Venlafaxine hydrochloride crystallisation process.
Publication Date: 2004-Jun-15
The IP.com Prior Art Database
Isabel Lloveras: AUTHOR [+1]
A Venlafaxine hydrochloride crystallisation process is described to obtain pure polymorphic Form II. Several solvents have been studied. X-Ray diffractogram enclosed.
Venlafaxine, (±)-1-[2-(Dimethylamino)-1-(4-ethoxyphenyl)ethyl]cyclohexanol, having the following formula, is an anti-depressant and acts inhibiting uptake of norepinephrine and serotonin.
Process for the preparation of Venlafaxine hydrochloride is described in EP0112669. The hydrochloride salt is desirable since it enables Venlafaxine to be conveniently formulated.
It has been reported that Venlafaxine hydrochloride can exist in different crystalline polymorphic forms (US6274171, EP1334082, EP1330427). Although any of the polymorphic forms such as Form I and Form II may be used in the formulations of Venlafaxine hydrochloride, Form II is preferred for having higher particle size with better filtration and drying characteristics than Form I.
Known Venlafaxine hydrochloride Form II exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks at degrees 2θ:
6.7, 10.2, 13.5, 15.5, 18.2, 19.8, 20.3, 21.7, 22.6, 25.6, 28.1, 35.1 ±0.2.
It has been described different processes to prepare Venlafaxine hydrochloride Form II (dry, slurry and crystallisation) but there is still a need to produce Venlafaxine in a reproducible, pure and crystalline form to enable formulations to meet exacting pharmaceutical requirements and specifications.
We have now seen that the crystallisation is the best process to assure pure Form II having a reproducible particle size distribution at industrial scale. We have studied different solvents in the preparation of Venlafaxine hydrochloride Form II.
Venlafaxine hydrochloride Form II can be obtained by
- dissolving Venlafaxine hydrochloride in an organic solvent or in a mixture of organic solvents at elevated temperature
- cooling the solution to metastable zone
- adding seeding crystals, preferably 4-8% of the quantity of Ve...