Industrial & Engineering Chemistry Research, Vol.34, No.11, 4087-4091, 1995
Solubility and Micronization of Griseofulvin in Supercritical Chf3
Griseofulvin (GF) is an antimicotic compound whose pharmaceutical activity can be improved by particle size reduction. Its micronization was obtained by rapid expansion fi om a supercritical solution (RESS). Trifluoromethane (CHF3) was chosen as a supercritical solvent and the Bender equation of state was selected to represent its volumetric properties. GF solubility in supercritical CHF3 was studied at temperatures of 40 and 60 degrees C and in the pressure range from 120 to 330 bar. The solubility data was fitted by using the Peng-Robinson (PR) equation of state in which the sublimation pressure of CHF3 and the k(12) interaction parameter were considered as adjustable parameters. RESS experiments were performed at different preexpansion pressures (from 180 to 220 bar) and temperatures (from 60 to 150 degrees C) and at different expansion chamber temperatures (from 10 to 25 degrees C). Two different morphologies of GF crystals were observed : quasispherical particles and needles. The process parameter controlling the transition from one morphology to the other was the preexpansion chamber temperature. The orientation and the coalescence of GF crystals was also sometimes observed. Our hypothesis was that this could be due to the presence of electrostatic charges induced by the fast motion in the expansion chamber and located on the surface of the GF particles.