Date of Degree

2011

Document Type

PhD diss.

Degree Name

PhD (Doctor of Philosophy)

Department

Pharmacy

First Advisor

Dale E. Wurster

Abstract

The drug metoclopramide was found to adsorb to the unionized and ionized silica surface. The primary objective of this research was to use potentiometric titration in order to study the specificity of the interactions of benzamide analogs with the hydroxyl groups, silanols, on the Aeroperl® silica surface.

Mass titration studies showed that the acidity of surface silanols increases with dissolved metoclopramide and similar compounds. The nature of the interaction was concluded to involve a physical adsorption process. A different potentiometric titration method was devised to determine the ionization of silanols in the presence of a dissolved compound with solubility limitations. This method was found to give similar results as that described in the literature. The presence of dissolved metoclopramide was found to cause a large increase in the density of the negatively charged silanols on the silica surface. The ionization of silica was dependent on the concentration of dissolved metoclopramide at low pH but was found to be constant over a wide concentration range at pH 7.0 or higher. Adsorption studies with unionized silica indicated that specific interactions with the surface silanols occur as well as non-specific interactions driven by hydrophobic bonding with the surface siloxane groups. There was an increase in the adsorption of metoclopramide with increasing ionization of the silica surface which suggested that the negatively charged silanols constituted an additional adsorption site.

The mechanism of the interaction was elucidated by potentiometric titration with various probe compounds. The titration data with lidocaine suggested that the ionization of the surface silanols is influenced by specific interactions with the adsorbed compound rather than concentration effects. The ionized site density of silica was found to be related to the relative magnitude of the aromatic π-electron density of the adsorbed benzamides. A comparison of these titration data with that of triethylamine indicated that ionic interactions between the positively charged amine groups and the negatively charged silanols are likely to be occurring. Based on the difference in chemical structure, the titration data with dissolved ephedrine indicated that the other site of interaction is likely to be between the carbonyl oxygen of the adsorbed benzamides and the unionized silanols. The pH dependence of the ionization of silanols for both adsorption sites suggested that silanols interact simultaneously with several functional groups on a single adsorbed molecule.

Pages

xxxiv, 491

Bibliography

485-491

Copyright

Copyright 2011 Tuba Buyuktimkin