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Date of Award

2001

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Xiaoling Li

First Committee Member

Bret Berner

Second Committee Member

Donald Floriddia

Third Committee Member

Paul Williams

Abstract

Hydrogel membranes with different charge properties, positively charged 2-(N, N-Dimethylamino)ethyl methacrylate-co-butyl acrylate (DMEMA-co-BuA), neutral 2-hydroxyethyl methacrylate-co-butyl acrylate (HEMA-co-BuA), and negatively charged acrylic acid-co-butyl acrylate (AA-BuA) were designed and synthesized for investigation of the transport mechanism of iontophoresis. The hydrogels were characterized by determination of the equilibrium hydration and dimensional change. To study the different crucial factors influencing iontophoretic transport, three model compounds, positively charged phenylpropanolamine (PPA), zwitterionic phenylalanine (Phe), and negatively charged 3-phenylpropionic acid (3-PPA) were selected. These compounds have similar structure and molecular weight but different charge properties. Three transport conditions, passive diffusion, anodal and cathodal iontophoretic transport, were used in this dissertation. A novel parameter, E v , was developed to quantitatively evaluate the enhancement of transport due to the electro-osmotic flux. E v values were obtained by comparing the enhancement/hindrance factor (E-value) through charged membrane to that through neutral membrane with comparable hydration. The model compounds, hydrogel membranes, and transport conditions used in this study made the iontophoretic transport a complicated system with twenty-seven possible different combinations. The E v values can be used to determine the electro-osmotic effect under various iontophoretic conditions with different permeants. The results showed that E v values of permeants with similar structure and molecular weight are robust to permeant charge. Passive diffusion and anodal/cathodal iontophoretic transport of PPA through HEMA-co-BuA and AA-co-BuA of different compositions were conducted. Linear relationships were established between the reciprocal of hydration and the logarithm of flux, E-value, and E v value. It is found that iontophoretic transport of drug through hydrogels is governed by free volume theory. To explore the pH effect on iontophoretic transport through hydrogel, the transport behaviors of Phe through HEMA-co-BuA under three transport conditions in the pH range of 1.5 to 11.2 were investigated. A mathematical model was developed to describe the effect of pH on iontophoretic transport. This model has successfully predicted the total permeability of Phe at various pH values. The distribution and charge of species depended on pH and thus affected iontophoretic transport. The passive, anodal and cathodal transport behaviors of 3-PPA through negatively charged human skin were in agreement with those through the negatively charged hydrogel membrane AA-co-BuA (60:40). It was shown that the negatively charged hydrogel membrane could be used as a model membrane to study transport behavior through human skin.

Pages

197

ISBN

9780493155173 , 0493155171

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