Sustained release of nifedipine from granules.

Two kinds of granules were prepared: one with pH-dependent release and the other with pH-independent release. The former was composed of nifedipine, hydroxypropyl methylcellulose phthalate, ethylcellulose, and microcrystalline cellulose, while the latter was composed of nifedipine, hydroxypropyl methylcellulose, ethylcellulose, and corn starch. The effects of the mixing ratios of the polymers and the drug contents in the granules were examined in vitro. In both granules, the release was decreased with the increment of ethylcellulose. These sustained-release granules and the commercial fine granules were orally administered to rabbits. In the plasma levels of nifedipine detected from rabbits orally administered sustained-release granules, a reduced but sustained level was observed. This indicates the sustained release of the drug from the granules in vivo. Furthermore, the plasma profiles of nifedipine indicated that the granules with pH-independent release were superior to that with pH-dependent release with respect to prolonging the effective plasma levels and to minimizing the intersubject variations.