Improved Solubility of Itraconazole Binary Dispersions using Neem Gum: Development and Characterization of Topical Gel

摘要

Background: Itraconazole is a triazole derivative and possesses structural similarities to theazole group (imidazoles and triazoles). It is a broad spectrum fungistatic. It belongs to BCS class IIcategory i.e. it has poor solubility and high permeability.Objective: Dissolution enhancement of poorly soluble itraconazole using purified neem gum as a naturalcarrier via binary dispersions and other methods was studied. Topical gel formulations of binary dispersionswere developed and evaluated for in vitro and in vivo antifungal activity.Methods: Five batches of solid dispersions (SD1-SD5) in various ratios of drug: neem gum were preparedby the solvent evaporation technique. Other mixtures were also prepared by kneading, cogrinding,physical mixing methods and evaluated further. Topical gel formulations were further developedand evaluated for antifungal activity (both in vitro and in vivo).Results: Equilibrium solubility studies of various mixtures indicated SD3 (1:3) as the optimum batchout of all solid dispersion batches. Equilibrium solubility studies of mixtures (KM, CGM, PM, SM)indicated significant solubility enhancement of kneading mixture in comparison to other mixtures. FTIRstudies indicated no interaction of the drug to the polymer. DSC, SEM and XRD studies indicated atransition from crystalline to the amorphous state of the drug. SD3 batch showed remarkably improveddissolution characteristics (100% drug release in 1.5 h) in comparison to the pure drug (38% in 2h).Further, the topical gel of SD3 was evaluated for in vitro diffusion, in vitro and in vivo antifungal activity.Sustained drug release (53% in 24 h) was observed in SD3 based gel formulation which is significantlyhigher than that in comparison to pure drug based gel (30% in 24 h). The increased area of zoneof inhibition of SD3 based gel indicated better antifungal activity of the SD3 gel formulation. Furtherhistopathology examination of skin specimens indicated enhanced efficacy of SD3 based gel in comparisonto pure drug based gel.Conclusion: Solid dispersion based topical gel formulation exhibits better antifungal activity in comparisonto pure drug based gel.