Comparative studies of bioavailability of ibuprofen tablets commercially available in Thailand

Abstract

This investigation was to assess the bioequivalence of the local manufactured brands ofR200 mg ibuprofen sugar coated tablets relative to the original brand, Brufen. These tablets were evaluated both in vitro and in vivo. The in vitro studies included both disintegration time and dissolution rate. The disintegration times of ibuprofen tablets were ranged from nine minutes to more than five hours. Of the 15 brands studied, tablets of 13 brands were able to disintegrate within one hour, tablets of one brand had wide varied disintegration times ranged from 1.28 to 2.42 hours and tablets of one brand did not disintegrate evenafter they were placed in the medium for over five hours. The dissolution rate constants of these fifteen brands of ibuprofen tablets were ranged from 0.0035 to 0.3310 per minute. The amount of drug dissolved at 30 minutes indicated that five brands met the U.S.P. XXI specification for drug dissolution while seven brands failed to meet the specification and three brands required extra experiments before any conclusion could be made. Five brands of ibuprofen tablets with difference in their dissolution rate constant were selected to study for their bioequivalence in 12 Thai healthy male volunteers ranging in age from 21 to 27 years using a crossover design. After an overnight fasted two tablets, each containing ibuprofen 200 mg, were administered orally. Plasma ibuprofen levels were determined by a specifically high-performance liquid chromatographic method. Individual plasma profile was analyzed using both compartmental and noncompartmental methods. No significant difference (p > 0.05) in the extent of absorption could be observed among .the five brands of ibuprofen studied (except for the brand which its in vitro data showed no disintegration evenafter five hours, no ibuprofen was detected in the plasma of any subjects at any time). However, they differed significantly in terms of their absorption rate (P < 0.05). There were statistically significant correlation between disintegration time and dissolution rate constant, beb1een disintegration time and in vivo absorption rate (p < 0.05) but no significant linear relationship was observed between dissolution rate constant and in vivo absorption rate (p > 0.05). In this study, the mean peak plasma ibuprofen concentration and the time required to reach the peak were ranged from 16.80 to 42.20 pg/ml and 1.29 to 4.75 hours respectively. The elimination half-life of ibuprofen in Thai male was 2.34 hours (2.17- 2.65 hours). These results are quite similar to those previously reported in the foreign literatures.