Skin, more specifically the outermost skin layer, the stratum corneum (SC), forms an extremely effective barrier, preventing both the loss of heat and water, and the ingress of micro-organisms and chemicals. Assessing the rate and extent of drug permeation into or through the skin is important both to evaluate the usefulness of a drug for topical or transdermal delivery, and to compare different formulations to assess their bioequivalence. Prediction of drug permeation is logistically, ethically and economically preferable to in vivo measurements. The recent progress that has been made with empirical and mechanistic mathematical models, along with in vitro diffusion cell techniques has been reviewed. However, currently, in vivo measurements, in man, are still required. For new chemical entities, the need for clinical trials is clear. In the case of generic products, however, there is considerable effort currently being expended to replace expensive, subjective clinical trials with objective, validated measurements of drug permeation, in vivo, in particular to assess bioequivalence. The tape stripping technique has emerged as a promising technique to objectively measure drug permeation through skin, and is the focus of this thesis. After formulation application and removal, layers of SC are sequentially removed by adhesive tapes. As the SC performs the main barrier function of the skin, measuring the rate and extent of drug permeation through this layer is assumed to be related to overall topical bioavailability. The work in this thesis concentrates on performing tape stripping studies such that all tapes are analysed individually, and drug concentration as a function of SC depth is measured. The concentration depth profiles across the SC may be fitted to an appropriate solution of Fick's second law of diffusion to obtain estimates of the vehicle-SC partition coefficient and the drug's diffusivity in the membrane. These dermato-pharmacokinetic parameters may be compared for different formulations.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:512306 |
| Date | January 2008 |
| Creators | Russell, Lisa Maria |
| Contributors | Guy, Richard |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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