Enhancement of Wettability and Dissolution Properties of Cilostazol Using the Supercritical Antisolvent Process: Effect of Various Additives

Abstract

The aim of this study was to improve wettability and dissolution rate of a poorly water-soluble drug, cilostazol, using the supercritical antisolvent (SAS) process. The solid state of particles precipitated from dichloromethane containing additives, including poloxamer 188, poloxamer 407, TPGS 1000, Gelucire^® 44/14 and Gelucire^® 50/13, in supercritical CO₂ medium were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), FT-IR, particle size analysis, contact angle, and dissolution. Interestingly, the morphology of SAS particles processed with TPGS 1000, Gelucire^® 44/14 and Gelucire^® 50/13 changed to plate- or leaflet-shaped. Furthermore, the particle sizes of cilostazol processed with Gelucire^® 44/14 and Gelucire^® 50/13 were increased compared to cilostazol processed without additives. Poloxamer 188 and poloxamer 407 were superior in increasing the dissolution rate due to decreased particle size, the resulting increased surface area, and improved wettability. Micronization with the supercritical antisolvent process resulted in a significant decrease in mean particle size, and wettability of cilostazol was increased by using small amounts of hydrophilic additives.