Solubility and micronization of griseofulvin in supercritical CHF3

Abstract

Griseofulvin (GF) is a n antimicotic compound whose pharmaceutical activity can be improved by particle size reduction. Its micronization was obtained by rapid expansion from 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 "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 I312 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 "C) and at different expansion chamber temperatures (from 10 to 25 "C). Two different morphologies of GF crystals were observed: quasispherical particles and needles. The process parameter controlling the transition from one morphology t o 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.

Solubility of Diflunisal in Supercritical Carbon Dioxide

“…Moreover, and mainly for this reason, a different strategy which considers the sublimation pressure as an adjustable parameter, together with the binary interaction parameters, can also be employed. 26,35,36 In this work, the employed values of diflunisal sublimation pressure were obtained based on diflunisal experimental sublimation pressure data, and this fact can explain the observed good fitting results achieved even with the one adjustable parameter model (PR-vdW1). Once again, this evidences the importance of having reasonably accurate sublimation pressure values when using these types of EOS models for the correlation of solid solubility experimental data.…”

Supercritical assisted atomization: A novel technology for microparticles preparation of an asthma-controlling drug

“…where ρ is the sample density expressed as g/cm 3 ; χ is the dynamic shape factor; d wg is the mean particle diameter.…”

“…For this reason, MMADs of drug particles were calculated from Equation 1 (see Methods section) to perform a more adequate comparison between the particles produced by SAA and commercial jet-milling. The particle density was evaluated by a pycnometer (see Methods section), and the measured mean density is of 1.2 g/cm 3 for SAA micronized particles, while the jet-milled sample shows a density of 1.4 g/cm 3 . A shape factor equal to 1 was assumed for the SAA particles and a shape factor of 1.2 was used for the commercial drug sample.…”

“…The most studied SF-based micronization techniques are the following: (1) the rapid expansion of supercritical solutions (RESS) 2,3 ; (2) the particles generation from gas saturated solutions (PGSS) 4,5 ; (3) the supercritical antisolvent precipitation (SAS) [6][7][8][9] ; and the supercritical carbon dioxide assisted nebulization (CAN-BD). 10,11 Supercritical fluids assisted atomization (SAA) is a process recently developed by our research group and proposed in this field.…”

Particle Design Using Supercritical Fluids

“…Therefore, we selected the starting operating conditions considering only the binary system VLE and assumed that the presence of the solute does not modify the miscibility behavior of the solvent/ CO 2 system or only produces a slight modification of the boundaries of the miscibility region. According to these considerations, the saturator operating conditions were set in dependence of the liquid solvent used and in the ranges of 90±120 bar and 70±90 C, trying to assure a large solubility of CO 2 between CO 2 and liquid solution was regulated to assure a moderate excess of CO 2 in the solvent. The range selected falls between 0.7 and 1.8 w/w.…”