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The Pharmaceutical Society of Korea (대한약학회)
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Preparation and Characterization of Solid Dispersions of Itraconazole by using Aerosol Solvent Extraction System for Improvement in Drug Solubility and Bioavailability

  • Lee, Si-Beum (National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University) ;
  • Nam, Kyung-Wan (National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University) ;
  • Kim, Min-Soo (National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University) ;
  • Jun, Seoung-Wook (National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University) ;
  • Park, Jeong-Sook (National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University) ;
  • Woo, Jong-Soo (National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University) ;
  • Hwang, Sung-Joo (National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University)
  • Published : 2005.07.01
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Abstract

The objective of this study was to elucidate the feasibility to improve the solubility and bioavailability of poorly water-soluble itraconazole via solid dispersions by using supercritical fluid (SCF). Solid dispersions of itraconazole with hydrophilic polymer, HPMC 2910, were prepared by the aerosol solvent extraction system (ASES) under different process conditions of temperature/pressure. The particle size of solid dispersions ranged from 100 to 500 nm. The equilibrium solubility increased with decrease (15 to 10 MPa) in pressure and increase (40 to $60^{\circ}C$) in temperature. The solid dispersions prepared at $60^{\circ}C$/15 MPa showed a slight increase in equilibrium solubility (approximately 27-fold increase) when compared to pure itraconazole, while those prepared at $60^{\circ}C$/10MPa showed approximately 610-fold increase and no endothermic peaks corresponding to pure itraconazole were observed, indicating that itraconazole might be molecularly dispersed in HPMC 2910 in the amorphous form. The amorphous state of itraconazole was confirmed by DSC/XRD data. The pharmacokinetic parameters of the ASES-processed solid dispersions, such as $T_{max},\;C_{max},\;and\;AUC_{0-24h}$ were almost similar to $Sporanox_{\circledR}$ capsule which shows high bioavailability. Hence, it was concluded that the ASES process could be a promising technique to reduce particle size and/or prepare amorphous solid dispersion of drugs in order to improve the solubility and bioavailability of poorly water-soluble drugs.

Keywords

References

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