Investigating effect of microemulsion components: In vitro permeation of ketoconazole.
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/cm(2)/h(1) 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.
Indukaka Ipcowala College of Pharmacy, Vallabh Vidyanagar, India. rashmru@gmail.com
Mrunali R
MR
Patel
Rashmin B
RB
Patel
Jolly R
JR
Parikh
Ajay B
AB
Solanki
Bharat G
BG
Patel
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002176:Candida albicans / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D007654:Ketoconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009821:Oils / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*; D013501:Surface-Active Agents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000935:Antifungal Agents; D004655:Emulsions; D005079:Excipients; D009821:Oils; D013501:Surface-Active Agents; D014867:Water; D007654:Ketoconazole