In vitro/in vivo correlation of fast release mephenamic acid microspheres in humans.

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 AND METHODS 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.