Influence of different layers of skin on the percutaneous absorption of drugs with different lipophilicity

OBJECTIVE: The purpose of this study was to evaluate the barrier function of different skin layers on the percutaneous penetration of model drugs. METHODS: 6 kinds of drugs (5-fluorouracil, theophylline, hydroquinone, barbital, isosorbide dinitrate and ketoprofen) with a wide span of lipophilicity were chosen and their in vitro permeability via intact skin or stripped skin was investigated in the patch dosage forms. RESULTS: There were characteristic parabolic relationship between the Permeability (Kp cm&middot h-1) of the drugs with different lipophilicity and their Log Pceither via intact skin or stripped skin. However, due to stratum corneum stripped, the increased Kp ratio for test drugs was mainly proportional to their solubility in water. When absorption promoter IPM (isopropyl myristate) was co-administered with the drugs, the parabolic relationship no longer existed. For the intact skin, the enhanced Kp ratio of 6 drugs resulting from IPM rose up when drug's Log Pc decreased. On the other hand, in the case of stripped skin, this enhancement ratio of Kp due to addition of IPM was related to drug's solubility in IPM, which meant that the enhanced Kp ratio had a gradual rising tendency as drug's solubility in IPM became larger. CONCLUSION: These data and methods represented a novel approach to evaluate the effects of skin damage and skin disease on drug percutaneous absorption.