Preparation and characterization of solid dispersions of itraconazole by using aerosol solvent extraction system for improvement in drug solubility and bioavailability.
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 degrees C) in temperature. The solid dispersions prepared at 45 degrees C/15 MPa showed a slight increase in equilibrium solubility (approximately 27-fold increase) when compared to pure itraconazole, while those prepared at 60 degrees C/10 MPa 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 Tmax, Cmax, and AUC(o-24 h) were almost similar to Sporanox 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.
Lee
Sibeum
S
National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.
Nam
Kyungwan
K
Kim
Min Soo
MS
Jun
Seoung Wook
SW
Park
Jeong-Sook
JS
Woo
Jong Soo
JS
Hwang
Sung-Joo
SJ
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D045703:Emulsifying Agents / Q000737:chemistry; D065347:Hypromellose Derivatives; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014961:X-Ray Diffraction
D045703:Emulsifying Agents; D017964:Itraconazole; D065347:Hypromellose Derivatives; D008747:Methylcellulose