Sci. Pharm. 2009; 77: 401–417
Synergistic Enhancement of Itraconazole Dissolution by Ternary System Formation with Pluronic F68 and Hydroxypropylmethylcellulose
Gamal M. EL MAGHRABY * 1,2, Abdullah H. ALOMRANI 1
1 Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia.
2 Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt.
* Corresponding author. E-mail: gmmelmag@yahoo.com (G. M. El Maghraby).
Abstract
Pluronic F68 is a surfactant which can inhibit CYP3A4, an enzyme responsible for hepatic metabolism of many drugs including itraconazole. This study investigated the effect of incorporation of Pluronic F68 as a ternary component in solid dispersions of itraconazole with hydroxypropyl-methylcellulose (HPMC) on the dissolution rate of itraconazole. Binary solid dispersions with HPMC, reduced the drug crystallinity, increased the equilibrium solubility but showed slow dissolution. Binary dispersions with Pluronic produced eutectic systems but the increase in solubility and dissolution was lower than that of HPMC systems. Ternary system comprising optimum proportions of drug with Pluronic and HPMC enhanced the dissolution rate showing dissolution efficiency comparable to that obtained with the marketed product of itraconazole. The study thus presented a system capable of increasing the dissolution rate of itraconazole with a potential for increased oral bioavailability by inhibiting its pre-systemic metabolism as well.
Keywords
Itraconazole dissolution • Ternary solid dispersion • HPMC • Pluronic F68
Received January 6th, 2009 | Accepted March 2nd, 2009 | Published Online March 6th, 2009
