TRANSDERMAL DELIVERY OF LEVONORGESTREL .10. EFFECT OF COSOLVENTS ON ETHYL-ACETATE ENHANCED PERCUTANEOUS-ABSORPTION OF LEVONORGESTREL

The effect of various cosolvents on ethyl acetate (EtAc) enhanced percutaneous absorption of levonorgestrel (LN) was studied using excised hairless mouse skin. The steady-state flux of LN through hairless mouse skin was increased when mixtures of EtAc and ethanol (EtOH) were used as donor phase solvents relative to that when neat EtAc was used. For example, the flux of LN was increased about 2 fold (4.5 to 10 μg/cm2 h) when EtOH was added to EtAc at a volume fraction of 0.5 relative to neat EtAc. In contrast, the flux of LN from water was measured at 0.02 μg/cm2 h. Adding oleic acid or isopropyi myristate at a volume fraction of 0.5 in EtAc lowered the flux to approximately 1.0 μg/cm2 h. In contrast, when oleic acid was added to EtAc/EtOH (1:1) or EtOH, both at a volume fraction of 0.05, the transdermal flux of LN was found to be 9 and 7 μg/cm2 h, respectively. Apparent diffusion coefficients and partition coefficients were calculated and it was found that EtAc and EtOH increased the diffusivity of LN relative to water while skin/vehicle partition coefficients correlated roughly with the observed flux of LN from the saturated solutions, with the exception of the water vehicle. © 1990.