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.