Polymorphs of atomoxetine hydrochloride
AssigneeTeva Pharmaceutical Fine Chemicals S.r.l.
InventorsJudith Aronhime, Stefano Bianchi, Eugenio Castelli, Paola Daverio, Silvia Mantovani, Adrienne Kovacsne-Mezei
Life of this patent
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Abstract
The present invention provides novel crystalline polymorph forms of atomoxetine hydrochloride denominated Forms B and C and methods for their preparation, as well as methods for the preparation of Form A. The present invention provides pharmaceutical compositions that comprise atomoxetine hydrochloride Form B, Form C, or mixtures thereof that can be used to treat attention deficit/hyperactivity disorder.
Claims42
A process for the preparation of a crystalline form of atomoxetine hydrochloride characterized by a powder x-ray diffraction pattern having peaks at about 13.7, 17.3, 18.7, 21.1, 22.6, 24.0, 27.3, 28.4 and 29.3±0.2 degrees two-theta comprising the steps of:
- a) combining atomoxetine hydrochloride Form B with acetone to obtain a mixture;
- and
- b) maintaining the mixture for a sufficient time to obtain the crystalline form of atomoxetine hydrochloride.
A process for the preparation of a crystalline form of atomoxetine hydrochloride characterized by a powder x-ray diffraction pattern having peaks at about 13.7, 17.3, 18.7, 21.1, 22.6, 24.0, 27.3, 28.4 and 29.3±0.2 degrees two-theta comprising the steps of:
- a) combining atomoxetine hydrochloride with water at a temperature of about 40° C. to about 60° C. to obtain a mixture;
- b) cooling the mixture to room temperature to obtain a precipitate;
- and
- c) recovering the crystalline atomoxetine hydrochloride.
A process for the preparation of a crystalline form of atomoxetine hydrochloride characterized by a powder x-ray diffraction pattern having peaks at about 13.7, 17.3, 18.7, 21.1, 22.6, 24.0, 27.3, 28.4 and 29.3±0.2 degrees two-theta comprising the steps of:
- a) combining atomoxetine hydrochloride with a solvent selected from water, methanol, and a mixture of acetic acid and ethyl acetate, at a temperature ranging from room temperature to about 60° C. to obtain a mixture;
- b) removing at least some of the solvent until a precipitate forms;
- and
- c) recovering atomoxetine hydrochloride Form A.
A process for the preparation of a crystalline form of atomoxetine hydrochloride characterized by a powder x-ray diffraction pattern having peaks at about 13.7, 17.3, 18.7, 21.1, 22.6, 24.0, 27.3, 28.4 and 29.3±0.2 degrees two-theta comprising the steps of:
- a) combining atomoxetine base in a solvent selected from C1-4 alcohol, C2-4 alkyl ester, C1-4 alkyl ether, mixtures thereof, and C1-6 substituted or unsubstituted aromatic hydrocarbon to obtain a mixture;
- b) combining the mixture with hydrochloric acid or hydrogen chloride to obtain a precipitate;
- and
- c) recovering atomoxetine hydrochloride Form A from the precipitate.
A crystalline form of atomoxetine hydrochloride, characterized by data selected from:
- an x-ray powder diffraction pattern having peaks at about 11.5, 17.1, 19.8, 21.3, 22.5, 23.6, 24.6, 27.5 and 28.5±0.2 degrees two-theta;
- and an infrared absorption spectrum having peaks at about 2761, 1596, 1493, 1234, 768, and 711 cm−1.
A crystalline form of atomoxetine hydrochloride, characterized by an x-ray powder diffraction pattern having peaks at about 10.1, 16.4, 18.2 and 25.1±0.2 degrees two-theta.
Dependencies are inferred from the claim text.