Investigating effect of microemulsion components: In vitro permeation of ketoconazole

• Published in: Pharmaceutical development and technology 2011-06, Vol.16 (3), p.250-258
• Main Authors: Patel, Mrunali R., Patel, Rashmin B., Parikh, Jolly R., Solanki, Ajay B., Patel, Bharat G.
• Format: Article
• Language: English
• Subjects: Animals; Antifungal activity; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacokinetics; Candida albicans - drug effects; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Stability; Emulsions - chemistry; Excipients - chemistry; in vitro skin permeation study; ketoconazole; Ketoconazole - administration & dosage; Ketoconazole - pharmacokinetics; Male; microemulsion; Oils - chemistry; Rats; Rats, Wistar; Skin Absorption - drug effects; Surface-Active Agents - chemistry; topical delivery; Water - chemistry
• ISSN: 1083-7450; 1097-9867
• DOI: 10.3109/10837451003610845

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.