Time-release compression-coated core tablet containing nifedipine for chronopharmacotherapy

Abstract

Compression-coated time-release tablets (CC tablets) containing nifedipine, dihydropyridine Ca channel blocker, in the core tablet were prepared by dry coating with different polyethylene oxide-polyethylene glycol mixtures. Each formulation showed a clear lag period before nifedipine release initiation, followed by sustained drug release lasting up to 24 h. The lag time of nifedipine release increased as the amount of polyethylene oxide in the outer layer increased. To investigate the applicability of such CC-tablets for chronopharmacotherapy, the pharmacokinetics of CC-1 and CC-2 tablets, with different in vitro lag times before drug release, were compared with the pharmacokinetics of a sustained-release (SR) tablet in dogs. The times of first nifedipine appearance (TFA) in plasma were 0.7 ± 0.3 h for SR, 2.5 ± 1.2 h for CC-1, and 5.3 ± 1.0 h for CC-2. These data show a significant difference in in vivo lag time ( P < 0.01) among the three formulations that correlates with the in vitro lag times. Thus, the in vivo lag time could be predicted from the in vitro lag time. Additionally, higher plasma nifedipine concentrations were observed at 8 h after administration of the CC-2 than that observed for the SR-tablet. These results indicate that a CC-tablet with a lag time before drug release is a potentially useful formulation for chronopharmacotherapy that can control the time and duration of plasma drug concentration better than existing SR technologies.