Polymorphs of clopidogrel hydrogensulfate
AssigneeTeva Pharmaceutical Industries Ltd.
InventorsRevital Lifshitz-Liron, Eti Kovalevski-Ishai, Shlomit Wizel, Sharon Avhar-Maydan, Rami Lidor-Hadas
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Abstract
Provided are new crystalline Forms III, IV, V and VI of clopidogrel hydrogensulfate and the amorphous form of clopidogrel hydrogensulfate, as well as their pharmaceutical compositions, and method of treatments with such compositions. Also provided are novel processes for preparation of clopidogrel hydrogensulfate Form I, Form II, Form III, Form IV, Form V, Form VI and amorphous form.
Claims32
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.
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.
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.
A pharmaceutical composition comprising clopidogrel hydrogensulfate Form VI, and a pharmaceutically acceptable excipient.
Clopidogrel hydrogensulfate 1-propanolate.
Dependencies are inferred from the claim text.