Author(s): Wang Z, Horikawa T, Hirayama F, Uekama K
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Abstract 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.
This article was published in J Pharm Pharmacol
and referenced in Journal of Physical Chemistry & Biophysics