Preliminary bioequivalence testing of two nicardipine HCl sustained-release formulations with in vitro/in vivo correlations.

A new nicardipine HCl oral sustained-release dosage form was evaluated for bioequivalence in comparison with a reference product, Cardene SR. Six healthy subjects, fasted overnight, were enrolled in a single-dose, open-label, randomized, and two-way crossover study. Blood samples were collected over a 12 hour period, and nicardipine plasma concentrations analyzed from plasma. Pharmacokinetic parameters, including Cmax, t(max), and AUC, were obtained from drug plasma concentration-time curves and pharmacokinetic analysis conducted using WinNonlin. The two one-sided t-test was applied in statistical analysis for comparison of the pharmacokinetic parameters between the two products. There was no convincing evidence that nicardipine HCl test product and Cardene SR were bioequivalent. Amounts of nicardipine HCl release in vivo was mathematically obtained by deconvoluting plasma concentration-time data after oral administration using IV bolus injection data as a reference. Plots of percentages of drug release in vitro against those in vivo illustrated triphasic curves. After the in vitro time scale was corrected and then plotted against in vivo data, plots provided a polynomial relationship (R2 of 0.9920 and 0.9954). The in vitro/in vivo correlation may be useful in reformulating this particular test formulation to obtain a product with an in vivo release rate identical to Cardene SR.

RCT Entities:   Population Interventions Outcomes