PREPARATION AND EVALUATION OF TERNARY MIXING ITRACONAZOLE SOLID DISPERSIONS BY SPRAY DRYING METHOD S.Rajarajan,

The present study aims to experiment the solid dispersion of poorly water soluble drug itraconazole as model drug by spray drying method with the use of PEG/HPMC polymer blends, the influence of polymer compatibility on the degree of molecular dispersion of itraconazole solid dispersions are prepared by ternary mixing and polymer blends are also evaluated for DSC, XRD and in vitro dissolution testing. Thermal analysis of DSC and XRD graphs were analysed to evaluate the status of glass transition state ternary solid dispersion phases. Among the formulations with 15/85 (w/w) PEG/HPMC ratio was found better amorphous nature in relation with invitro release. Introduction The current status of scientific development also get highly variable oral bioavailability of drugs due to low solubility and or dissolution rate in the gastrointestinal absorption of many new drugs. Even though there are many methods intended to solve the problem in which the formulation of solid dispersion is one of the ideal methods to experiment. The solid dispersions as a dispersion of one or more active ingredients in an inert carrier or matrix, prepared by the melting, solvent, or melting solvent method [1]. The increase in dissolution rate and solubility provided by solid dispersions can be explained by the mechanisms described by the Noyes–whitney equation [2]. A significant particle size reduction can be obtained by manufacturing solid dispersions and in many cases the drug is molecularly dispersed in the carrier. Conversion of the physicochemical state of the drug, e.g. from crystalline to amorphous, as well as solubilization and supersaturation by the carrier, can cause an increase in the kinetic solubility and the dissolution rate [3]. Itraconazole is a potent synthetic triazole antifungal drug with activities against broad spectrum of fungal species [4,5]. It has a molecular formula C35H38Cl2N8O4, molecular weight of 705.64, and is a weak basic drug, possessing extremely low water solubility (S~1 ng/ml at neutral pH and S~ 6ng/ml at pH 1), and pKa of 3.7 [6]. The mechanism of action of this compound is similar to all other azole antifungals. It inhibits cytochrome P450 of the fungi and thus interferes in sterol biosynthesis in cell membrane, leading to cell death [7]. According to the biopharmaceutics classification system, itraconazole is an extreme example of a class II compound meaning that its oral bioavailability is determined by dissolution rate in the GI tract [8,9,10]. Although the use of solid disperse technique for solubility enhancement of itraconazole has been reported by several authors [11], there are only two main methods for the solid dispersion preparation: solvent casting and melt extrusion. Solid state transformations of the crystalline drug to polymorphic modifications or to the amorphous state might lead to an increase in Correspondence