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

PURPOSE

This study aimed to assess the comparative bioavailability between ibuprofen acid orodispersible tablets (Test product) and ibuprofen acid oral tablets (Reference product).

METHODS

This 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.

FINDINGS

After a single-dose administration of ibuprofen acid oral tablets (2 × 200 mg), the total ibuprofen C and AUC (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 C (90.71-101.77) and AUC (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 T (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 C and AUC LS mean Test/Reference ratio 90% CI for both ibuprofen S(+) and R(-) enantiomers contained entirely within the predetermined 80%-125.00% limits.

IMPLICATIONS

This study found that ibuprofen acid 200 mg orodispersible tablets and ibuprofen acid 200 mg tablets met the regulatory criteria for bioequivalence for AUC and C. 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.