Preparation of resveratrol nanocrystals by drug/polymer/surfactant ternary hot extrusion

Abstract

Drug nanocrystal formulations are an effective strategy for dissolution improvement and oral absorption of poorly water-soluble drugs. In our previous study, we developed a ternary hot extrusion method and demonstrated that drug nanocrystal suspensions can be successfully prepared. In this study, resveratrol (RES) was used as a model poorly water-soluble drug to evaluate the feasibility of this method. A ternary system consisting of RES, polyvinylpyrrolidone K-25 (PVP), and sodium dodecyl sulfate (SDS) was investigated. Physical mixtures (RES/PVP/SDS = 1:3:1 in the weight ratio) were processed using a twin-screw melt mixer to obtain hot extrudates (HE), which were subsequently dispersed in water. Powder X-ray diffraction (PXRD) analysis confirmed that RES remained crystalline in all HE samples. SDS decomposition was observed under high screw speeds (≥250 rpm) and elevated temperatures (130 °C). Cryogenic transmission electron microscopy revealed aggregates of rod-shaped RES nanocrystals (~50 nm) in the HE suspension. PXRD of ultracentrifuged precipitates of HE suspension confirmed that RES retained crystallinity within the nanoparticles. Nanoparticle formation efficiency depended strongly on processing conditions. At 120 °C, higher screw speeds reduced nanoparticle formation due to SDS degradation. At 200 rpm, increasing temperature improved the nanoparticle formation efficiency, reaching a maximum at 125 °C, followed by a decline at 130 °C due to SDS degradation. These results suggest that the optimal conditions for preparing RES nanosuspensions via hot extrusion involve employing relatively high screw rotation speeds and processing temperatures within a range preventing SDS decomposition. This study demonstrates the potential broad applicability of this technique for various poorly water-soluble drugs.