Design amorphous solid dispersion microparticle of aripiprazole in polyvinylpyrrolidone using the supercritical antisolvent process

Background

Aripiprazole is a poorly water-soluble antipsychotic drug with limited bioavailability due to its low dissolution rate. This study aimed to enhance its dissolution rate by designing and producing amorphous solid dispersion (ASD) microparticles using polyvinylpyrrolidone (PVP) as a polymeric excipient, utilizing the supercritical antisolvent (SAS) process.

Methods

To achieve a satisfactory ASD formulation, a mixed solvent system was screened for SAS operation. Additionally, the effects of various SAS parameters, including drug/polymer ratio, operating temperature, operating pressure, CO₂ flow rate, solution flow rate, nozzle diameter, and solution concentration, on the design of ASD microparticles were investigated. The solid-state properties of SAS-processed samples were compared with unprocessed aripiprazole and PVP through SEM, PXRD, DSC, and FTIR analyses.

Significant findings

By optimizing the SAS operating parameters, quasi-spherical ASD microparticles with a mean size of about 1 μm were successfully produced. The total powder recovery exceeded 90 %, and the total solution concentration could be increased up to 100 mg/ml to achieve high throughput. The dissolution rate study indicated that the dissolution of the SAS-produced ASD formulation was significantly enhanced approximately 29 times compared to the physical mixture of aripiprazole and PVP.