OBJECTIVE  To study the bioequivalence of ibuprofen granules produced by Zhejiang CONBA Pharmaceutical Co., Ltd. and Brufen^® (20% ibuprofen granules) produced by Kaken Pharmaceutical Co., Ltd. under fasting/fed conditions in healthy adult volunteers. To compare and summarize the design and results of bioequivalence tests for ibuprofen granules that have passed the consistency evaluation of quality and efficacy in domestic generic drugs.

METHODS  Forty-eight healthy subjects were randomly divided into fasting and fed groups. Twenty-four subjects in the fasting/fed group were given two ibuprofen granules orally in a randomized, open, double-cycle, double-crossover, single-dose trial design under fasting/fed conditions. Then the plasma concentration of ibuprofen was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin 7.0 to evaluate the bioequivalence between the test preparation and the reference preparationt. Conducted a comparative analysis and summary of the bioequivalence test design and results for ibuprofen granules from seven additional manufacturers that have been approved through consistency evaluation by the Center for Drug Evaluation of the National Medical Products Administration, estimate the coefficient of variation in key pharmacokinetic parameters within individuals, and analyze from aspects such as test type, sample size, reference preparation, and food impact.

RESULTS  In the fasting group, the 90% confidence intervals of the geometric mean ratio of C_max, AUC_0-t and AUC_0-∞ were 85.84%−98.57%(C_max), 97.75%−101.18%(AUC_0-t), and 97.73%−101.32%(AUC_0-∞) for the test preparations and reference preparations. In the fed group, the 90% confidence intervals of the geometric mean ratio of C_max, AUC_0-t and AUC_0-∞ were 91.72%−107.26%(C_max), 95.70%−100.21%(AUC_0-t), and 95.76%−100.16%(AUC_0-∞) for the test preparations and reference preparations. The corresponding values were also within the range of 80.00%−125.00%. Meanwhile, in comparison to bioequivalence results for other companies' ibuprofen granules , both the reference and test formulations were affected by fed conditions, indicating a decrease in C_max levels after fed. Specifically, there was a trend of decreased C_max levels, which on average decreases by about 50%, while the impact on AUC_0-t and AUC_0-∞ was not significant, decreasing by about 10%.

CONCLUSION  The test formulation and reference preparation of ibuprofen granules are found to be bioequivalent in healthy subjects under fasting and fed conditions. The analysis and recommendations for the bioequivalence testing of ibuprofen granules provides in this study serve as a reference for future bioequivalence studies of ibuprofen granules.