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

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.