In vitro/in vivo Correlation of Fast Release Mephenamic Acid Microspheres in Humans

Abstract

Objectives: The objectives of this study were to assess the bioavailability of an optimized mephenamic acid (MFA) microspheres (test) against a Ponstan® capsule (reference) in healthy volunteers, and to establish a correlation with in vitro parameters. Subjects andMethods: Four subjects received the test and reference (250 mg MFA each) in a randomized crossover design, separated by a 1-week washout period. The drug was analyzed in plasma by a specific high-performance liquid chromatographic method. The relevant pharmacokinetic parameters [maximum plasma concentration (C_max), time of peak concentration (T_max), area under plasma concentration-time curves from 0 to 12 h (AUC_0–12) and area under plasma concentration-time curves from zero to ∞ (AUC_0–∞)] were calculated from the plasma drug concentration-time data. Results: The test product exhibited faster absorption (T_max of 1.87 ± 0.482 vs. 2.14 ± 0.20 h; C_max of 5.91 ± 0.604 vs. 3.58 ± 0.671 µg/ml) when compared to the reference. The relative bioavailability of the test compared to the reference capsule was 172%. Good correlations were established between the in vitro 90% dissolution (T90) and each of the AUC_0–12 and T_max, as well as between the percentage of drug released and plasma concentrations. Conclusion: The formulation of MFA microsphere with polyethylene glycol improved the dissolution rate and bioavailability of MFA, as evidenced by a higher C_max, AUC_0–12 and AUC_0–∞, and shorter T_max values. Good correlations between T90 and both AUC_0–12 and T_max as well as between the percentage of drug released and plasma concentrations were achieved.