Optimization of supercritical fluid processes for aripiprazole nanoparticle production using GAS-antisolvent...

Particle size reduction makes drugs more soluble and bioavailable in the body. Researchers are increasingly interested in supercritical fluid processes for the production of micro- and nanoparticles in pharmaceuticals. In this research, gas anti-solvent (GAS), polyvinyl pyrrolidone polymer (PVP), and dimethyl sulfoxide (DMSO) solvent processes were used for the first time to produce aripiprazole (antipsychotic drug) nanoparticles. This specific combination has not been previously reported for aripiprazole and represents the main novelty of the study. The effects of different operating conditions were evaluated using a Box-Behenken design, which also sought to highlight the optimal combinations of conditions to obtain the smallest particle size. The effects of temperature (308, 318, and 328 K), pressure (10, 13, and 16 MPa), and APZ/PVP ratio (1, 5, and 9 w/w) on particle size were investigated. The optimum values of temperature, pressure, and APZ/PVP ratio were 312 K, 16 MPa, and 1w/w, respectively, which resulted in the minimum particle size. FTIR, FESEM, DLS, XRD, DSC, and dissolution rate tests were used to investigate changes in physical - chemical properties. Good results were obtained by reducing the particle size from 104.6 ± 30.1 μm to 389.6 ± 24.2 nm at optimum condition.