Thermal stability of aripiprazole monohydrate investigated by Raman spectroscopy

Aripiprazole (7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyril) is a well-known antipsychotic oral drug, whose molecular structure makes it suitable for polymorphism. Several crystalline structures were reported in the literature including anhydrate, hydrate and solvate modifications. It was observed that aripiprazole monohydrate exhibits a complex dehydration dynamics which was not completely elucidated. In this work the dehydration process of the aripiprazole hydrate was investigated by using Raman scattering, hot-stage microscopy and differential scanning calorimetry. The temperature evolution of the Raman spectra was analyzed through the multivariate statistical method of principal component analysis. Our results support that the dehydration process of aripiprazole is divided into two steps. First a diffusion-controlled loss of water followed by a fast nucleation and crystallization of the anhydrous form.