2000 年 60 巻 2 号 p. 128-138
In vitro dissolution test conditions to obtain good IVIVCs for slow release enteric-coated pindolol granules were investigated by applying the GE-convolution method that convoluted in vitro dissolution and the GI transition of granules. Four kinds of enteric coated granules were prepared by a combination of two different enteric coatings and two core granules having different dissolution rates. Sustained-release dosage forms consisting of immediate release granules containing 5 mg of deuterium-labeled pindolol and enteric-coated granules containing 10 mg of unlabeled pindolol were administered to healthy volunteers. The plasma concentrations of labeled and unlabeled pindolol were simultaneously determined by the GC-MS selective ion monitoring method, and cumulative absorption profiles of the enteric-coated granules were calculated by the Wagner-Nelson method by using the pharmacokinetic parameters of immediate release granules. The dissolution profiles of the enteric-coated granules in the GI tract were simulated by applying the GE-convolution method to in vitro dissolution profiles in different pH test solutions. As a result, when the pH of the test solution was 5.5, good IVIVC was observed under various food conditions. The GE-convolution method, which can simulate an absorption profile from a dissolution profile obtained under appropriate dissolution test conditions, is considered useful not only for designing enteric-coated granules having optimal dissolution rate, but also for evaluating the efficacy of the drug product
