THE RELATIONSHIP BETWEEN THE PHYSICOCHEMICAL PROPERTIES OF COPOLYMER LATEX COAGULA AS POTENTIAL DRUG CARRIERS AND THEIR BIOADHESION AND GASTRIC RETENTION

GREGG WALTER RICHMOND, Purdue University

Abstract

An evaluation of the physicochemical properties of methylmethacrylate-methacrylic acid copolymer latices affecting their gastric retention in rats, was undertaken. The polymer latex products were dosed either as a ('14)C-labeled product or as a product containing fluorescein as a marker. The retention of these products was measured as 6 hours post dosing by counting the radioactivity or measuring the quantity of fluorescein in the stomach. The half life for gastric emptying of an alcohol addition coagulated E896 polymer emulsion was found to be approximately 7 hours, which was much larger than literature values for liquid test meals and ordinary meals. The retention of this polymer was found to be much larger than several control materials at 6 hours post dosing. The effects of the {COO('-)}, the surface carboxyl content or surface binding sites, solvent uptake, density and particle size of the polymer products on the gastric retention of the products was studied. The effect of the method of coagulation of the polymer latex on the gastric retention of the resulting products was also studied. The coagulation of the polymer latex was the most significant factor affecting gastric retention. The coagulated products, whether coagulated by an alcohol addition method, an electrolyte addition method or by a precipitation in an hydroalcoholic dispersion, were retained to a greater extent at 6 hours post dosing than the products that were not coagulated. This was hypothesized to be related to the naure of the polymer being changed by coagulation such that it would not dissolve or redisperse readily. The next most significant factor was found to be the surface carboxyl content or binding sites of the polymer product. As the surface binding sites increased, the amount of polymer retained in the stomach also increased. This was proposed to be a result of the carboxyl groups and/or other binding sites being binding sites for gastric mucin, which then bound the particles to themselves and the stomach wall. Additional studies were performed showing that mucin did in fact bind with the available groups on the polymer products. Particle size of the polymer product was also shown to influence gastric retention of the products. It was found that as the particle size decreased the amount of product retained also decreased. This was thought to be related to an increase in dissolution rate as result of increased surface area with decreased particle size. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI

Degree

Ph.D.

Subject Area

Pharmaceuticals

COinS