Comparative Bioavailability Study of a New Orodispersible Formulation of Ibuprofen Versus Two Existing Oral Tablet Formulations in Healthy Male and Female Volunteers

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PurposeThis study aimed to assess the comparative bioavailability between ibuprofen acid orodispersible tablets (Test product) and ibuprofen acid oral tablets (Reference product). MethodsThis was a randomized, single-dose, 3-way crossover, open-label, pharmacokinetic study in 36 healthy male and female volunteers. Blood samples were taken periodically over a 12-h period after dosing to derive total plasma ibuprofen and S(+)/R(−) ibuprofen enantiomer pharmacokinetic parameters; safety profile and tolerability were evaluated throughout the study. FindingsAfter a single-dose administration of ibuprofen acid oral tablets (2 × 200 mg), the total ibuprofen Cmax and AUC0–t (geometric least square [LS] mean) for the Test product was 29.4 μg/mL and 100.6 h/μg/mL, respectively, and for the Reference product it was 30.6 μg/mL and 98.7 h/μg/mL. The geometric LS mean Test/Reference ratio 90% CI for both total ibuprofen Cmax (90.71–101.77) and AUC0-t (98.72–105.23) was contained entirely within the predefined 80.00%–125.00% lower and upper limits; in addition, no statistically significant difference was found in Tmax (P = 0.1819) after fasted administration of the Test and Reference products. There were 4 mild treatment emergent adverse events, considered unrelated to the study drug, reported by 2 volunteers during the study; no serious adverse events, no suspected unexpected serious adverse events. and no clinically significant changes in laboratory safety, vital signs, or 12-lead ECG measurements were reported. The enantiomer-specific analysis mirrored that of total ibuprofen, with the Cmax and AUC0–t LS mean Test/Reference ratio 90% CI for both ibuprofen S(+) and R(−) enantiomers contained entirely within the predetermined 80%–125.00% limits. ImplicationsThis study found that ibuprofen acid 200 mg orodispersible tablets and ibuprofen acid 200 mg tablets met the regulatory criteria for bioequivalence for AUC0–t and Cmax. Post hoc analysis of ibuprofen both S(+) and R(−) enantiomers mirrored the findings for total ibuprofen. All investigational products were found to be well tolerated. Clinicaltrials.gov identifier: NCT03180879.