New Cocrystals of Antipsychotic Drug Aripiprazole: Decreasing the Dissolution through Cocrystallization

Cocrystallization is an important route to tuning the solubility in drugs development, including improving and reducing. Five cocrystals of aripiprazole (ARI) with resveratrol (RSV) and kaempferol (KAE), ARI-RSV, ARI(2)-RSV1 center dot MeOH, ARI-KAE, ARI-KAE center dot EtOH, ARI-KAE center dot IPA, were synthesized and characterized. The single crystal of ARI(2)-RSV1 center dot MeOH, ARI-KAE center dot EtOH, and ARI-KAE center dot IPA were analyzed by single crystal X-ray diffraction (SCXRD). The SCXRD showed multiple intermolecular interactions between API and the coformers, including hydrogen bond, halogen bond, and pi-pi interactions. Dissolution rate of the two nonsolvate ARI-RSV and ARI-KAE cocrystals were investigated through powder dissolution experiment in pH = 4.0 acetate buffer and pH = 6.8 phosphate buffer. The result showed that RSV could reduce the dissolution rate and solubility of ARI in both medium through cocrystallization. However, KAE improved the dissolution rate and solubility of ARI in pH = 4.0 medium, on the contrary, the two solubility indicators of ARI were both reduced for ARI-KAE cocrystal.

Automated summary

This study investigated the impact of cocrystallization on drug dissolution rate, showing that resveratrol could decrease the dissolution rate and solubility of aripiprazole, while kaempferol increased the dissolution rate under certain conditions. Different cocrystal forms also led to varied effects on drug solubility indicators.