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Strategies for optimizing percutaneous absorption

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Siddiqui, O 1987 , 'Strategies for optimizing percutaneous absorption', PhD thesis, University of Tasmania.

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Abstract

Studies were carried out on the in vitro permeation of steroids and weak electrolytes through the human stratum corneum. Diffusion and compartmental models were used to describe the mechanism of permeation of the ionised and unionised moeities of the above drugs. The effect of iontophoresis and the pH of aqueous vehicles on the rate and extent of permeation of weak electrolytes was also investigated. The relative contribution of epidermal and dermal transport of methotrexate and steroids was examined in an attempt to define the concentration of these drugs likely to be found in the viable epidermis.
The results obtained using mathematical models suggest that the main route of skin penetration of both steroids and weak electrolytes through the excised human stratum corneum is more likely to be through the "intracellular" route than through the "shunts". The present work using diffusion and compartmental models suggests that both ionised and unionised species of weak electrolytes can permeate the excised human stratum corneum. There is evidence to indicate the presence of a "pH-shift" for some weak electrolytes and that the ionised species of weak electrolytes form an ion pair with counter ions present in a vehicle. The formation of an ion pair and its ability to partition into the lipid phase with relative ease also indicates that ionised species of weak electrolytes are likely to penenrate the excised human stratum corneum through the "intracellular" route.
In the absence of iontophoresis, the rate of penetration of weak electrolytes was greatest at a pH value where the substance was mainly in the unionised form; iontophoresis was most effective at a pH value where the weak electrolyte was mainly in the ionised form. It is postulated that during the application of iontophoresis the "shunt" pathway could be the major route of skin penetration.
The rate of dermal disappearance of methotrexate and steroids was found to depend on both the dermal blood supply and the rate of diffusion into the dermis. It was found that the epidermal penetration rate and dermal clearance play a significant role in determining the concentration of a drug likely to be achieved in the viable epidermis. The present results suggest that high dermal clearance may reduce the efficacy of topically applied medication.

Item Type: Thesis - PhD
Authors/Creators:Siddiqui, O
Keywords: Skin absorption, Steroid drugs, Electrolyte therapy
Copyright Information:

Copyright 1985 the author - The University is continuing to endeavour to trace the copyright owner(s) and in the meantime this item has been reproduced here in good faith. We would be pleased to hear from the copyright owner(s).

Additional Information:

Thesis (PhD)--University of Tasmania, 1987. Bibliography: leaves 146-173

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