about 100 mg to about 300 mg.

33. A method of inhibiting bone resorption in a mammal comprising:

(a) combining a bone resorption inhibiting amount of the composition of claim 1 with water to form at least a partial solution, and

(b) administering the solution to the mammal orally.

34. The method of claim 33, wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.

21. An effervescent composition comprising:

(a) a bisphosphonate,

(b) an anti-ulcer agent,

(c) an acid component,

(d) an alkaline effervescing component, and, optionally, one or more of the following ingredients selected from;

(e) a sweetener,

(f) a flavorant, and

(g) a solubilizing agent.

22. The effervescent composition of claim 21, wherein the acid component and the alkaline effervescing component are at least partially reacted with each other during granulation with the bisphosphonate and/or the anti-ulcer agent.

23. The composition of claim 21, wherein the effervescent composition comprises:

(a) about 0.1% to about 19% bisphosphonate,

(b) about 0.5% to about 50% anti-ulcer agent,

(c) about 15% to about 60% acid component

(d) about 20% to about 70% alkaline effervescing component,

(e) about 0% to about 5% sweetener,

(f) about 0% to about 10% flavorant, and

(g) about 0% to about 10% solubilizing agent,

wherein the percent amounts are based on the total weight of the composition.

24. The composition of claim 23, wherein the bisphosphonate is etidronate.

35. A method of treating osteoporosis in a mammal comprising:

(a) combining an osteoporosis-treating effective amount of the composition of claim 21 with water to form at least a partial solution; and

(b) administering the solution to the mammal orally.

36. The method of claim 35, wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.

37. A method of inhibiting bone resorption in a mammal comprising:

(a) combining a bone resorption inhibiting amount of the composition of claim 21 with water to form at least a partial solution, and

(b) administering the solution to the mammal orally.

38. The method of claim 37, wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.

25. An effervescent composition comprising:

(a) a microencapsulated bisphosphonate,

(b) an acid component,

(c) an alkaline effervescing component, and optionally

(d) an anti-ulcer agent.

26. The effervescent composition of claim 25, wherein the bisphosphonate is microencapsulated in a cellulosic, gum, or wax coating.

39. A method of treating osteoporosis in a mammal comprising:

(a) combining an osteoporosis-treating effective amount of the composition of claim 25 with water to form at least a partial solution; and

(b) administering the solution to the mammal orally.

40. The method of claim 39, wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.

41. A method of inhibiting bone resorption in a mammal comprising:

(a) combining a bone resorption inhibiting amount of the composition of claim 25 with water to form at least a partial solution, and

(b) administering the solution to the mammal orally.

42. The method of claim 41, wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.