Influence of Fatty Acid-Alcohol Esters on Percutaneous Absorption of Hydrocortisone Butyrate Propionate

抄録

Transcutaneous drug absorption is influenced by the physicochemical properties of both the drug and the vehicle. The effect of the vehicle is very important for the maximum drug effect. The effect of the vehicle can be considered from two standpoints, drug release and interaction with the skin, and therefore absorption of the vehicle itself may affect drug absorption. Because of the wide variety of vehicles mixed in ointments, it is difficult to measure the percutaneous absorption of all of them. It is important to study the relationship between the physicochemical properties of vehicles and the enhancement of absorption of the drug.In this experiment, a series of fatty acid-alcohol esters have been selected since they are frequently used as vehicles for drugs and cosmetics. The effects of the physicochemical properties of these vehicles on the percutaneous absorption of hydrocortisone butyrate propionate (HBP), a topical antiinflammatory corticosteroid, were examined. The partition coefficients (log P) of vehicles were determined by calculation.The gel vehicle was applied to the abdominal skin of anesthetized rats. The skin was excised after an appropriate interval and drug absorption was calculated from the unabsorbed drug amount. Drug absorption was enhanced by several additives. The physicochemical property values of additives that may result in maximum drug absorptions were calculated. The optimum values were approximately 12 for the partition coefficient and about 400 for molecular weight. Additives that have quite high hydrophobicity were found to be suitable for HBP (log P=3.3). When isopropyl myristate was used as an additive, after about 15h the absorption rate of HBP was found to have increased. It was suggested that isopropyl myristate has a direct effect on the barrier function. The physicochemical properties of the absorption enhancer affect not only the release of the drug from the vehicle to the skin, but also the interaction between the vehicle and the skin after penetration into the skin.