Comparison of nanomilling and coprecipitation on the enhancement of in vitro dissolution rate of poorly water-soluble model drug aripiprazole

Abstract

The aim of this study was to evaluate the effect of coprecipitation and nanomilling on the crystallinity of a model drug, aripiprazole and evaluate the in vitro dissolution rate (IDR). Aripiprazole compositions were prepared by physical mixing, coprecipitation and nanomilling using hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP) K17 and pluronic F127. The particle size, solubility, IDR and drug crystallinity were studied. Aripiprazole pluronic compositions were compressed into tablets and dissolution rate was evaluated. The particle size of nanomilled compositions was significantly smaller than that of the other compositions. The saturation solubility of aripiprazole from nanoparticle (NP) and coprecipitate (CP) from PVP and Pluronic was comparable, however, NP of HPC containing composition showed higher solubility when compared to its CP compositions. The crystallinity of aripiprazole decreased from physical mixtures to coprecipitates and further in NPs. The increased aripiprazole IDR was due to decreased crystallinity from coprecipitate compositions and disruption of crystallinity from nanomilled compositions. Aripiprazole tablets prepared from nanomilled powder dissolved >75% within 10 min compared with 17% and 20% for tablets prepared from physical mixture and coprecipitate powders, respectively. The increase in IDR due to nanomilling was more significant than coprecipitation and NPs retained the IDR after compression into tablets.