In Vivo Evaluation of Two Novel Controlled-Release Nitrendipine Formulations

Abstract

The objective of this work is to assess two novel controlled-release nitrendipine formulations, i.e., sustained-release nitrendipine microspheres having solid dispersion structure and a novel pH-dependent gradient-release delivery system for nitrendipine in healthy male volunteers, which were prepared by current authors. Domestic commercial nitrendipine tablets and Baypress™ nitrendipine tablets were employed as reference formulations. In a randomized, single-dose, fasting-state, crossover study design with a 1-week washout period, each subject received a 40-mg nitrendipine formulation. Plasma samples were collected over a 25-hour period after oral administration and were analyzed by a validated method using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined using a noncompartmental analysis. The results provided evidence that the time to maximum plasma concentration of two novel controlled-release nitrendipine formulations were statistically significant prolonged in comparison with that of Baypress™ nitrendipine tablets. The relative bioavailabilities of test formulations were intensively improved compared with the domestic nitrendipine tablets, while the ratio is in a range of 80–120% in comparison with Baypress™ nitrendipine tablets. It is concluded that the two types of controlled-release systems are feasible for improving the dissolution rate of nitrendipine and obtaining a long-acting in vivo as well.

Key Words:

• Nitrendipine
• Pharmacokinetics
• Relative bioavailability
• Controlled-release formulation