Modified calcium phosphate excipient

• US 20050031682A1
• Filed: 07/02/2004
• Published: 02/10/2005
• Est. Priority Date: 07/07/2003
• Status: Active Grant

• Current Assignee: Synthon Ip Incorporated (Synthon International Holding BV)
• Original Assignee: Synthon Ip Incorporated (Synthon International Holding BV)
• Inventors: Cucala Escoi, Joan, Gallego Luengo, Montserrat, Siles Ortega, Arturo
• Granted Patent: US 7,364,755 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates

Abstract

Calcium phosphate modified with a fatty acid wax in a weight ratio of 50:50 to 95:5, respectively, is useful as an excipient.

Claims

1. An excipient composition comprising calcium phosphate modified with a fatty acid wax, wherein a weight ratio of said calcium phosphate to said wax is within the range of 50:

50 to 95;

5.

2. The excipient composition according to claim 1, wherein said weight ratio of calcium phosphate:

wax is within the range of 60;

40 to 85;

15.

3. The excipient composition according to claim 1, wherein said wax is selected from the group consisting of palmitic acid, behenic acid, stearic acid, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, and mixtures thereof.

4. The excipient composition according to claim 3, wherein said wax is glyceryl behenate.

5. The excipient composition according to claim 4, wherein said weight ratio of calcium phosphate to glyceryl behenate is within the range of 60:

40 to 85;

15.

6. The excipient composition according to claim 1, wherein said calcium phosphate is an anhydrous dibasic calcium phosphate.

7. The excipient composition according to claim 1, wherein said excipient composition is in a particulate form.

8. The excipient composition according to claim 7, wherein said particles have an average size within the range of 50 to 500 microns.

9. The excipient composition according to claim 8, wherein the average size of said particles is within the range of 125 to 250 microns.

10. The excipient composition according to claim 8, wherein said particulate form is substantially monodisperse such that at least 50% of said particles have a size within 20 microns of the average particle size.

11. The excipient composition according to claim 8, wherein said composition has an angle of repose within the range of 20°

to 40°

.

12. A solid dosage form comprising an effective amount of an active agent and the excipient composition according to claim 1.

13. The solid dosage form according to claim 12, wherein said active agent is a pharmaceutically active agent.

14. The solid dosage form according to claim 13, wherein said form is a tablet.

15. The solid dosage form according to claim 14, wherein said excipient composition is contained in said tablet in an amount of at least 40% by weight.

16. The solid dosage form according to claim 15, wherein said amount of excipient composition is at least 70% by weight.

17. The solid dosage form according to claim 14, wherein said excipient composition and said pharmaceutically active agent taken together total an amount that is at least 85% of said tablet by weight.

18. The solid dosage form according to claim 19, wherein said form is encapsulated in a capsule.

19. A process for making a tablet, which comprises:

dry mixing said excipient composition according to claim 1 with an active agent and optionally one or more excipients to form a tablet blend; and

compressing at least a portion of said tablet blend into a tablet.

20. The process according to claim 19, wherein said tablet is a modified release tablet.

21. The process according to claim 20, which further comprises coating said tablet with an enteric coating.

22. A process, which comprises:

granulating said excipient composition according to claim 1 with an active agent to form an active granulate; and

compressing at least a portion of said active granulate, optionally with additional excipients, into a tablet.

23. The process according to the claim 22, wherein said granulating step comprises wet granulating said active agent with said excipient composition.

24. A process, which comprises coating calcium phosphate particles with a fatty acid wax to form a modified calcium phosphate in particulate form having a weight ratio of calcium phosphate to wax within the range of 50:

50 to 95;

5, respectively.

25. The process according to claim 24, wherein said coating step comprises melt granulation of said calcium phosphate and said wax to form a granulate.

26. The process according to claim 25, wherein said melt granulation brings the wax to a maximum temperature within the range of 5°

C. below the wax melting point to 2°

C. above the wax melting point.

27. The process according to claim 25, wherein said wax and calcium phosphate are heated with at least microwave energy.

28. The process according to claim 25, wherein said wax is selected from the group consisting of palmitic acid, behenic acid, stearic acid, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, and mixtures thereof.

29. The process according to claim 28, wherein said wax is glyceryl behenate.

30. The process according to claim 29, wherein said calcium phosphate and said glyceryl behenate are present in a weight ratio of calcium phosphate:

wax that is within the range of 60;

40 to 85;

15.

31. The process according to claim 30, wherein said calcium phosphate is an anhydrous dibasic calcium phosphate.

32. The process according to claim 31, wherein said granulate has an average size within the range of 50 to 500 microns.

33. The process according to claim 32, said granulate has an average size within the range of 125 to 250 microns.

34. The process according to claim 25, wherein said granulate is free flowing.

35. A granulate made by the process of claim 30.

36. A particle, consisting essentially of a calcium phosphate particle having a fatty acid wax at least partially coated thereon, impregnated therein, or both;

said particle having a size within the range of 125 to 250 microns and said calcium phosphate and said wax present in a weight ratio of calcium phosphate;

wax that is within the range of 50;

50 to 95;

5.