Preparation, characterization, and evaluation of the co-amorphous systems of dasatinib to improve its pharmaceutical attributes†

Abstract

Synthesizing co-amorphous systems is one of the most promising approaches to enhance the solubility and dissolution rate of pharmaceuticals as well as to improve their oral bioavailability. Herein, we screened eleven co-formers to form co-amorphous systems with an active pharmaceutical ingredient (API), dasatinib (DAS), to increase the drug's solubility and dissolution rate. The liquid-assisted grinding method was used to prepare the systems, and a series of techniques, including powder X-ray diffractometry (PXRD), solid-state nuclear magnetic resonance (SSNMR), differential scanning calorimetry (DSC), modulated DSC, and Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), was used for characterization. Formation of co-amorphous systems of DAS with malic acid (MAL) and succinic acid (SU) was confirmed. Solid-state NMR confirmed the presence of intermolecular H-bonding in DAS : SU, and its absence in the DAS : MAL system, which explained the recrystallization of the DAS : SU system within 30 days. Physical stability assessment under high humidity and temperature conditions led to enhanced re-crystallization of DAS : SU, while the DAS : MAL system retained its amorphous nature. Finally, the DAS : MAL co-amorphous system showed significant improvement in solubility and dissolution compared with crystalline DAS. These results show that the co-amorphous system of DAS : MAL exhibited enhanced solubility and dissolution compared with crystalline DAS and demonstrated stability under different conditions.