Bhuiyan, A.K.M.M.H. (2016) A comparative study of chemical based skin mimics with pharmaceutical applications. Doctoral thesis, University of Huddersfield.

The prediction of percutaneous absorption is of enormous importance for the effective design, development and quality assessment of topical and transdermal formulations. In vitro diffusion experiments are widely carried out for such predictions and are of substantial interest across the pharmaceutical and cosmetic industries. Human or animal skin, usually excised, are often used in in vitro drug diffusion studies. However, difficulties in obtaining the mammalian skin and variation in their permeability directed researchers towards using synthetic membranes as skin mimics in preformulation screening experiments, where a large number of experiments are required. Polydimethylsiloxane (PDMS) membranes have been accepted as the most commonly used in vitro skin mimic because of their homogeneity, uniformity and skin-analogous rate-limiting permeation properties.

This thesis investigates the effects of ionisation and surfactants on the permeation of pharmaceutical compounds of varied physicochemical properties through PDMS membranes using a flow-through diffusion cell system. Data suggests that drug permeation had a dependency on the extent of its ionisation, with the permeation being more favourable for the more unionised form of a drug. All of the surfactants studied were found to reduce the permeation of the drugs, with an inverse relationship being observed between the surfactant concentration and the amount of drug permeated. DSC (differential scanning calorimetry), SEM (scanning electron microscopy), FTIR (Fourier transform infrared) and NMR (nuclear magnetic resonance) spectroscopy were employed to study the interactions between the membrane and the surfactants. Results indicated that the permeation effects of the surfactants are a consequence of the interactions between the drugs and surfactant micelles, and/or the membrane and the surfactants.

Air plasma treatment was used to modify the PDMS surfaces to become hydrophilic, which was confirmed by water contact angle (WCA) and SEM-EDX analysis. The permeation data for the modified membranes revealed that the plasma-induced hydrophilicity significantly reduced the fluxes of the hydrophobic compounds, while not affecting that of the hydrophilic drug. Aging studies of the plasma-treated membranes showed that the hydrophilic surfaces were maintained even after 8 weeks under airtight storage conditions.

In summary, ionisation and surfactant effects on drug permeation across PDMS were thoroughly investigated, and plasma treatment was found to be a stable, economic and convenient method of modifying PDMS to offer skin-like slower drug permeation i.e. to produce a potential in vitro skin mimic.

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