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

ABSTRACT

The objectives of this study were to assess the bioavailability of an optimized mephenamic acid [MFA] microspheres [test] against a Ponstan[R] capsule [reference] in healthy volunteers, and to establish a correlation with in vitro parameters. 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 infinity [AUC[0-infinity]] were calculated from the plasma drug concentration-time data. 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 micro g/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. 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-infinity], 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