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

Abstract

Background: Itraconazole is a triazole derivative and possesses structural similarities to the azole group (imidazoles and triazoles). It is a broad spectrum fungistatic. It belongs to BCS class II category i.e. it has poor solubility and high permeability. Objective: Dissolution enhancement of poorly soluble itraconazole using purified neem gum as a natural carrier via binary dispersions and other methods was studied. Topical gel formulations of binary dispersions were 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 prepared by the solvent evaporation technique. Other mixtures were also prepared by kneading, cogrinding, physical mixing methods and evaluated further. Topical gel formulations were further developed and evaluated for antifungal activity (both in vitro and in vivo). Results: Equilibrium solubility studies of various mixtures indicated SD3 (1:3) as the optimum batch out 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. FTIR studies indicated no interaction of the drug to the polymer. DSC, SEM and XRD studies indicated a transition from crystalline to the amorphous state of the drug. SD3 batch showed remarkably improved dissolution 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 significantly higher than that in comparison to pure drug based gel (30% in 24 h). The increased area of zone of inhibition of SD3 based gel indicated better antifungal activity of the SD3 gel formulation. Further histopathology examination of skin specimens indicated enhanced efficacy of SD3 based gel in comparison to pure drug based gel. Conclusion: Solid dispersion based topical gel formulation exhibits better antifungal activity in comparison to pure drug based gel.