Bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a fixed-combination syrup versus an oral reference product

Abstract

Objectives The primary objective of this study was to compare the bioavailability of paracetamol, phenylephrine hydrochoride and guaifenesin in a new oral syrup with an established oral reference product. The secondary objective was to compare the safety of the new syrup and the reference product. Methods This was a single-centre, open-label, randomized, reference-replicated, crossover study. Healthy adult volunteers received one dose of syrup and two separate doses of a reference oral liquid formulation in a randomized sequence over three study periods, with a washout interval of ≥7 days between study periods. Blood samples were taken regularly postdose and analysed for paracetamol, phenylephrine hydrochoride and guaifenesin concentrations; adverse events were recorded. Results This study enrolled 45 subjects. For paracetamol and guaifenesin, the syrup and reference product were considered to be bioequivalent. Bioequivalence was not shown for phenylephrine hydrochoride. All adverse events were mild or moderate, most of which were considered formulation related. Conclusions The syrup did not reach bioequivalence with the reference product, as bioequivalence could not be shown for phenylephrine hydrochoride. This may be due to differences in the excipients between the two products. Both the syrup and the reference product had a good safety profile and were well tolerated.