Swelling and Ketoprofen Release Characteristics of Thermo- and pH-Responsive Copolymer Gels

Abstract

Swelling-controlled drug delivery copolymer gels were newly synthesized by introducing thermo- and pH-responsive methacryloyl-glycine (MA-Gly) or pH-responsive methacrylic acid (MA-Ac) for comparison with thermoresponsive acryloyl-L-proline ethyl ester (A-ProOEt). A homopolymer gel of A-ProOEt was kept at degrees of swelling that were less than 0.5 at a pH from 2.5 to 7.5 at 37°C. The thresholds of swelling for copolymer gels consisting of A-ProOEt/MA-Gly and A-ProOEt/MA-Ac with a composition of 40/60 mol% were found to be pH 3.0 and pH 5.5, respectively, in buffer solutions at 37°C. The diffusion characteristics of 2-(3-benzoylphenyl)propionic acid (ketoprofen) from such copolymer gels was evaluated in buffer solutions at pH’s more than 5.5, and it was found that A-ProOEt/MA-Gly gel possesses a case II transport mechanism that is completely linear time dependent in both the amount diffused and the penetrating swelling front position. On the other hand, A-ProOEt/MA-Ac gel exhibited a non-Fickian (or anomalous) diffusion behavior under the same conditions.