Claims
- 1. Clopidogrel hydrogensulfate characterized by data selected from the group consisting of: a powder X-ray diffraction pattern with peaks at about 8.3, 9.1, 23.2 and 23.6±0.2 degrees two-theta, a differential scanning calorimetric thermogram having an endothermic peak at about 136° C. and a FTIR spectrum with peaks at about 959, 1061, 1430, 1751, 1757 and 3119 cm−1.
- 2. Clopidogrel hydrogensulfate of claim 1 characterized by a differential scanning calorimetric thermogram having an endothermic peak at about 136° C.
- 3. Clopidogrel hydrogensulfate of claim 2 having a FTIR spectrum with peaks at about 959, 1061, 1430, 1751, 1757 and 3119 cm−1.
- 4. The clopidogrel hydrogensulfate of claim 3 further characterized by a FTIR spectrum as substantially depicted in FIG. 14.
- 5. Clopidogrel hydrogensulfate having of claim 3 having a powder X-ray diffraction pattern with peaks at about 8.3, 9.1, 23.2 and 23.6±0.2 degrees two-theta.
- 6. The clopidogrel hydrogensulfate of claim 5 further characterized by a powder X-ray diffraction pattern as substantially depicted in FIG. 12.
- 7. A process for preparing clopidogrel hydrogensulfate of claim 1 comprising the steps of:
a. preparing a solution of clopidogrel hydrogensulfate in 1-propanol, b. removing the 1-propanol from the solution to obtain a residue; c. admixing an antisolvent with the residue to precipitate clopidogrel hydrogensulfate; and d. separating the clopidogrel hydrogensulfate.
- 8. The process of claim 7, wherein removing is carried out by evaporation.
- 9. The process of claim 7, wherein the process results in a clopidogrel hydrogensulfate with a purity of at least about 99% as measured by area percentage with HPLC.
- 10. The process of claim 7, wherein the antisolvent is an ether.
- 11. The process of claim 10, wherein each alkyl radical of the ether is independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, 1-butyl, 2-butyl and t-butyl.
- 12. The process of claim 11, wherein the ether is diethyl ether.
- 13. The process of claim 7, wherein preparing a solution includes converting clopidogrel base to clopidogrel hydrogensulfate by contact with hydrosulfuric acid in 1-propanol.
- 14. The clopidogrel hydrogensulfate prepared by the process of claim 7.
- 15. A process for preparing clopidogrel hydrogensulfate Form II comprising the steps of:
a. preparing a solution of clopidogrel hydrogensulfate in a solvent selected from the group consisting of dichloromethane, 1,4-dioxane, toluene, chloroform, ethyl acetate, methylethyl ketone and t-butylmethyl ether; b. precipitating clopidogrel hydrogensulfate from the solution; and c. separating the clopidogrel hydrogensulfate.
- 16. The process of claim 15, wherein the solvent is dichloromethane.
- 17. The process of claim 15, wherein the solvent is 1,4-dioxane.
- 18. The process of claim 15, wherein the solvent is toluene.
- 19. The process of claim 15, wherein the solvent is chloroform.
- 20. The process of claim 15, wherein the solvent is ethyl acetate.
- 21. The process of claim 15, wherein the solvent is methylethyl ketone.
- 22. The process of claim 15, wherein the solvent is t-butylmethyl ether.
- 23. A process for preparing clopidogrel hydrogensulfate Form II comprising the steps of:
a. preparing a solution of clopidogrel hydrogensulfate in acetonitrile; b. admixing the solution with an antisolvent to precipitate clopidogrel hydrogensulfate; and c. separating the precipitate.
- 24. The process of claim 23, wherein the admixing involves addition of the solution to the antisolvent.
- 25. The process of claim 23, wherein the clopidogrel hydrogensulfate used to prepare the solution is amorphous clopidogrel hydrogensulfate.
- 26. The process of claim 23, wherein the antisolvent is an ether.
- 27. The process of claim 26, wherein each alkyl radical of the ether is independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, 1-butyl, 2-butyl and t-butyl.
- 28. The process of claim 27, wherein the ether is diethyl ether.
- 29. The process of claim 23, wherein preparing a solution includes converting clopidogrel base to clopidogrel hydrogensulfate by contact with hydrosulfuric acid in solvent of the resulting solution.
- 30. A pharmaceutical composition comprising clopidogrel hydrogensulfate Form VI, and a pharmaceutically acceptable excipient.
- 31. A method of inhibiting platelet aggregation comprising administering the pharmaceutical composition of claim 30.
- 32. Clopidogrel hydrogensulfate 1-propanolate.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/US02/40679 |
Dec 2002 |
WO |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application Ser. No. 10/074,409, filed on Feb. 12, 2002, and claims the priority of provisional application Ser. No. 60/348,182, filed Jan. 11, 2002 and 60/359,157, filed Feb. 21, 2002, and to PCT Application No. ______, filed Dec. 18, 2002, entitled “Polymorphs of Clopidogrel Hydrogensulfate,” [Attorney Docket No. 1662/58576], all of which are incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60348182 |
Jan 2002 |
US |
|
60359157 |
Feb 2002 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
10074409 |
Feb 2002 |
US |
Child |
10339008 |
Jan 2003 |
US |