Micronization of Clozapine Particles Using Rapid Expansion of Supercritical Solution with Solid Cosolvent (RESS-SC) Process

The rapid expansion of a supercritical solution (RESS) process has limited commercial applicability due to the extremely low solubility of polar drugs in supercritical CO2 (sc CO2). To overcome this major limitation, a modified process of rapid expansion of supercritical solution with solid cosolvent (RESS-SC) is proposed. Here, the RESS-SC is examined for clozapine using menthol solid as a cosolvent to reduce particle size and to increase drug solubility. In addition, the effect of extraction pressure and extraction temperature was investigated on the size and morphology of precipitated particles of clozapine. The properties of the micronized clozapine were assessed using scanning electron microscopy (SEM) and powder x-ray diffraction (XRD) techniques. In this study, the average particle size of clozapine was reduced from 29.15 (before RESS-SC) to 3.15 μm (after RESS-SC).