Coprecipitation of hydrochlorothiazide/PVP for the dissolution rate improvement by precipitation with compressed fluid antisolvent process

Hydrochlorothiazide (HCT) and HCT/polyvinylpyrrolidone (PVP) mixtures were processed using precipitation with compressed fluid antisolvent process under sub- and supercritical conditions. When HCT was precipitated alone, severely agglomerated and irregular microparticles were obtained. On the other hand, coprecipitates were produced as spherical nanoparticles as small as 52.3 nm. HR-TEMand the dissolution tests revealed that these spherical nanoparticles are PVP particles that contain HCT. Particle size and the dissolution rate of HCT dispersed in the PVP particles greatly improved compared to those of unprocessed and neat HCT precipitates. Two nucleation mechanisms, homogenous and heterogeneous nucleation, can explain the phenomena. High normalized drug loadings and precipitation yields support heterogeneous nucleation theory in which PVP precipitated first, allowing the nucleation of HCT particles on the surface of PVP particles. (C) 2017 Elsevier B.V. All rights reserved.