Monitoring the Penetration and Distribution of Topically Applied Formulations through the Skin in Relation to the Skin Protein/Lipid Morphological Characteristics

Abstract

The ability of topically applied dosage forms to penetrate the skin depends on the interactions of the formulation ingredients with the intrinsic components of the skin. These interactions define the penetration route as well as the distribution of the drug in the skin tissue. The present study focused on monitoring components of externally applied formulations through the skin (ex vivo) via mid-infrared microspectroscopic techniques. Infrared microspectroscopy represents a new bioanalytical method, combining the powerfulness of chemical component analysis by means of infrared spectroscopy and using the high lateral resolution (∼20 µm) as obtained from microscopy. Two methods are applied for analysing tissues: the mapping and the imaging approach. A major breakthrough using infrared microspectroscopy in tissue diagnostics was the development and implementation of so-called focal plane array detectors. Using these detectors, sample areas of about 0.25–16 mm2 can be analyzed. The highest lateral resolution obtained by the transmission techniques approaches the mid-infrared diffraction limit of approximately 6 µm. Using mid-infrared microspectroscopic imaging, a large amount of biochemical information, at high lateral resolution, is generated, not yet available by other methods. Additional advantages are: it is a non-invasive, non-destructive approach, requiring no complex and time-consuming tissue staining procedures. In the present study, mid-infrared microspectroscopic mapping and imaging techniques in transmission are used for the biochemical characterisation of skin samples (e.g. lipid/protein distribution). This information provides new insight into the morphology of the tissue constitution. Additionally, examples are presented concerning the analysis of the distribution of topically applied drugs (e.g. UV B blocker or liposomes) through the skin. The potential as well as the limits of the methods for dermatological research are discussed.