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(R) SR. Six h ealthy subjects, fasted overnight, were enrolled in a single-dose, open-lab el, randomized, and two-way crossover study. Blood samples were collected o ver a 12 hour period, and nicardipine plasma concentrations analyzed from p lasma. Pharmacokinetic parameters, including C-max, t(max), and AUC, were o btained from drug plasma concentration-time curves and pharmacokinetic anal ysis conducted using WinNonlin(R). The two one-sided t-test was applied in statistical analysis for comparison of the pharmacokinetic parameters betwe en 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 concent ration-time data after oral administration using IV bolus injection data as a reference. Plots of percentages of drug release in vitro against those i n vivo illustrated triphasic curves. After the in vitro time scale was corr ected and then plotted against in vivo data, plots provided a polynomial re lationship (R-2 of 0.9920 and 0.9954). The in vitro/in vivo correlation may be useful in reformulating this particular test formulation to obtain a pr oduct with an in vivo release rate identical to Cardene(R) SR.