Abstract
Abstract A new rationale 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°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.
Published Version
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