Formulation and development of thermosensitive cyclodextrin-based in situ gel of voriconazole for vaginal delivery

Abstract

The aim of the study was to develop a vaginal in situ gel of Voriconazole (VZ). Considering the low aqueous solubility of VZ, hydroxyl propyl-beta-cyclodextrin based inclusion complex of VZ was prepared by spray drying at VZ: HP-β-CD molar ratio of 1:2.5. An in situ gelling formulations, with Poloxamer 407 (P 407) and Poloxamer 188 (P188), were prepared using drug inclusion complex. The effect of various mucoadhesive polymers on in situ gelling formulations was studied. The formulations were evaluated for gelling temperature, gelling ability, viscosity, mucoadhesion, drug content, in vitro drug release and in vivo vaginal tissue uptake in female wistar rats. The formulation with 18% P407, 5% P 188 and 0.4% HPMC was optimized and demonstrated excellent gelling ability, gelling temperature at 31.7 ± 0.1 °C, shear thinning behaviour, excellent mucoadhesion, 96.21 ± 1.16% drug content and 56.2 ± 0.44% of drug release in 8 h by fickian diffusion mechanism. In vivo vaginal tissue uptake study revealed higher drug uptake in vaginal tissue by optimized formulation than in situ gel without HP-β-CD and VZ dispersion administered intravaginally. The study revealed the potential of HP-β-CD based thermosensitive gel for vaginal delivery of VZ with higher tissue uptake.