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Title: Dermatopharmacokinetics and pharmacodynamics of topical glucocorticoids
Author: Wiedersberg, Sandra.
ISNI:       0000 0001 3567 8776
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2006
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Abstract:
The efficiency of topical drug delivery is notoriously poor, with typical bioavailabilities of only a few percent of the applied dose. A major reason for this disappointing situation is the absence of a quantitative and validated methodology (apart from the vasoconstrictor assay for topical glucocorticoids) with which to quantify the rate and extent of drug delivery to a target into the skin. In an attempt to address this situation, significant efforts are being directed to the dermatopharmacokinetic (DPK) approach using tape-stripping. The main objective of this thesis, therefore, was to compare the in vivo bioavailability profiles of betamethasone 17-valerate (BMV) assessed using the vasoconstrictor assay and the DPK approach. Furthermore, the ability of these two methods to distinguish between different formulations as well as different concentrations was examined. As the DPK approach is currently under critical re-evaluation, different cleaning procedures of the skin before tape-stripping were compared and evaluated. Moreover, the influence of the viscosity of the formulation on the DPK results was also determined. In addition, the effect of the vehicles on skin hydration was studied. Applying different BMV concentrations resulted in a clear concentration dependence of the skin blanching response until saturation of the response occurred. Upon this saturation effect, any changes between different formulations and between concentrations could no longer be observed. Due to the saturable nature of the skin blanching response, the interpretation of the data has to be considered with care and, therefore, it is important to operate in the linear part of the ‘dose-response’ curve, whenever quantitative conclusions about bioavailability are to be drawn. The DPK approach, on the other hand, showed reasonable reproducibility and distinguished clearly between different formulations and different BMV concentrations applied; it appears to offer a reliable metric, therefore, with which to quantify topical bioavailability. The cleaning procedure, as well as the viscosity of the formulation applied, have a significant influence on the apparent extent of drug delivery into the stratum corneum. Excess formulation, especially from semi-solids, may be trapped in the skin ‘furrows’ and requires an efficient skin cleaning procedure to ensure its complete removal. Overall, the DPK technique merits continued evaluation and optimization as a tool for the quantification of topical bioavailability and bioequivalence. These steps are essential for the ultimate objective of validating the results of DPK experiments against credible clinical data.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.436793  DOI: Not available
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