Bimodal release of ibuprofen in a sustained-release formulation: a scintigraphic and pharmacokinetic open study in healthy volunteers under different conditions of food intake

Abstract

The position of a radiolabelled sustained release ibuprofen formulation containing 800 mg drug and labelled by the addition of 10 mg [ 111In] ion-exchange resin has been followed by gamma scintigraphy in 11 healthy male and female volunteers. The study was conducted first in 5 volunteers who received the tablet with a light breakfast and then as a cross-over study in a separate group of 6 volunteers who had either fasted or ingested a heavy breakfast. Mean times ( ± S.D.) for gastric emptying of the unit were 1.0 ± 0.4 h (fasted, n = 6), 2.0 ± 0.9 h (light breakfast, n = 5) and 8.8 ± 5.9 h (heavy breakfast, n = 4). There were no significant was observed to remain intact until it reached the ascending and transverse colon where it broke into two or three pieces or completely disintegrated. In two subjects, in which the tablet had been administered with a heavy meal, the unit remained in the stomach for more than 15 h. The presence of food markedly altered the pharmacokinetics of the drug which, in fasting subjects, was characterised by a double peak in the plasma concentration time profile. The light breakfast caused a levelling of the two peaks to a plateau lasting from 4 to 13 hours, whereas after the heavy breakfast only the secondary peak was evident. The secondary peak appears to be due to a disintegration of the matrix after 12–14 h coupled with a high absorptive capacity for the drug in the ascending colon. There was no evidence of adhesion of the unit to the gastrointestinal mucosa.