skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Bioadhesive polymers as platforms for oral controlled drug delivery II: synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers

Journal Article · · J. Pharm. Sci.; (United States)

A series of cross-linked, swellable polymers was sythesized from monomers such as acrylic acid, methacrylic acid, and others with various cross-linking agents to produce a range of polymers differing in charge densities and hydrophobicity. The densities, rate, and extent of hydration of the polymers were determined. An increase in the number of hydrophobic groups in the polymer structure reduced hydration whereas the density of the polymer was unaffected. A sensitive in vitro method for measuring adhesion of polymer to tissue from the rabbit stomach was developed. Polymers of acrylic acid loosely cross-linked (0.3%, w/w) with three different agents, divinyl glycol, 2,5-dimethyl-1,5-hexadiene, and divinylbenzene, showed the same degree of bioadhesion while poly(methacrylic acid-divinylbenzene) showed reduced bioadhesion. The small percent of cross-linking agent, irrespective of physicochemical properties, did not contribute substantially to bioadhesion, whereas the starting monomer had a large effect. The effect of pH on the bioadhesion of poly(acrylic acid-divinyl glycol) was studied at constant temperature, ionic strength, and osmolality. The polymer showed maximum adhesion at pH 5 and 6 and a minimum at pH 7. Gastrointestinal transit studies of cross-linked polymers in rats were studied. Poly(acrylic acid-divinyl glycol) and poly(methacrylic acid-divinylbenzene) were shown to have substantially longer GI transit times than the control, Amberlite 200 resin beads. The delay in transit time was due to bioadhesion of the polymer to the mucin-epithelial cell surface which was clearly observable on animal autopsy. The acrylic acid polymer showed a longer GI transit time than the methacrylic acid polymer, and this in vivo GI transit result is consistent with in vitro bioadhesion test results.

OSTI ID:
5010920
Journal Information:
J. Pharm. Sci.; (United States), Vol. 4
Country of Publication:
United States
Language:
English