Thermo- and pH-responsive gels for application in colon delivery systems

Swelling-controlled drug delivery copolymer gels were synthesized by introducing thermo- and pH-responsive methacryloyl-glycine (MA-Gly) of pi-I-responsive methacrylic acid (MA-Ac) into thermo-responsive acryloyl-L-proline ethyl ester (A-ProOEt). The threshold of swelling for copolymer gels consisting of A-ProOEt/MA-Gly and A-ProOEt/MA-Ac with a composition of 40/60 mol% was found to be pH 3.0 and pH 5.5, respectively, in buffer solutions at 37 degrees C. The diffusion characteristics of 2-(3-benzoylphenyl)propionic acid (ketoprofen) from such copolymer gels were evaluated in buffer solutions at pHs more than 5.5, and it was found that A-ProOEt/MA-Gly gel possessed a Case II transport, while the A-ProOEt/MA-Ac gel exhibited a non-Fickian (or anomalous) diffusion behavior under the same conditions. (C) 1999 Elsevier Science Ltd. All rights reserved.