Date of Award

1993

Degree Type

Dissertation

Degree Name

Doctor of Pharmacy (PharmD)

First Advisor

Walter Muller

Abstract

The effect of nifedipine saturation solubility in several cosolvent systems on nifedipine permeation through hairless mouse skin is evaluated. The effects of patch components is measured by (1) identifying those factors which significantly affect the permeation of nifedipine and (2) selecting settings for these factors which optimize flux and lag times. Of particular interest is the application of solubility theory toward the estimation of theoretical partition coefficients which were, it turn, useful in predicting the effect of donor composition on nifedipine permeation. A stoichiometric approach was taken to examine the influence of permeation enhancers on skin permeability of this calcium channel blocker. Inherent in this approach is that a change in one component requires collateral change in the next; a deficiency best handled by an experimental design of the mixture type. The ultimate objective was to apply regression techniques to interpret, on a molar basis, the data obtained from in vitro permeation experiments. The model obtained was employed to: (I) identify both the magnitude and significance of synergism between formulation components and (2) optimize the desired response. Data from these inquiries have contributed toward the rational selection of components in a viable transdermal dosage form.

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