Low hygroscopic aripiprazole drug substance and processes for the preparation thereof

摘要

The present invention provides low hygroscopic forms of aripiprazole and processes for the preparation thereof which will not convert to a hydrate or lose their original solubility even when a medicinal preparation containing the anhydrous Aripiprazole crystals is stored for an extended period.

主权项

1. A process for the preparation of granules comprising wet granulating anhydrous aripiprazole crystals and one or more pharmaceutically acceptable carriers to obtain granules of said crystals, drying the obtained granules at 70 to 100° C., sizing the dried granules, and then drying the sized granules at 70 to 100° C. for 1 to 6 hours again,
wherein said crystals have low hygroscopicity, wherein said low hygroscopicity is defined as a moisture content of 0.40% or less after placing said for 24 hours in a desiccator maintained at a temperature of 60° C. and a humidity level of 100% and one or more of the properties chosen from:
a powder x-ray diffraction spectrum comprising characteristic peaks at 2θ=11.0°, 16.6°, 19.3°, 20.3°, and 22.1° using a Cu Kα x-ray;an infrared absorption spectrum comprising infrared absorption bands at 2945, 2812, 1678, 1627, 1448, 1377, 1173, 960, and 779 cm−1 on the IR (KBr) spectrum;an endothermic curve comprising an endothermic peak near about 141.5° C. in a thermogravimetric or differential thermal analysis (heating rate 5° C./min);an endothermic curve comprising an endothermic peak near about 140.7° C. in differential scanning calorimetry analysis (heating rate 5° C./min); anda mean particle size of 50 μm or less.