Chemico-pharmaceutical investigations of an inclusion complex formed with valacyclovir and γ-cyclodextrin optimized by molecular docking for innovative applications as topical gel

Abstract

Valacyclovir hydrochloride (VC) possesses more oral bioavailability among all the anti-herpes drugs and more effective performance than acyclovir. The goal of the current research was to synthesize and characterize the inclusion complex of VC (ICVC) with gamma-cyclodextrin (γ-CD) utilizing various spectroscopic and physicochemical techniques like UV-vis, ¹H-NMR, FTIR, conductance, surface tension, and SEM analysis. The studies confirmed that the 1 : 1 stoichiometry of the formed ICVC was well supported by molecular docking and DFT study. After complexation with γ-CD, the photostability was enhanced. The purpose of the current study was to create topical gels loaded with VC and ICVC and assess their potential to increase VC penetration through the topical route by enhancing their pharmacokinetic profile. The optimized topical gels containing VC and ICVC have zeta potentials of −3.8 ± 1.0 mV and −5.7 ± 0.9 mV, respectively. An in vitro drug release study showed that at the end of 8 h, 32.3% and 23.38% release of VC was observed from the VC-loaded and ICVC-loaded gel. An ex vivo skin permeation study of the ICVC-loaded gel showed poor permeability and negligible flux value in comparison to the VC-loaded gel, which implies the retainability of the drug at the dermal site as a depot formulation from which the drug will be released and act in a sustained manner. Based on these findings, it was confirmed that the efficacy of VC can be much improved through the topical delivery of ICVC-loaded gel for the treatment of herpes with minimum dose requirements, less toxicity, rapid action, and improved bioavailability of the VC.