Designing amorphous solid nanoparticle dispersion of sulfadiazine in polyvinylpyrrolidone using supercritical CO2 as the antisolvent

Abstract

Designing and preparing amorphous solid dispersion (ASD) nanoparticles of poorly water-soluble active pharmaceutical ingredients is an efficient formulation approach to overcome the limitation of dissolution rate and bioavailability. This study aimed to demonstrate the feasibility of producing ASD nanoparticles of a poorly water-soluble antibiotic, sulfadiazine, in a polymeric carrier, polyvinylpyrrolidone (PVP), using supercritical CO₂ as the antisolvent (SAS). By three-stage investigations for neat sulfadiazine, neat PVP, and sulfadiazine/PVP system, the appropriate operating region for ASD design was reported, and the impact of various operating parameters on nanoparticle production was discussed. The comparison of solid-state properties of CO₂-processed samples was systematically investigated by SEM, PXRD, DSC, and FTIR analysis. At the optimal conditions, spherical ASD nanoparticles of sulfadiazine and PVP with a mean size of about 750 nm were successfully produced. In addition, the dissolution rate of the SAS-produced ASD formulation was considerably enhanced compared to that of the physical mixture of sulfadiazine and PVP. These results indicate that the supercritical CO₂ process efficiently produced ASD nanoparticles of sulfadiazine and PVP with improved dissolution behavior, total powder recovery above 80 %, and total concentration of up to 100 mg/mL.