5-Aminosalicyclic acid permeability enhancement by a pH-sensitive EVAL membrane

A pH-sensitive membrane for colon-specific drug delivery was synthesized by the covalent bonding of glycine on the poly(ethylene-co-vinyl alcohol) (EVAL) membrane via isocyanation of surface hydroxyl groups and subsequent conversion to activated ester. The processes of surface modification would not change the membrane structure under the observable detection sensitivity of the scanning electron microscopy. Both the EVAL membrane and the glycine-immobilized EVAL membrane appeared as fairly dense structures almost without any holes existing in the membrane. Permeation of 5-amoinosalicylic acid (5-ASA) through the prepared membranes was studied at pH 2.0 and 7.4 at 37 ◦C. Regardless of the EVAL membrane and the glycine-immobilized EVAL membrane, the 5-ASA permeation at pH 2.0 was very conspicuously small, which agrees with the application of colon-specific drug delivery that drug is protected in the acidic environment. In contrast, the relative values of the 5-ASA permeation through the EVAL membrane and the glycine-immobilized EVAL membrane after 24 h at pH 7.4 and 2.0 were 6 and 41 times, respectively. Clearly, the significant increase in the 5-ASA permeability of the glycine-immobilized EVAL membrane is suitable for local treatment of ulcerative colitis. Furthermore, the mechanism of 5-ASA permeation through the EVAL membrane and the glycine-immobilized EVAL membrane at pH 2.0 and 7.4 was discussed. This study shows the 5-ASA permeability enhancement by the EVAL and the glycine-immobilized EVAL membrane in the neutral environment is ascribed to totally different mechanisms. © 2002 Elsevier Science B.V. All rights reserved.