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

Abstract

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_max and AUC_0-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 C_max (90.71-101.77) and AUC_0-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 T_max (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_max and AUC_0-t 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_0-t and C_max. 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.

Keywords: bioequivalence; enantiomer; ibuprofen; nonsteroidal anti-inflammatory drug; orodispersible tablet; pain management.