| Summary: | Mid Infrared spectroscopy coupled with multivariate Target Factor Analysis (TFA) was used to investigate permeation and localisation of drugs through and within synthetic membranes and human skin. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy was used for the diffusion experiments, and Mid-IR mapping for the drug distribution studies in human skin. A proof of concept was established through these studies, for a rapid screening protocol of membranes in general. Mid-IR reference spectra of the compounds were systematically collected to form a library for subsequent data interpretation. Reproducibility studies using a solution of methyl paraben (MP) in ethanol (EtOH) and water through Carbosil and polydimethylsiloxane (PDMS) or silicone were conducted. Carbosil membrane is more complex membrane than PDMS as it has a heterophase domain structure composed of PDMS and polycarbonate (PC). It was found that an extremely good contact between the membrane and the ATR crystal was essential in order to obtain good reproducibility. Carbosil had an excellent contact and thus good reproducibility was obtained, whereas the opposite was found for the type of silicone membrane used. Also, the power of TFA to deconvolute very similar compounds such as MP and propyl paraben (PP), within a same data set, was successfully demonstrated. Diffusion experiments on a series of model drug compounds, i.e. methyl paraben (MP), ibuprofen (IBU) and caffeine (CF) in water and ethanol were studied through a synthetic membrane and human skin. The spectral data collected were complex, and were therefore, analysed by multivariate TFA. The data were successfully deconvoluted obtaining, in most of the cases, a high correlation between the deconvoluted factors from the data and the reference spectra of the compounds of interest. then evolution profiles for the diffusion of the species with time for the drug, and solvents were obtained for Carbosil as well as for skin, even though in the case of the skin the data were still more complex. A commercial formulation of IBU was also examined using human skin. Again most of the components were successfully deconvoluted and evolution profiles were obtained. Finally, Mid IR and TFA was used to localise a lipophilic drug within the layers of human skin. The distribution and localisation of the drug in the skin layers was successfully studied by adopting a multivariate analysis approach based on TFA. The compound was successfully localised and the greatest relative concentration was observed within hair follicles as expected. The ensemble of these experiments demonstrates that IR spectroscopy coupled with TFA is a valuable tool for the study of membranes, particularly skin. It also opens up a novel approach to high throughput screening in formulation development.
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