THE UTILIZATION OF BIOADHESIVE POLYMER LATICES AS VEHICLES FOR PROLONGING THE DELIVERY OF LOCALLY-ACTING DRUGS (LATEX)
Abstract
It was the purpose of this research to investigate the use of bioadhesive polymer latices and pseudolatices as delivery systems for improving the therapeutic efficacy of locally-acting drugs, with emphasis on prolonging the gastric retention of antacids. A procedure for interaction an insoluble antacid, magnesium oxide (MgO), with methylmethacrylate-methacrylic acid copolymer latices was developed, such that the antacid retained reactivity and the polymer its bioadhesive properties. Modifications of the technique were found useful for the entrapment of calcium carbonate and F-MA 11, a co-dried gel of aluminum hydroxide and magnesium carbonate. pH stat analysis indicated that certain acrylate copolymer latices decreased the rate of antacid reactivity, and titrigraphs of MgO-polymer interacted products were found to conform to biexponential reactivity profiles. A study on the effect of pH on the reactivity of selected interacted products indicated that a 20% methacrylic acid to methacrylate copolymer latex provided the greatest reduction in the rate of MgO reactivity. The pH stat was also used to determine the effect of formulation parameters on the rate of reactivity and the nature of the interaction for a polymer-MgO interacted product. The rate of MgO reactivity was found to be independent of the percentage of antacid in the interacted product up to approximately 70% MgO w/w, and the volume of methanol used to suspend a fixed amount of antacid did not significantly affect the nature of the interaction. Rossett-Rice test results also showed that acrylate copolymer latices with percentage of methacrylic acid below 30% improved the neutralization characteristics of MgO under simulated in vivo conditions. MgO powder reached a pH of 9.4 in less than 30 seconds and neutralized between pH 3 and 5 for only 10 minutes. In comparison, MgO-polymer interacted products of 30% methacrylic acid functionality reached a pH of 3.0 in less than 2 minutes and neutralized between pH 3 and 5 for nearly 60 minutes. An in vivo titrimetric assay was developed for quantifying the gastric retention of MgO-latex products in rats. The loss of reactive MgO from the stomach followed first-order kinetics. Neat MgO powder was found to have a gastric retention half-life of approximately 20 minutes. Certain MgO-polymer interacted products and half-life values over 100 minutes, indicating a significant prolongation in gastric retention of the antacid. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmacology
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