Temperature-dependent in Situ Gel of Clotrimazole: an Experimental Study

Abstract

Abstract Background: The in-situ gel-forming polymeric formulations offer sustained and prolonged action in comparison to conventional drug delivery systems. Aim: To formulate and evaluate in situ vaginal gel of clotrimazole. Materials and methods: Poloxamer 407 (20%) was slowly added to freezing water (5°C) with constant stirring. The prepared dispersion was refrigerated for 5 h, the different concentrations of polymers were added for preliminary batches. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were performed for clotrimazole-excipients compatibility study. The final batch was prepared and evaluated for physicochemical parameters, in vitro clotrimazole release, in vitro antifungal activity, and in vivo vaginal tissue irritation test. Results: The compatibility study showed no chemical interaction between clotrimazole and excipients used. The evaluation parameters showed that clotrimazole release was in the range of 8 to 10 h, gelling temperature was in the range of 27–35°C, gelling time was in the range of 28–34 sec, pH was in the range of 4.4–4.8, and viscosities were in the range of 16.4–182.6 cP (solution form) and 10,500–20,756 cP (gel form). The zone of inhibitions for clotrimazole pure drug, the marketed vaginal gel of clotrimazole, and optimized gel formulation was 9.15±0.75 mm, 14.35±1.12 mm, and 18.85±1.56 mm, respectively (p < 0.0001, q = 5.98). An optimized gel formulation was not irritant to vaginal tissue. Conclusion: It was possible to formulate effective in situ vaginal gel for control release action of clotrimazole. Level of Evidence: IIC.