Optimization of Topical Therapy: Partitioning of Drugs into Stratum Corneum |
| |
Authors: | Surber Christian Wilhelm Klaus-P. Hori Mitsuhiko Maibach Howard I. Guy Richard H. |
| |
Affiliation: | (1) Department of Dermatology, School of Medicine, University of California at San Francisco, San Francisco, California, 94143;(2) Department of Dermatology, School of Medicine, University of Basel, CH-4031 Basel, Switzerland;(3) School of Pharmacy, UCSF, San Francisco, California, 94143-0446 |
| |
Abstract: | To optimize a topical formulation for therapeutic effect generally implies that the flux of drug into the skin be maximized. This requirement means that the product of drug concentration in the vehicle (Cv) and drug partition coefficient (PC) between stratum corneum (SC) and vehicle be as large as possible. While Cv is a formulation variable which can be easily manipulated up to the drug's saturation solubility, PC is a parameter that is difficult to predict a priori. However, there is no question that an ability to evaluate PC would greatly facilitate the efficient screening of drugs and formulations. We have measured the SC/water and SC/isopropylmyristate (a model lipophilic vehicle) PCs of seven drugs: acitretin, progesterone, testosterone, diazepam, estradiol, hydrocortisone, and caffeine. SC/ water PCs were determined as a function of the following variables: (i) initial drug concentration in the vehicle, (ii) length of equilibrium, (iii) SC source and preparation technique, and (iv) SC delipidization. The data obtained were reproducible and physicochemically consistent, and they show that useful partitioning information from both aqueous and nonaqueous vehicles can be obtained with the biological tissue of greatest relevance. The SC/water PCs of the steroids were in reasonable agreement with previous measurements. A facile approach to an integral determinant of formulation optimization is suggested, therefore, by these observations. |
| |
Keywords: | partition coefficient steroids stratum corneum skin percutaneous absorption |
本文献已被 SpringerLink 等数据库收录! |
|