生物学的同等性とバイオアベイラビリティのジャーナル

概要

Comparative Bioavailability Assessment of Newly Developed Flurbiprofen Matrix Tablets and Froben SR® Tablets in Healthy Pakistani Volunteers

Shahana Khattak, Farnaz Malik, Abdul Hameed, Safia Ahmad, Muhammad Rizwan, Humayun Riaz and Shahzad Hussain

Background: Flurbiprofen is a non-selective cyclo-oxygenase inhibitor, member of series of alkanoic acid derivatives, has anti-inflammatory, analgesic activity. Also used to treat gout, osteoarthritis, rheumatoid arthritis and is effective in inhibiting surgically induced miosis in human eyes while cataract extraction. Oral sustained release formulation as a novel matrix system of flurbiprofen tablets were prepared using Carboxy methylcellulose as release retardant. Objective: The aim of present study was comparative bioavailability assessment of newly developed flurbiprofen matrix tablets for sustained delivery, with commercially available Froben SR. Methods: Randomized, open-label, 2-periods, cross-over study conducted on 24 male healthy volunteers in Pakistan. Small batch of flurbiprofen matrix tablets were manufactured and evaluated according to Pharmacopoeial specifications. Each volunteer received a 200-mg tablet of the test and reference formulations, separated by a 7-day washout period. Blood samples were obtained before dosing 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours after drug administration. Safety monitoring was performed which includes adverse events. Plasma concentrations of the 2 formulations were determined, and pharmacokinetic parameters were compared using noncompartmental analysis. In-vivo disposition kinetics was evaluated using single dose, cross over, complete two period of treatment design in twenty four healthy male human volunteers; the drug was assayed in plasma using HPLC-UV detection, and results were compared. Various pharmacokinetic parameters (Cmax, Tmax, area under the curve [AUC0-24], mean residence time) and relative bioavailability were compared. Results: No significant differences were found for Cmax, Tmax,AUC and other parameters. The rate and extent of drug release from matrix tablets was not significantly different from commercially available Froben SR tablets. An in vivo result indicates prolonged blood levels with delayed peak and comparable bioavailability. Conclusions: The matrix tablets could also provide, sustained, gastrointestinal environmentalindependent release that may result in an improved therapeutic efficacy.