Clotrimazole mucoadhesive films with extended-release properties for vaginal candidiasis-A hot-melt extrusion application.

Abstract

Clotrimazole, an antifungal agent for treating vaginal candidiasis, faces challenges in localized delivery due to poor solubility, complexity of the vaginal environment, limited fluid for dissolution, and rapid self washout of the vagina. The study aimed to enhance clotrimazole solubility using hot-melt extrusion (HME) to develop vaginal films with adequate bioadhesion, mechanical strength, and extended-release properties. Different formulations were created by varying the ratios of polyethylene oxide (PEO) grades (N750 and N10) to adjust the films' properties. The films demonstrated extended-release profiles, prolonging clotrimazole release for up to eight hours, with a cumulative gradual and complete in- vitro release in 100 mL of simulated vaginal fluid with 0.5% sodium dodecyl sulfate. In contrast, the marketed vaginal ovules exhibited a rapid and complete release within 30 minutes of shell rupture. The release kinetics followed Krosmeyer-Peppas model, and zero-order release mechanism. Films containing 25% clotrimazole, 56.25% PEO N750, and 18.75% PEO N10 exhibited strength of 87.9 N, stiffness of 35 N/sec, and adhesive force of 3.85 N.mm. In conclusion, the novel clotrimazole-loaded vaginal films developed using HME technology enhanced the solubility and localized vaginal delivery of clotrimazole. The extended-release profile may reduce the dosing frequency, enhance patient adherence, and improve therapeutic outcomes.