Claims
- 1. A compound of formula
- 2. A pharmaceutical composition comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 3. The composition of claim 2 which is free of form stabilizers.
- 4. The composition of claim 2 which is free of ionic polymers.
- 5. A method of making a compound of claim 1 comprising:
(a) dissolving crystalline compound of formula I in an organic solvent; and (b) precipitating the desired amorphous compound of formula I from the solution of step (a).
- 6. The method of claim 5 wherein the organic solvent used in step (a) is selected from the group consisting of ethanol, methanol, acetone, dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide, N-methylpyrrolidone, diethylene glycol ethyl ether, glycofural, propylene carbonate, tetrahydrofuran, polyethylene glycols, and propylene glycols.
- 7. The method of claim 6 wherein the organic solvent used in step (a) is dimethylacetamide.
- 8. The method of claim 5 wherein precipitation in step (b) is effected by adding the solution of step (a) to a cold aqueous solution.
- 9. The method of claim 8 wherein the temperature of the aqueous solution is from about 2° C. to about 10° C.
- 10. The method of claim 9 wherein the pH of the aqueous solution is one in which the compound of formula I in amorphous form is not soluble.
- 11. The method of claim 10 wherein the pH of the aqueous solution is from about 2 to about 7.
- 12. A method of making a compound of claim 1 comprising:
(a) dissolving a compound of formula I in crystalline form in an organic solvent; and (b) removing the organic solvent.
- 13. The method of claim 12 wherein the organic solvent is selected from the group consisting of ethanol, methanol, acetone, dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide, N-methylpyrrolidone, diethylene glycol ethyl ether, glycofural, propylene carbonate, tetrahydrofuran, polyethylene glycols, and propylene glycols.
- 14. The method of claim 12 wherein the organic solvent is removed by spray drying.
- 15. The method of claim 12 wherein the organic solvent is removed by lyophilization.
- 16. A method of making a compound of claim 1 comprising:
(a) dissolving a crystalline compound of formula I in a supercritical fluid; and (b) removing the supercritical fluid.
- 17. The method of claim 15 wherein the supercritical fluid is liquid nitrogen or liquid carbon dioxide.
- 18. A method of making a compound of claim 1 comprising:
(a) dissolving a crystalline compound of formula I in an organic solvent; and (b) extracting the organic solvent from the solution resulting in step (c) with a supercritical fluid as indicated in step 16.
- 19. A method of making a compound of claim 1, comprising:
(a) continuously exposing a crystalline compound of formula I to a temperature-controlled extruder (hot melt extruder) that is set at different temperature gradients; and (b) rapidly cooling the extrudate from step (a).
Parent Case Info
[0001] This application claims priority to prior provisional application Ser. No. 60/237,563, filed on Oct. 3, 2000 claimed under 35 U.S.C. § 119(e).
Provisional Applications (1)
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Number |
Date |
Country |
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60237563 |
Oct 2000 |
US |