Development of an itraconazole-loaded gelatin microcapsule with enhanced oral bioavailability: physicochemical characterization and in-vivo evaluation.
OBJECTIVE
The aim of this study was to develop a novel itraconazole-loaded gelatin microcapsule without ethanol with enhanced oral bioavailability.


METHODS
Various gelatin microcapsules were prepared using a spray-drying technique. Their physicochemical properties, dissolution, characteristics and pharmacokinetics in rats were evaluated and compared with those of a commercial product.


RESULTS
The gelatin microcapsule at a weight ratio for itraconazole/gelatin/citric acid of 1 : 3 : 0.3 was spherical in shape with a smooth surface and inner hole, and gave a maximum drug solubility of about 700 microg/ml. The gelatin microcapsule dramatically increased the initial dissolution rate of itraconazole compared with a commercial product in simulated gastric fluids (pH 1.2). Moreover, at the same dose as the commercial product, it gave significantly higher initial plasma concentrations, C(max) and AUC of itraconazole in rats than did the commercial product, indicating that providing the drug in the gelatin microcapsule caused enhanced absorption in rats. At half dose, it gave similar AUC, C(max) and T(max) values to the commercial product, suggesting that it was bioequivalent to the commercial product in rats.


CONCLUSIONS
The itraconazole-loaded gelatin microcapsule without ethanol developed using a spray-drying technique at half the dose of the commercial product can deliver itraconazole in a pattern that allows fast absorption in the initial phase, making it bioequivalent to the commercial product.
Li
Dong Xun
DX
College of Pharmacy, Yeungnam University, Dae-Dong, Gyongsan, South Korea.
Park
Young-Joon
YJ
Oh
Dong Hoon
DH
Joe
Kwan Hyung
KH
Lee
Jung Hoon
JH
Yeo
Woo Hyun
WH
Yong
Chul Soon
CS
Choi
Han-Gon
HG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019343:Citric Acid; D004337:Drug Carriers / Q000737:chemistry*; D005750:Gastric Juice; D005780:Gelatin; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D017964:Itraconazole / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
D002214:Capsules; D004337:Drug Carriers; D019343:Citric Acid; D017964:Itraconazole; D005780:Gelatin