Optimisation of clotrimazole emulgel using essential oils of Citrus sinensis and Zingiber officinale as permeation enhancers

Background: Current trends in emugel formulations are devoid of utilization of natural permeation enhancers which will increase the amount of clotrimazole that is available at the site of infection for treatment of vaginal candidiasis. Objective: The aim of this study is to develop clotrimazole emulgel using Carbopol® Ultrez 21 and Carbopol 940® and two natural permeation enhancers essential oils from the peel of Citrus sinensis and Zingiber officinale. Method: Eight clotrimazole emulgel formulations were prepared according to a 2 3 factorial design using qualitative factors and levels such as gelling agent type, natural permeation enhancers concentrations and emulsifying agent concentration. The formulated emugels underwent rheological evaluation, spreading coefficient, bioadhesive strength measurement. Release kinetics, microbiological assay and stability of the formulations were studied. In vivo release studies using cellulose based Ciprophan®membrane and ex vivo via rat skin permeation studies were carried out to evaluate the impact of the essential oils on the release of clotrimazole. Results: The increase in polymer concentration from 1% to 2% led to a corresponding increase in viscosity and spreadability of the emugel formulation. Hixon Crowell model best because it had correlation coefficient of 0.8464 – 0.9259 through membrane and 0.9245-0.9652 through rat skin. Correlation coefficient ranging from 0.9924 to 0.9992 means an excellent model fit. Conclusion: Utilization of Zingiber officinale essential oil in the emugel formulation at 3% w/w while eliciting synergistic antifungal activity with clotimazole, gave an enhanced release of clotimazole in vivo and ex vivo with flux 131.21±0.19 mg/cm 2 /h and 22.01±0.66mg/cm 2 /h respectively compared to the innovator brand 89.63±0.12 mg/cm 2 /h and 13.99±0.16mg/cm 2 /h respectively.