Predictive Skin Permeation of Ethinylestradiol, α-Asarone, Finasteride and Risperidone

OBJECTIVE To predict drug skin permeability by using QSPR models, and verify the applicability and veracity of the models for skin percutaneous penetration.METHODS Four drugs:ethinylestradiol, α-asarone,finasteride and risperidone were employed as model drugs, and Potts-Guy, Cronin,Moss, Morimoto, Kitagawa, Magnusson and Lien-Gao equations were selected as QSPR models. Combined drug physical-chemical parameters with QSPR models, the skin percutaneous data were calculated. The penetration experiments in vitro were also carried out on modified Franz-Diffusion Cells, using aqueous drug solutions at saturate solubility, through excised human skin. Samples were withdrawn from the receptor phase at specified time points and the concentrations were determined by HLPC, the maximum steady penetration rates were calculated. Comparing the predictive datas with experimental ones, the most appropriate model was determined. RESULTS The log Jmax for four drugs were superimposed with the 95%CI predicted by the related seven models. It is of statistic meaning. Models utilizing descriptors of hydrophobicity and molecular weight have better prediction,according to RMSE, the accuracy of models follows as Potts-Guy>Cronin>Kitagawa,Morimoto>Magnusson>Moss,Lien-Gao.CONCLUSION QSPR models can well predict skin penetration, and Potts-Guy model has the best prediction ability.