Griseofulvin micronization and dissolution rate improvement by supercritical assisted atomization.
Supercritical assisted atomization (SAA) was used to micronize griseofulvin (GF), selected as a model compound, to verify the performance of this innovative process. SAA is based on the solubilization of supercritical carbon dioxide in a liquid solution containing the drug. The ternary mixture is then sprayed through a nozzle and microparticles are formed as a consequence of the enhanced atomization. Precipitation temperature and drug concentration in the liquid solution were studied to evaluate their influence on morphology and size of precipitated particles. A good particle size control was obtained and GF spherical particles with mean diameters ranging from 0.5 to 2.5 microm were produced with a narrow particle size distribution. Processed GF was characterized by high-performance liquid chromatography-UV/vis, headspace-gas chromatography-flame ionization detection, differential scanning calorimetry, BET and X-ray analyses. No drug degradation was observed and a solvent residue (acetone) less than 800 ppm was measured. GF microparticles showed good stability and surface areas ranging from about 4 to 6 m(2) g(-1); moreover, the micronized drug retained the crystalline habit. GF capsules were formulated with starch and used to compare the dissolution rate of SAA-processed and conventional jet-milled drug. A faster dissolution and a better reproducibility of the dissolution profile were observed for SAA-processed GF.
Reverchon
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Dipartimento di Ingegneria Chimica e Alimentare, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy. ereverchon@unisat.it
Della Porta
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G
Spada
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A
Antonacci
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A
D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D006118:Griseofulvin / Q000008:administration & dosage* / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D012995:Solubility; D012997:Solvents; D013696:Temperature
D000935:Antifungal Agents; D012997:Solvents; D006118:Griseofulvin