Design and Development of Clotrimazole Film for the Treatment of Vaginal Candidiasis

Abstract

The aim of present investigation was design and development of vaginal mucoadhesive vaginal film containing clotrimazole for the treatment of vaginal candidiasis which can be retained in vagina for prolonged period of time. Clotrimazole is an imidazole derivative mainly used in the treatment of vaginal candidiasis. To overcome the problem associated with conventional dosage form, mucoadhesive vaginal film was formulated by solvent casting method. Sodium alginate and chitosan were used as film forming agent. Combination of polymers was used to improve mechanical property of film and provide controlled release. Polyelectrolyte complex was formed between sodium alginate (anionic) and chitosan (cationic) as both the polymers have opposite charge in nature. Both the polymers are biodegradable, non-toxic and have good bioadhesion property. Glycerin was added as a plasticizer to enhance mechanical property such as tensile strength, % elongation, folding endurance. Drug-excipient compatibility study was carried out using Fourier transfer infrared spectroscopy and Differential scanning calorimeter. Isopropyl myristate was selected as a permeation enhancer. DOE helps to identify the region for obtaining desired values. The variations in independent variables assures acceptable values of dependent variables. Optimization of batch was done by Box-Behnken design. Effect of drug: polymer ratio, plasticizer ratio and concentration of IPM was considered as an independent variables and tensile strength, % elongation, % swelling and % diffusion were considered as a dependent variables. Vaginal film was evaluated for various mechanical and physical parameters such as tensile strength, % elongation, % swelling index, folding endurance, drug content and in-vitro diffusion study. Optimized batch shows 68.13% drug diffusion (Q8), 0.986±1.58 N/mm2 tensile strength, 3.83±0.46% elongation and 29.05±0.46% swelling index. Optimized formulation was compared with marketed Candid® gel to check in-vitro anti-fungal activity and in-vivo irritation study.