Optimizing Ibuprofen Dosing: Insights from In vivo and Virtual Pharmacokinetic Trials

Ibuprofen, a common non-steroidal anti-inflammatory drug (NSAID), is widely used in over-the-counter (OTC) settings for pain and fever management, with a maximum daily dose of 1200 mg recommended for non-prescription use. The clinical efficacy of ibuprofen is influenced by formulation-specific differences in drug release profiles. This study systematically compared four ibuprofen formulations: immediate-release (IR) 400 mg tablets, IR 200 mg tablets, lysinate salt equivalent to 400 mg ibuprofen, and a novel bi-layer tablet integrating immediate- and sustained-release (IR/SR) components. Both, in vivo pharmacokinetic (PK) data and physiologically based PK modeling were employed to evaluate absorption kinetics, plasma concentration-time profiles, and therapeutic duration. Plasma concentration thresholds of 6.8 µg/mL and 10.1 µg/mL were used to assess onset and duration of action. The IR/SR 400 mg bi-layer tablet maintained plasma concentrations above these thresholds for eight hours, extending therapeutic coverage by 2–3.5 hours compared to other IR formulations. Virtual PK simulations indicated that only IR 200 mg (six doses/day) and IR/SR 400 mg (three doses/day) regimens sustained therapeutic levels over 24 hours without surpassing OTC limits. The reduced dosing frequency and prolonged efficacy of the IR/SR formulation support its suitability for providing continuous pain and fever relief.