수종 용제와 투과 촉진제를 이용한 로바스타틴의 용해성 및 피부 투과 증진

Enhanced Solubility and In vitro Skin Permeation of Lovastatin Using Some Vehicles and Penetration Enhancers

To enhance the in vitro permeation of lovastatin through excised hairless mouse and human cadaver skins, sol- ubility was determined in various hydrophilic and lipophilic vehicles, and the effects of vehicles and penetration enhancers on the skin permeation from solution formulations were investigated. Solubility of lovastatin was highest in N-methyl-2-pyr-rolidone (NMP) (278.2±10.1 mg/ml) and dimethyl sulfoxide (DMSO) (162.2±9.7 mg/ml). Among different pure vehicles used, NMP, DMSO, propylene glycol and isopropyl myristate provided some drug permeation (6.9±1.1, 5.9±1.6, 3.0±0.5 and 2.2±0.3 μg/cm2 at 24 hr, respectively) through hairless mouse skin. The addition of oleic acid, linoleic acid and oleyl alcohol to DMSO showed the maximum permeation at around 5 v/v%, however, capric acid and caprylic acid had no enhanc-ing effect. The increase of enhancer concentrations showed bell-shaped permeation rate, suggesting the presence of optimal concentration in lovastatin penetration. Increasing donor concentration from 10 mg/ml to 80 mg/ml in DMSO and a cosol-vent of DMSO, NMP and DGME (3 : 3 : 4 v/v) did not show significant dose dependent permeation in both hairless mouse and human cadaver skins. The maximum lovastatin flux through human cadaver skin was found to be 0.87±0.46 μg/cm2/hr with 5 v/v% linoleic acid and donor dose of 4 mg/0.64 cm 2 in the cosolvent. These results suggest that transdermal deliv-ery of lovastatin would be feasible by establishing the optimal concentrations of donor dose and unsaturated fatty acids in appropriate vehicles.