Abstract: Griseofulvin (GF) is an antifungal drug whose pharmaceutical activity can be improved by
reducingparticle size. In this study the rapid expansion of supercritical solution (RESS)
was employed to micronize GF.Carbon dioxide with cosolvent acetone was chosen as a
supercritical mixed solvent. The solubility of GF in super-critical CO2 with cosolvent
acetone was measured using a dynamic apparatus at pressures between 12 and 32
MPa,temperatures at 313, 323 and 333K and cosolvent concentration at 1.5, 3.0, 4.5 and 6.0%
(by mole). The effect ofpre-expansion pressure, extraction temperature, spraying distance,
nozzle size and concentration of cosolvent on theprecipitated particles was investigated.
The results show that the mean particle size of griseofulvin precipitated byRESS was less
than 1.2 μm. An increase in pre-expansion pressure, extraction temperature, spraying
distance andconcentration of cosolvent resulted in a decrease in particle size under the
operating condition studied. With thedecrease of nozzle diameter the particle size reduces.
The crystallinity and melting point of the original material andthe processed particle by
RESS were tested by X-ray diffraction (XRD) and differential scanning calorimetry (DSC).No
evident modification in the crystal habit was found under the experimental conditions
tested. The morphologyof particles precipitated was analyzed by scanning electron
microscopy (SEM).

Key words: griseofulvin, micronization, RESS process, cosolvent

摘要：

Griseofulvin (GF) is an antifungal drug whose pharmaceutical activity can be improved by
reducingparticle size. In this study the rapid expansion of supercritical solution (RESS)
was employed to micronize GF.Carbon dioxide with cosolvent acetone was chosen as a
supercritical mixed solvent. The solubility of GF in super-critical CO2 with cosolvent
acetone was measured using a dynamic apparatus at pressures between 12 and 32
MPa,temperatures at 313, 323 and 333K and cosolvent concentration at 1.5, 3.0, 4.5 and 6.0%
(by mole). The effect ofpre-expansion pressure, extraction temperature, spraying distance,
nozzle size and concentration of cosolvent on theprecipitated particles was investigated.
The results show that the mean particle size of griseofulvin precipitated byRESS was less
than 1.2 μm. An increase in pre-expansion pressure, extraction temperature, spraying
distance andconcentration of cosolvent resulted in a decrease in particle size under the
operating condition studied. With thedecrease of nozzle diameter the particle size reduces.
The crystallinity and melting point of the original material andthe processed particle by
RESS were tested by X-ray diffraction (XRD) and differential scanning calorimetry (DSC).No
evident modification in the crystal habit was found under the experimental conditions
tested. The morphologyof particles precipitated was analyzed by scanning electron
microscopy (SEM).

关键词: griseofulvin;micronization;RESS process;cosolvent