Oxybutynin permeation in skin: the influence of drug and solvent activity.
The influence of degree of saturation (DS) of oxybutynin on permeation from octyl salicylate (OSAL) or propylene glycol (PG) vehicles was investigated, in vitro, in human skin. The permeation of OSAL and PG was also evaluated and the quantity of drug and solvent in the skin at the end of the diffusion study was measured. For OSAL the permeation of oxybutynin increased linearly with DS of drug for both 25 and 50% OSAL formulations. However, no differences were seen in oxybutynin permeation for formulations with the same DS but with different OSAL amounts, although the drug permeation was always slightly higher for 50% OSAL formulations. There was a decrease in the amount of OSAL extracted from skin with drug concentration (up to 5 DS). There was also a good correlation between the DS calculated from the amount of oxybutynin and OSAL extracted from the skin, and the actual DS of the formulation. In contrast oxybutynin DS did not affect PG permeation and there were no significant differences in oxybutynin permeation for the formulations with different DS. The lack of permeation enhancement for PG formulations appears to be related to PG depletion from the skin. The findings emphasise the importance of maintaining the drug in solution in order to achieve effective permeation from dermal and transdermal formulations.
Santos
P
P
Department of Pharmaceutics, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Watkinson
A C
AC
Hadgraft
J
J
Lane
M E
ME
D000279:Administration, Cutaneous; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008333:Mandelic Acids / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*; D012997:Solvents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*
D008333:Mandelic Acids; D012997:Solvents; C005419:oxybutynin