Investigating effect of microemulsion components: In vitro permeation of ketoconazole

Abstract

The purpose of this study was to evaluate the effect of oil, surfactant/co-surfactant mixing ratios and water on the in vitro permeation of ketoconazole (KTZ) applied in O/W microemulsion vehicle through intact rat skin. Lauryl Alcohol (LA) was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulsion system. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the oil, Labrasol (Lab) as the surfactant (S) and ethanol (EtOH) as the cosurfactant (CoS). The formulation which showed a highest permeation rate of 54.65 ± 1.72 µg/cm²/h¹ and appropriate physico-chemical properties was optimized as containing 2% KTZ, 10% LA, 20% Lab/EtOH (1:1) and 68% double distilled water (w/w). The efficiency of microemulsion formulation in the topical delivery of KTZ was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio. It was concluded that the percutaneous absorption of KTZ from microemulsions was enhanced with increasing the LA and water contents, and with decreasing the Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved, which showed the widest zone of inhibition as compared to KTZ reference. The studied microemulsion formulation showed a good stability for a period of three months. Histopathological investigation of rat skin revealed the safety of microemulsion formulations for topical use. These results indicate that the studied microemulsion formulation might be a promising vehicle for topical delivery of KTZ.

Keywords::

• Antifungal activity
• in vitro skin permeation study
• microemulsion
• ketoconazole
• topical delivery

Acknowledgements

The authors are thankful to Alembic Ltd (Vadodara, India) for providing gratis sample of KTZ and facility for particle size analysis; Food and Drug Laboratory (Vadodara, India) for providing gratis sample of Candida albicans (ATCC 10231); Colorcon (Asia) Pvt. Ltd (Mumbai, India) for providing Labrasol; the Department of Bioscience, Sardar Patel University, for providing facilities to carry out antifungal activity; and the Department of Pharmacology, A. R. College of Pharmacy and G. H. Patel Institute of Pharmacy for providing rat skins; and Sophisticated Instrumentation Center for Advanced Research and Technology (SICART) (Vallabh Vidyanagar, India) for providing facilities for carrying out analytical work.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.