Formulation and Evaluation of Microemulsion of Curcumin in Thymol-Menthol Carrier System

Aim: To formulate and evaluate the Micro emulsion of curcumin in thymol-menthol carrier system.

Study Design: Curcumin dissolves in mixture of thymol & menthol to reasonable extent.100 mg of curcumin in 1 g of thymol and 0.6 g of menthol mixture was finalized as product mixture. The solution of curcumin in eutectic mixture being oily liquid, it gave the idea for development for the micro emulsion

Place and Duration of Study: Department of Pharmaceutics and Department of Pharmacognosy, STES’s Smt. Kashibai Navale College of Pharmacy, Kondhwa (BK), National Chemical Laboratory, Pune between June 2016 and May 2017.

Methodology: Micro emulsion system with eutectic mixture of thymol and menthol was chosen as oil phase and carrier for curcumin, tween 80 as surfactant and ethanol as co-surfactant. Ternary phase diagrams were constructed to obtain the optimum concentration range of oil phase, surfactant and co-surfactant. The micro emulsion of 100 mg curcumin containing 4.95 % oil phase, 33.39 % surfactant, 11.13% co-surfactant, 50:50% of water was optimum. Micro emulsion of curcumin was prepared by water titration method and evaluated for globule size, drug content, pH, viscosity, conductivity and In vitro drug release study. The ex-vivo permeation study for micro emulsion of curcumin was carried out on excised mice skin using Franz Diffusion apparatus. The cytotoxicity study for thymol, menthol was performed on healthy L929 murine fibroblast cell line. Anticancer activity of thymol-menthol eutectic mixture alone and with curcumin was performed on HeLa cell lines.

Results: The preformulation studies did clearly indicate good compatibility of drug with thymol menthol carrier system. The cytotoxicity study was done on thymol – menthol(TM) as a preformulation aspect to ascertain the toxicity of these two excipients to be tried. It was found that TM was not cytotoxic in 120ug/mL concentration and thus was safe to be used in concentration below 120ug/mL. Batch B1 was optimised. The average globule size of micro emulsion was found to be 131.54 nm, zeta potential was found to be -0.57 mV. The drug content in micro emulsion batch B1 was determined and found to be 74.6%.Permeability study across mice skin ex-vivo model showed 52.38% permeability compared with curcumin alone which was 22.41%. So permeability of curcumin is enhanced substantially with micro emulsion made in thymol and menthol, owing to fact that thymol and menthol act as good permeation enhancers. The In vitro drug release study of micro emulsion was compared with curcumin alone. About 48.75% of curcumin was released from micro emulsion showed increase in release rate.

Conclusion: Eutectic mixture of thymol and menthol showed promising results as penetration and solubility enhancer for curcumin. Solubility of curcumin was improved so as its rate of permeation which was used to develop formulation of micro emulsion with proven anticancer activity. The solubility of curcumin formulated with combination of eutectic mixture was increased up to 50 %.