Teva Pharmaceutical Industries Limited

Rami Lidor-Hadas

Judith Aronhime

Revital Lifshitz-Liron

Shlomit Wizel

Eti Kovalevski-Ishai

Valerie Niddam-Hildesheim

Revital Lifshitz

Sharon Avhar-Maydan

Zvi Harel

Eti Kovalevski

Sharon Avhar Maydan

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.

Polymorphs of clopidogrel hydrogensulfate

Provided is a novel method of making bisphosphonic acids, e.g. risedronic acid, including the step of combining a carboxylic acid, phoshorous acid, and a halophosphorous compound in the presence of a diluent that is an aromatic hydrocarbon or a silicone fluid. When the diluent is an aromatic hydrocarbon, a inert support or ortho-phosphoric acid codiluent is advantageously included.

Process for making bisphosphonic acids using diluents other than halogenated hydrocarbons

Processes for preparing a calcium salt of a statin from an ester derivative or protected ester derivative of the statin by using calcium hydroxide are provided. The ester or protected ester derivative is contacted with calcium hydroxide to obtain the calcium salt. Preferred statins are rosuvastatin, pitavastatin and atorvastatin, simvastatin and lovastatin. In processes beginning with a protected statin ester derivative, the protecting group is hydrolyzed during salt formation by contact with calcium hydroxide, or is contacted with an acid catalyst followed by contact with calcium hydroxide.

Processes for preparing calcium salt forms of statins

The present invention provides new crystalline Forms III, IV and V of clopidogrel hydrogensulfate and the amorphous form of clopidogrel hydrogensulfate, as well as their pharmaceutical compositions, and method of treatments with such compositions. The present invention also provides novel processes for preparation of clopidogrel hydrogensulfate Form I, Form III, Form IV, Form V and the amorphous form. The present invention further provides a novel process where the amorphous form is converted to Form I by contacting Form I with an ether.

CRYSTAL FORMS III, IV, V, AND NOVEL AMORPHOUS FORM OF CLOPIDOGREL HYDROGENSULFATE, PROCESSES FOR THEIR PREPARATION, PROCESSES FOR THE PREPARATION OF FORM I, COMPOSITIONS CONTAINING THE NEW FORMS AND METHODS OF ADMINISTERING THE NEW FORMS

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Kfar Saba, Israel

Rami Lidor-Hadas