Nanosuspension with improved saturated solubility and dissolution rate of cilostazol and effect of solidification on stability

Abstract

The aim of the study was to formulate cilostazol containing nanosuspension by top-down wet milling method in order to increase the in vitro solubility and dissolution rate of this substance. The investigation of formulation parameters (emulsifier type, concentration, and combination of surface-active agents) on the milling efficiency was also brought into focus. The wet-milled and unmilled suspensions were applied onto solid carriers, and matrix pellets were prepared by extrusion/spheronization method. The reconstitution of nanoparticles from solid dosage forms was successful. Particle size reduction had a major impact on maximal thermodynamic solubility of cilostazol at pH = 1.2 and demonstrated a two times improvement compared to raw, unmilled surfactant dispersion. A significant effect on the highest dissolution rate constants at pH = 1.2 compared to raw, unmilled surfactant dispersion. Solid-state characterization of pulverized matrix pellets with differential scanning calorimetry and powder X-ray diffractometry indicated the transition of cilostazol Form A to amorphous form due to the extrusion process.