CROSSLINKED POLY (METHYL VINYL ETHER/MALEIC ANHYDRIDE) COPOLYMERS AS CONTROLLED RELEASE PHARMACEUTICAL FILM COATINGS (POLYMETHYL)
Abstract
An investigation was undertaken to study the feasibility of coating tablets with a polymeric crosslinked film system which would provide controlled or sustained release properties, by the leaching of drug molecules through an intact film. Poly (methyl vinyl ether/maleic anhydride) 169 copolymer (PVM/MA) in combination with a crosslinking agent (Tween 20, polyethylene glycol, or ethylene oxide) and plasticizer, triancetin, were used to prepare free and applied insoluble films which were evaluated for their permeability properties. The films were pretreated in a 52% relative humidity chamber at 40(DEGREES) in order to enhance the esterification reaction which results in a crosslinked film system. Increasing Tween 20 concentrations resulted in a decrease in the permeability of amaranth through free and applied film systems. Increasing concentrations of the plasticizer, triacetin, resulted in a slight decrease in permeability. The amount of Tween removed from PVM/MA 169 free film systems, crosslinked with varying concentrations of Tween appeared to be a linear function based on the percent of Tween in each film system. Polyethylene glycol crosslinked film systems were found to exhibit permeability properties similar to those of Tween crosslinked films, but were not as strong as Tween films and ruptured more frequently. An increase in the molecular weight of the PEG generally resulted in an increase in the permeability of the film. The permeation rate of Tween, polyethylene glycol, and ethylene oxide crosslinked films appeared to be a linear function of the swelling of the films irregardless of the amount or type of crosslinker employed. Tablets coated with concentrations of PEG and Tween 20 crosslinker greater than 2 parts t 8 parts of polymer ruptured within 2 hours in a buffer solution of pH 1.30. Film coated tablets had a lower permeation rate than the same free film systems. This lower permeation rate was probably lrgely due to slow penetration of the solvent into the matrix and the time required for the dissolution of the amaranth in the tablet matrix. In vivo radiographic analysis of tablets coated with 8-0.5-5 and 8-1-5 parts of PVM/MA 169, Tween 20, and triacetin, respectively, showed that the tablets swelled over a period of 1/2 to 4 hours. Tablets with a heavy coat of polymer (approximately 30 mg.) were observed to have very prolonged gastric residence times, remaining intact in the stomach for up to 7 1/2 hours. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
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