Solubility and Micronization of Griseofulvin in Supercritical CO2 with Cosolvent Acetone

Griseofulvin (GF) is an antifungal drug whose pharmaceutical activity can be improved by particle size reduction. In this study the rapid expansion of supercritical solution (RESS) was employed to micronize GF. Carbon dioxide (CO2) with cosolvent acetone was chosen as a supercritical mixed solvent. The solubility of GF in supercritical CO2 with cosolvent acetone was measured using a dynamic apparatus at pressures between 120 and 320bar, temperatures at 313,323 and 333K and cosolvent concentration at 1.5, 3.0, 4.5 and 6.0 mol%. The effect of the pre-expansion pressure, the pre-expansion temperature, diameter of the nozzle, concentration of cosolvent and expansion chamber temperature on the precipitated particles was investigated. The results showed that the mean particle size of griseofulvin precipitated by RESS was less than 1.2 μ m . An increase in pre-expansion pressure, pre-expansion temperature, concentration of cosolvent resulted in decrease in particle size with the range of operating condition studied. With the decrease of nozzle diameter and pre-expansion temperature the particle size reduces. The crystallinity and melting point of the original material and the processed particle by RESS were tested by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). No evident modification in the crystal habit was founded at the experimental conditions tested. The morphology of particles precipitated was analyzed by scanning electron microscopy (SEM).