Crystalline polymorphic forms of olopatadine hydrochloride and processes for their preparation

An olopatadine hydrochloride comprising;

• an olopatadine hydrochloride Form A, wherein said olopatadine hydrochloride Form A is characterized by an XRD (2Θ) spectrum having characteristic peaks at approximately 6.28°, 10.92°, 12.72°, 15.55°, 17.58°, 18.26°, 18.94°, 19.39°, 20.64°, 24.14°, 25.49° and 28.32°.

(canceled)

An olopatadine hydrochloride comprising;

• an olopatadine hydrochloride Form B, wherein said olopatadine hydrochloride Form B is characterized by an XRD (2Θ) spectrum having characteristic peaks at approximately 10.44°, 12.93°, 14.81°, 18.53°, 19.20°, 19.44°, 20.96°, 22.99° and 28.76°.

At least one of olopatadine hydrochloride Form A and B having less than approximately 0.5% by area percentage HPLC of olopatadine trans isomer.

Olopatadine hydrochloride having a bromide content of less than approximately 1000 ppm as determined by ion chromatography.

A process for obtaining crystalline olopatadine hydrochloride comprising

• (i) treating olopatadine hydrochloride with at least one of an organic solvent, water and mixtures thereof and
• (ii) precipitating olopatadine hydrochloride crystals from the treated solution.

A process for obtaining olopatadine hydrochloride having less than approximately 0.5% by area percentage HPLC of its trans isomer comprising treating olopatadine hydrochloride with at least one of an alcoholic solvent, water and mixtures thereof.

A process for preparing olopatadine hydrochloride comprising performing a Wittig reaction, wherein said Wittig reaction comprises the use of at least one of hexyllithium, sodium hydride and combinations thereof.

A process for preparing olopatadine comprising performing a Grignard reaction, wherein said Grignard reaction comprises reacting 11-oxo-6,11-dihydrodibenzo [b,e]oxepin-2-yl)acetic acid with 3-dimethylaminopropylmagnesium chloride.