Patent ID: 8039621

Claim:
A process for preparing hygroscopic anhydrous aripiprazole having major peaks in an X-ray powder diffractogram substantially as shown in FIG. 1 comprising: (A) dissolving aripiprazole, or an acid salt thereof, in a water miscible organic solvent, optionally containing up to 50% water (by volume), with heating to form a solution of aripiprazole, or a solution of an acid salt thereof; (B) when the solution comprises a solution of an acid salt, adding a base to the solution in an amount sufficient to neutralize the acid salt; (C) optionally contacting the solution with decolorizing carbon or diatomaceous earth; (D) maintaining the temperature of the solution above about 70° C., and adding sufficient water to produce an aqueous organic solution containing at least 5% water (by volume); (E) cooling the aqueous organic solution, as required, to a temperature of 25 to 78° C. and seeding the solution with hygroscopic anhydrous aripiprazole crystals having major peaks in an X-ray powder diffractogram substantially as shown in FIG. 1 ; (F) agitating the aqueous organic solution at a temperature in the range of 25 to 78° C. to initiate crystallization and form a slurry containing aripiprazole crystals; (G) cooling the aripiprazole slurry with agitation to a temperature in the range of 15 to 25° C., and maintaining the slurry in that temperature range for at least 2 hours to complete crystal formation; (H) isolating the crystals by filtration and optionally washing the crystals with organic solvent; and (I) drying the isolated crystals under a vacuum and at a temperature of not greater than 80° C. until the isolated crystals contain less than about 1.0% water by weight.