In-vivo and in-vitro evaluations of a modified-release oral dosage form of nifedipine by hybridization of hydroxypropyl-beta-cyclodextrin and hydroxypropylcelluloses in dogs.
To maintain a suitable blood level of nifedipine for a long period of time, double-layer tablets consisting of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 3% nonionic surfactant (HCO-60) as a fast-release portion and hydroxypropylcelluloses (HPCs) with different viscosity grades (low, medium and high) as a slow-release portion were prepared, and their in-vitro and in-vivo release behaviours were investigated. Among the seven formulations, the tablet having the mean dissolution time of 0.8-1.3 h gave prolonged plasma nifedipine levels without decrease of AUC after oral administration to dogs. Consequently, the double-layer tablet consisting of HP-beta-CyD with 3% HCO-60/(HPC-low:HPC-medium) in a weight ratio 1/(1.5:1.5) was selected as an appropriate modified-release formulation because it elicited almost comparable retarding effects with superior oral bioavailability compared with those of a commercially available slow-release nifedipine product.
Wang
Z
Z
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Hirayama
F
F
Uekama
K
K
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives*; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004285:Dogs; D007408:Intestinal Absorption; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002482:Cellulose; C008079:hydroxypropylcellulose; D009543:Nifedipine