Bioequivalence study of three ibuprofen formulations after single dose administration in healthy volunteers

Abstract

Background: This phase I study was designed to determine the bioavailability and bioequivalence of 400 mg Eudorlin extra* (Ibuprofen) in comparison to two reference formulations (400 mg Nurofen forte and 400 mg Migränin after single dose administration under fasting conditions in healthy subjects. Therefore the design of a randomized, open label, multiple sequence cross-over study with a wash-out period of 7-10 days was used.

Results: AUC(0-t)(last) and AUC(0-infinity) (90%CI) were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the EMEA. Cmax (90%CI) was within the EMEA acceptance range of 75 to 133%. Detailed analyses showed that Cmax of Eudorlin extra was higher than that of Nurofen forte (36.62 vs. 32.92 microg/ml; p = 0.0014) and that of Migränin (35.94 vs. 30.87 microg/ml; p < 0.0001). The time to maximum plasma concentration (tmax) was shorter with Eudorlin extra than with Nurofen forte (1.14 vs. 1.82 h; p < 0.0001) and Migränin (1.13 vs. 1.78 h; p = 0.0031). Only 1 patient experienced an adverse with possible relation to the study drug taking Migränin.

Conclusion: It is concluded that Eudorlin extra is bioequivalent to the two reference preparations Nurofen forte and Migränin for both, the extent and the rate of absorption, after single dose administration in healthy volunteers according to the guidance of the EMEA. Within this frame, peak plasma concentrations are however reached earlier and peaks are higher compared to the reference products. * Eudorlin extra may have different brand names in different countries.

Figures

Figure 1

Results of dissolution testing. Dissolution testing of 400 mg tablets Eudorlin® Extra (Test formulation, in red) versus 400 mg Nurofen® Forte (Reference formulation 1, black) and 400 mg Migränin® (Reference formulation 2, broken black).

Figure 2

Plasma concentration time curve Eudorlin® vs. Nurofen®. Geometric mean time curve for plasma concentration of ibuprofen; cross-over Eudorlin® extra – Nurofen® forte (Pharmacokinetic population; N = 60).

Figure 3

Plasma concentration time curve Eudorlin® vs. Migränin®. Geometric mean time curve for plasma concentration of ibuprofen; cross-over Eudorlin® extra – Migränin® (Pharmacokinetic population; N = 60).

Figure 4

Allocation of subjects to the appropriate sequence groups during the study. S: Sequence groups; A: subjects receiving drug A (Nurofen® forte), B: subjects receiving drug B (Migränin®, E: subjects receiving Eudorlin® extra.