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

Abstract

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.

Kinetics of drug release from drug carrier of polymer/TiO2 nanotubes composite—pH dependent study

“…The degree of ionization of a drug is calculated by eq. and …”

Correlation between in vitro dissolution profiles from enteric-coated dosage forms and in vivo absorption in rats for high-solubility and high-permeability model drugs

“…Numerous studies on the IVIVC for immediate‐release solid oral dosage forms have been reported 9–16. Many researchers have also investigated the IVIVC for sustained‐release solid oral dosage forms17–24; however, there have been only a few reports on the correlation between in vitro dissolution profiles of drugs from enteric‐coated dosage forms and in vivo drug absorption 25–27. A better understanding of IVIVC for enteric‐coated dosage forms would be helpful in assessing in vivo bioavailability and bioequivalence among various formulations in the process of drug development.…”