De Oliveira Mateus, R; (2014) Spectroscopic and membrane transport evaluation of model topical formulations. Doctoral thesis , UCL ( University College London).

Abstract

This thesis addresses the dynamics between drug, solvent and membranes and the challenges in overcoming the stratum corneum barrier using different chemical penetration enhancers. Although the mechanisms of skin penetration have been subject of research for many decades, there are a lot of questions yet to be answered. The purpose of this investigation was to give insight about the mechanisms of partition and diffusion of a drug into the membrane. Synthetic membranes are a useful and cheap approach to understand those mechanisms owing to their low complexity compared to human tissue. Solubility, solvent uptake and evaporation behaviour of the solvents were performed to study interactions between solvents, actives and membranes. These interactions will dictate the permeation and delivery of actives. Furthermore, spectroscopic techniques such as ATR-FTIR were of extreme importance for the further investigation of solvent-membrane interactions and also to study the diffusion of different species (solvents and actives) across silicone membranes. Assessment of permeation using more complex membranes such as porcine ear skin, which have been shown to be good models to assess drug permeation, includes in the experiment, the complexity inherent to biological tissue. Understanding the permeation of actives and solvents in vitro is the first step to understand drug delivery in vivo. A recent spectroscopic technique allows the non-invasive investigation of real time drug delivery in vivo. Confocal Raman spectroscopy allows the profiling of actives inside the skin and is able to differentiate between formulations therefore expanding our understanding of the mechanisms involved in drug absorption after its application to the SC. The findings indicate the formulation components play a crucial role in the delivery of actives in vitro and in vivo and an informed selection of solvents is one of the strategies to design optimal topical formulations.

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