Stable pharmacologically active compositions including vitamin D-containing and corticosteroid compounds with low pH compatibility

• US 20080064669A1
• Filed: 08/29/2007
• Published: 03/13/2008
• Est. Priority Date: 08/29/2006
• Status: Abandoned Application

• Current Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Cohen, Rakefet, Fox, Michael
• Application Number:
  US11/897,540
• Publication Number:
  US 20080064669A1
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• 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 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Provided are pharmaceutical compositions comprising at least one vitamin D-containing compound, at least one corticosteroid compound, and at least one solvent component selected from the group consisting of triglycerides, sorbitan, sorbitan fatty esters, cetearyl glucoside, PEG-n sorbitan stearate, acrylamide/sodium acryloyldimethyl taurate copolymers, and mixtures thereof. Also provided are methods of making such compositions, and methods for treating psoriasis using such compositions.

Claims

1. A pharmaceutical composition for topical use comprising an admixture of at least one vitamin D-containing compound, at least one corticosteroid compound, and at least one solvent component selected from the group consisting of a triglyceride, sorbitan, sorbitan fatty ester, cetearyl glucoside, PEG-n sorbitan stearate, acrylamide/sodium acryloyldimethyl taurate copolymer, and mixtures thereof.

2. The composition of claim 1 wherein the vitamin D-containing compound is an anhydrate.

3. The composition of claim 1 wherein the vitamin D-containing compound is in a hydrated form.

4. The composition of claim 1, wherein the at least one vitamin D-containing compound includes calcipotriene.

5. The composition of claim 2, wherein the at least one vitamin D-containing compound is calcipotriene anhydrate.

6. The composition of claim 3, wherein the at least one vitamin D-containing compound comprises at least about 50% calcipotriene anhydrate by weight.

7. The composition of claim 1, wherein the at least one corticosteroid compound includes betamethasone.

8. The composition of claim 1, wherein the at least one corticosteroid compound includes betamethasone dipropionate.

9. The composition of claim 1, wherein the at least one solvent component includes at least one of a medium chain triglyceride or polysorbate.

10. The composition of claim 1, wherein the at least one vitamin D-containing compound comprises calcipotriene anhydrate, and the at least one corticosteroid component comprises betamethasone dipropionate.

11. The composition of claim 1 further comprising paraffin, medium chain triglyceride, and tocopherol.

12. The composition of claim 1 further comprising paraffin, polysorbate, and tocopherol.

13. The composition of claim 1 having a stability profile which includes one or more of the following:

(a) the amount of the vitamin D-containing compound and the amount of corticosteroid compound in the composition do not decrease after the composition is stored at 40°

C. for three months;

or

(b) the amount of the vitamin D-containing compound and the amount of the corticosteroid compound in the composition do not decrease after the composition is stored at 55°

C. for 3 days.

14. The composition of claim 1, wherein:

(a) the amount of the vitamin D-containing compound and the amount of the corticosteroid compound in the composition is stable after the composition is stored at 40°

C. for three months; and

(b) the amount of the vitamin D-containing compound and the amount of the corticosteroid compound in the composition is stable after the composition is stored at 55°

C. for 3 days.

31. Use of a composition according to claim 1 for the manufacture of a medicament for treating psoriasis

15. A method for preparing a pharmaceutical composition for topical use comprising combining at least one vitamin D-containing compound, at least one corticosteroid compound, and at least one solvent component selected from the group consisting of triglycerides, sorbitan, sorbitan fatty esters, cetearyl glucoside, PEG-n sorbitan stearate, acrylamide/sodium acryloyldimethyl taurate copolymers, and mixtures thereof to form the composition.

16. The composition of claim 15 wherein the vitamin D-containing compound is an anhydrate.

17. The method of claim 15, further comprising combining at least one of an antioxidant, a stiffening agent, or a preservative.

18. The method of claim 15, wherein the at least one vitamin D-containing compound comprises calcipotriene.

19. The method of claim 15, wherein the at least one vitamin D-containing compound is calcipotriene anhydrate.

20. The method of claim 15, wherein the at least one vitamin D-containing compound includes at least about 50% calcipotriene anhydrate by weight.

21. The method of claim 15, wherein the at least one corticosteroid compound comprises betamethasone.

22. The method of claim 15, wherein the at least one corticosteroid compound includes betamethasone dipropionate.

23. The method of claim 15, wherein the at least one solvent component includes at least one of a medium chain triglyceride or a polysorbate.

24. The method of claim 15, wherein the at least one vitamin D-containing compound includes calcipotriene anhydrate, and the at least one corticosteroid compound includes betamethasone dipropionate.

25. The method of claim 15 comprising dissolving the vitamin D-containing compound in at least one solvent component, and combining with the corticosteroid compound.

26. The method of claim 15 further comprising the steps of:

(a) preparing a mixture of the at least one vitamin D-containing compound, the at least one solvent component, and paraffin;

(b) preparing a mixture of the at least one corticosteroid compound and mineral oil; and

(c) combining the mixtures of steps (a) and (b) to form the composition.

27. The method of claim 15 further comprising the steps of:

(a) preparing a mixture of calcipotriene, at least one of a medium chain triglyceride or polysorbate, and melted paraffin;

(b) preparing a mixture of betamethasone dipropionate, tocopherol and paraffin; and

(c) combining the mixtures of steps (a) and (b) to form the composition.

28. The method of claim 15, wherein the composition has at least one of the following stability profiles:

(a) the amount of the vitamin D-containing compound and the amount of corticosteroid compound in the composition do not decrease after the composition is stored at 40°

C. for three months;

or

(b) the amount of the vitamin D-containing compound and the amount of the corticosteroid compound in the composition do not decrease after the composition is stored at 55°

C. for 3 days.

29. The method of claim 15, wherein:

(a) the amount of the vitamin D-containing compound and the amount of corticosteroid compound in the composition do not decrease after the composition is stored at 40°

C. for three months; and

(b) the amount of the vitamin D-containing compound and the amount of the corticosteroid compound in the composition do not decrease after the composition is stored at 55°

C. for 3 days.

30. A composition prepared according to the method of claims 15.