Ibuprofen and pseudoephedrive hydrochloride as granules for oral solution. A comparative pharmacokinetic study

Abstract

Introduction: Conventional oral formulations can be difficult to swallow for patients with dysphagia, children, and the elderly. A new pharmaceutical form containing a combination of ibuprofen/pseudoephedrine designed to provide easier administration and more flexible dose adjustment while maintaining similar pharmacokinetic profile to other conventional formulations already on the market was developed. The objective of this study was to evaluate the bioequivalence of a fixed oral combination of 400 mg ibuprofen and 60 mg pseudoephedrine granules for oral solution, compared with a reference market standard formulated in soft capsules after single dose administration. Methods: An open, randomized, single dose, two-period, crossover trial was conducted. Subjects were randomly assigned to receive either 1 sachet of granules for oral solution (400 mg/60 mg – Test product), or 2 soft capsules with liquid content of SpaltGrippal® (200 mg/30 mg - Reference product) under fasting conditions. For the evaluation of bioequivalence, the 90% CI of log-transformed values were calculated for the ratios Test vs Reference for AUC(0-t) and Cmax of ibuprofen (racemic) and (1S,2S)-pseudoephedrine and then compared to the corresponding acceptance ranges. Safety and tolerability were assessed during the clinical period and one week after the last dose. Results: Bioequivalence was demonstrated for both Cmax and AUC(0-t) of pseudoephedrine, as well as for the total exposure of ibuprofen, while the Cmax of ibuprofen slightly exceeded the upper acceptance limit by approximately 6%. For both actives, Tmax was lower with the granule’s formulation. The overall safety and tolerability of the study medications were identical Conclusions: Although the bioequivalence criteria between Test and Reference product were not completely met, the new formulation of ibuprofen/pseudoephedrine granules for oral solution is able to provide a therapeutic equivalence to conventional solid forms, ensuring a more convenient administration, faster onset of analgesia for the patient without altering its total exposure.