Dissertation

Investigation of factors affecting skin penetration in vitro

Green, Darren Michael

2006

Overview

When desirable retardation of skin penetration of toxic compounds such as pesticides and chemical warfare agents was evaluated using model permeants, retardation was observed under certain conditions, but was not predictable. It was concluded that generic penetration modulation was not a realistic goal. Investigations into skin surface sampling techniques highlighted the difficulties of minimising variability, and comparison of in vitro tape stripping with published in vivo data for a clobetasol propionate cream demonstrated the significance of formulation inhomogeneity. Determination of orally administered doxycycline in the stratum corneum using in vivo skin surface biopsies suggested that it was unlikely that this technique could be of value for most orally administered drugs. Evaporative loss of volatile permeants, such as fragrances, during skin penetration studies makes it impossible to achieve full mass balance. Direct capture of evaporating material was occlusive and significantly affected the amount that permeated through the skin membranes. A simple novel method was therefore developed to allow estimation of evaporative loss under the experimental conditions. Pre-study skin water permeability coefficient (Kp) is frequently used as a membrane integrity check and it is generally assumed that skin of higher water permeability will be of higher permeability for subsequently applied compounds, regardless of differing physiochemical properties. However, it was shown that Kp did not correlate with subsequent test compound permeation for twelve compounds of moderate to high lipophilicity.

• Publisher: ProQuest Dissertations & Theses
• Subject: Physiology
• ISBN: 107325142X, 9781073251421