The development of a model for percutaneous absorption

• Main Author: Hadgraft, Jonathan
• Published: University of Oxford 1976
• Subjects: 615.19
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.457712

A novel piece of diffusion apparatus has been developed which utilizes the well characterized hydrodynamics of a rotating disc. Liquid liquid interfaces may be established on either side of the filter in the cell and the rate at which species are transferred from one phase to the other can be measured. The rates are measured at different rotation speeds and by extrapolation to infinite rotation speed the rate constant for the transfer reaction at the interface can be obtained; These interfacial rate constants have been measured for some carboxylic acids and esters of nicotinic acid. The nicotinates have been chosen since their rate of skin penetration is easily measured. In order to study the rate of percutaneous absorption, solutions of the nicotinates are applied to the forearm. The material diffuses through the skin and when it reaches the blood vessels a red response develops. By timing the onset of the red response an estimate of the rate of penetration is obtained. Three nicotinates have been chosen to cover a wide range of partition coefficients. A mathematical model has been developed to describe the transport of drugs across skin. This has been combined with the in vivo measurements and the values of the interfacial barriers determined in vitro to provide information about the mechanism of percutaneous absorption. The results indicate that for simple molecules the main route of penetration is via the intercellular channels. The model has been further applied to results from the literature and has been shown to be satisfactory in explaining the data.