1998 年 58 巻 3 号 p. 116-124
The purpose of this study was to seek good in vitro-in vivo correlation (IVIVC) for enteric-coated multiple unit dosage forms. The gastric emptying (GE)-convolution method we had developed was applied to analyze data from bioavailability tests of enteric-coated aspirin granules that had been conducted with eight healthy male volunteers, four subjects having orthotonic stomachs and four hypotonic stomachs. Enteric-coated aspirin granules and enteric-coated BaSO4 granules were administered concurrently, and the concentrations of salicylate in serum and urine were determined. The behavior of the BaSO4 granules was traced by X-ray camera. The dissolution profiles of enteric-coated aspirin granules in the gastrointestinal (GI) tract were determined by combining in vitro dissolution data and gastric-emptying profiles of granules (GE-convolution). The cumulative absorption profiles of aspirin under usual and light meal conditions, calculated by the Wagner-Nelson method, closely coincided with the predetermined dissolution profiles from in vitro dissolution at pH 5.0. Dissolution profiles in vivo were successfully predicted by this novel method, which takes into account the great change in the gastric emptying rate of granules caused by food and interindividual variation.
