Long-acting injectable microsphere of crosslinked collagen encapsulates solid dispersion to enhance bioavailability...

Aripiprazole (APZ) injectable formulations have been developed to address the poor patient compliance associated with their oral dosage forms for the long-term treatment of schizophrenia. However, the solubility of APZ decreases as the pH increases, which limits its bioavailability when administered via intramuscular injection. Herein, we developed injectable microspheres consisting of a polyvinylpyrrolidone (PVP)-based APZ solid dispersion encapsulated in crosslinked collagen (APZ@PVP@CC) to solve the aforementioned problem. The preparation process for PVP-based APZ solid dispersion (APZ@PVP) was optimized using single-axial electrospraying. The resulting solid dispersion increased the solubility of APZ by 15-fold and enhanced the in vitro release rate. Crosslinked collagen (CC) was synthesized and coated onto APZ@PVP using coaxial electrospraying. The structural and physicochemical properties of APZ@PVP@CC were characterized using scanning electron microscope and X-ray diffraction. APZ@PVP@CC exhibited sustained release behavior over a period of 30 d, with the release kinetics fitted the Hixson-Crowell model, suggesting that the drug release was governed by surface erosion rather than simple diffusion. APZ@PVP@CC did not exhibit cytotoxicity. The pharmacokinetic study in New Zealand rabbits demonstrated that APZ@PVP@CC maintained long-acting release for 30 d and enhanced bioavailability by 225% compared to the APZ grinding microcrystallites. In conclusion, APZ@PVP@CC provides a modified option for the schizophrenia treatment.