A NOVEL-APPROACH FOR PREPARATION OF PH-SENSITIVE HYDROGELS FOR ENTERIC DRUG DELIVERY

A new rational of preparing pH-sensitive hydrogels based on thermally reversible polymers is proposed, according to which a new class of hydrogels has been synthesized. These special gels are sensitive to both temperature and pH, and respond to the pH change to a much greater extent than hydrogels based on poly(hydroxyethyl methacrylate-coacrylic acid) or poly(acrylamide-co-acrylic acid) hydrogels. At 37-degrees-C, they are above their lower critical solution temperature when uncharged. Therefore, at gastric pH (1.4), these gels contain only a moderate amount of water, all of it as bound water. But at enteric pH (6.8-7.4), they swell extensively, permitting sustained enteric delivery of drugs such as indomethacin, which would otherwise cause stomach irritation. An in vitro study has shown that only a negligible amount of indomethacin is released at pH 1.4 in 24 hours, while at pH 7.4 more than 90% of the total drug in the gels is gradually released over ca. 5 hours. The release rate at pH 7.4 increases with the fraction of non-freezing, free water in the gels, which is in parallel with the gel acrylic acid content. An anomalous release profile was observed for all the pH-sensitive heterogeneous hydrogels at this pH, suggesting a swelling-controlled mechanism.