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The modelling of skin absorption and controlled drug delivery to the skin.
Hadgraft J; Guy RH
Controlled Drug Delivery: International Symposium of the Association for Pharmaceutical Technology (APV), Bad Homburg, 12-14 November, 1984. Muller BW, ed., Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH, 1987 Jan; :238-249
The pharmacokinetics of the controlled delivery of drugs to the skin for local application and systemic therapy were reviewed in relation to the modelling of skin drug absorption. The percutaneous absorption of drugs across the stratum corneum was considered in terms of Fick's diffusion equations and the physiochemical properties of the skin as described by first order rate constants. Modelling based on Fick's laws of diffusion included mathematical analysis of the diffusion of the drug through the delivery system, partitioning of the drug into the skin and diffusion through the stratum corneum, the partitioning and diffusion of the drug within the viable epidermis, and removal of the drug by the cutaneous blood supply. Such modelling was used to test nicotinic esters as potential penetrants than enter the skin relatively quickly to produce dilation of the capillaries at the dermal epidermal junction. Pharmacokinetic modelling incorporated four rate constants: k1, k2, k3, and k4. The rate constant k1 described the diffusion of the drug across the stratum corneum and was related to molecular weight of the drug and the Stokes Einstein equation, and k2 described the diffusion across the viable epidermis in similar manner. The constant k3 was a partition coefficient that described the relative affinity of the drug to the stratum corneum and the viable epidermis and was linearly related to the octanol water partition coefficient. The systemic elimination of the drug from the blood was described by k4. Knowledge of the physiochemical properties of a drug and pharmacokinetic modelling permitted prediction of delivery kinetics for both topical applications and different transdermal delivery devices.
NIOSH-Grant; Dermatitis; Drug-therapy; Medical-treatment; Analytical-models; Pharmacodynamics; Skin-sensitivity; Therapeutic-agents; Biokinetics
Pharmacy University of California 926 Medical Sciences Building San Francisco, Calif 94143
Controlled Drug Delivery: International Symposium of the Association for Pharmaceutical Technology (APV), Bad Homburg, 12-14 November, 1984
University of California San Francisco, San Francisco, California
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