Correlation of Ibuprofen Bioavailability with Gastrointestinal Transit by Scintigraphic Monitoring of ¹⁷¹Er-Labeled Sustained-Release Tablets

Abstract

External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of ¹⁷⁰Er₂O₃ (enriched to >96% ¹⁷⁰Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in a neutron flux (4.4 × 10¹³ n/cm² · sec) for 2 min, converting the stable ¹⁷⁰Er to radioactive ¹⁷¹Er (t _1/2 = 7.5 hr). Each tablet contained 50 µCi of ¹⁷¹Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance.