Enhanced solubility and oral bioavailability of itraconazole by combining membrane emulsification and spray drying technique.
The objective of the present study was to enhance solubility and bioavailability of itraconazole by a combined use of membrane emulsification and spray drying solidification technique. A shirasu-porous-glass (SPG) membrane with a mean pore size of 2.5 μm was used to produce monodispersed microemulsions of itraconazole consisting of methylene chloride as the dispersed phase, a mixture of Transcutol HP and Span 20 as a stabilizer, and dextran as solid carrier dissolved in water as the continuous phase. The dispersed phase permeated through the SPG membrane into the continuous phase at an agitator speed of 150 rpm, a feed pressure of 15 kPa and a continuous phase temperature of 25°C and the resultant emulsion was solidified using spray-drying technique. Solid state characterizations of the solid emulsion showed that the crystal state of itraconazole in solid emulsion was converted from crystalline to amorphous form. The solid emulsion of itraconazole displayed a significant increase in the dissolution rate than that of pure itraconazole. Furthermore, the solid emulsion after oral administration gave about eight-fold higher AUC and about ten-fold higher C(max) in rats than pure itraconazole powder (p<0.05), indicating this formulation greatly improved the oral bioavailability of drug in rats. Thus, these results demonstrated that the SPG membrane emulsification system combined with spray-drying technique could be used as a promising technique to develop solid formulation of itraconazole with enhanced solubility and bioavailability.
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
Young Keun
YK
Choi
Bijay K
BK
Poudel
Nirmal
N
Marasini
Kwan Yeol
KY
Yang
Jeong Whan
JW
Kim
Jong Oh
JO
Kim
Han-Gon
HG
Choi
Chul Soon
CS
Yong
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003460:Crystallization; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D006601:Hexoses / Q000737:chemistry; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008752:Methylene Chloride / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013696:Temperature
D003911:Dextrans; D004337:Drug Carriers; D004655:Emulsions; D005026:Ethylene Glycols; D005079:Excipients; D006601:Hexoses; D017964:Itraconazole; D008752:Methylene Chloride; C014822:sorbitan monolaurate; C010111:carbitol