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