Development and evaluation of clotrimazole microemulsions for topical application: Effects of HLB value of surfactant mixture and cosurfactant type on formulation design

Clotrimazole is a synthetic imidazole with broad-spectrum antimycotic effect that has been widely used for the topical treatment for athlete's foot (tinea pedis), oropharyngeal and vulvovaginal candidiasis. The objective of the study was to develop a nano-delivery system containing to improve the penetration capacity of Clotrimazole. Microemulsions were formulated and the chemophysical properties, permeability through rat skin and irritancy examined by HET-CAM test of drug-loaded formulations and stability were evaluated. The average droplet size and viscosity of all clotrimazole-loaded microemulsion formulations were respectively between 126.7-228.13 nm with PDI value less than 0.31 and 24.53-155.16 mPa·s. The penetration capacity of clotrimazole was markedly improved by using microemulsion formulations as delivery carriers: the 24-h cumulative permeated amount from the optimized microemulsion was approximately three-fold higher than that from the clotrimazole solution (drug dissolved in 30 % ethanol) and about 6.5-fold higher than that from the commercial product. The HET-CAM test showed the irritancy on skin of designed clotrimazole-loaded formulation was acceptable compared to the positive control of 0.8 % paraformaldehyde aqueous solution. The stability studies showed that the physicochemical characteristics and residual drug percentage (about 95.3 %) of F2 clotrimazole-loaded formulation were fairly stable after thermodynamic and storage tests, indicating designed microemulsions as a delivery carrier could be considered as a potential strategy for clotrimazole topical dosage form deployment.