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Quantitative structure/skin-permeation relationships (QSPeRs); an investigation of the relevance of parameters determined with biomembrane-mimicking systems for the predictability of drug partitioning into skin


About This PhD Project

Project Description

The transdermal route has many advantages over other routes for the delivery of drugs with systemic activity. These include the ease of use (and withdrawal in the occurrence of side-effects), avoidance of first-pass metabolism, and improved patient compliance. The assessment of percutaneous absorption of molecules is a very important step in the evaluation of any transdermal drug delivery system. The most reliable skin absorption data are obtained in human studies.

However, such studies are virtually impossible due to ethical difficulties and high cost, particularly during the early stage of new drug candidate development. Hence the development of reliable quantitative structure/skin-permeation relationships (QSPeRs) which predict precisely transdermal delivery is of great interest and importance in industrial, regulatory, and academic circles [1]. It is also of great importance to find formulation strategies to improve skin permeability for poorly permeable drugs. Quantitative structure/skin permeation relationships (QSPeRs) relate the experimentally determined percutaneous penetration of exogenous chemicals to known physicochemical parameters using standard statistical methods. QSPeRs provide insights into permeation mechanisms, can predict the permeation of novel compounds even when they exist only on paper, and reduce or eliminate the need for in vivo experiments.

Projects aims

• Develop a reliable QSPeRs model by relating skin permeabilities from human skin in vitro to known physicochemical parameters (lipophilicity index, H-bonding groups values and polarity), and thus to clarify the mechanism of permeation
• Determine which biomembrane-like system provides an index which best correlates to biopartitioning of drugs into skin membranes
• Assess the effect of formulation excipients on the QSPeRs model
• Investigate formulation strategies to improve skin permeability of low permeable drugs

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