Design and in-vitro evaluation of a modified-release oral dosage form of nifedipine by hybridization of hydroxypropyl-beta-cyclodextrin and hydroxypropylcellulose.
To modify the release rate of nifedipine, a potent calcium channel antagonist, a double-layer tablet was designed, anticipating a more balanced oral bioavailability and a prolonged efficacy than the simple plain tablet. Amorphous nifedipine powders prepared by spray-drying with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and nonionic surfactant HCO-60 were employed as a fast-release portion to attain an initial rapid dissolution of nifedipine. Hydroxypropylcelluloses (HPCs) with different viscosity grades (type L, M, and H) were used for a slow-release portion to provide an appropriate sustained-release. Taking into account the physiological conditions of the gastrointestinal tract (pH and motility), an optimal formulation of the double-layer tablet was obtained by changing the mixing ratios of each component. For example, the tablet consisting of HP-beta-CyD with 3% HCO-60/(HPC-L:HPC-M) in the weight ratio 1/2(1:1) provided a sufficient slow release of the drug over a wide pH region following an initial rapid dissolution. The release of nifedipine from the double-layer tablets was little affected by pH of the medium and rotation speed of paddle after accelerated storage conditions (60 degrees C, 75% r.h.). The present results suggest that a combination of HP-beta-CyD, HCO-60 and HPCs can serve as a modified-release carrier for poorly water-soluble nifedipine.
Wang
Z
Z
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Horikawa
T
T
Hirayama
F
F
Uekama
K
K
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D015195:Drug Design; D009543:Nifedipine / Q000008:administration & dosage* / Q000737:chemistry*; D011208:Powders; D012995:Solubility; D013607:Tablets; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D011208:Powders; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002482:Cellulose; C008079:hydroxypropylcellulose; D009543:Nifedipine