Background: Frequent administration caused by short half-life and low bioavailability due
to poor solubility and low dissolution rate limit the further application of poorly water-soluble nimodipine,
although several new indications have been developed. To overcome these shortcomings,
sophisticated technologies had to be used since the dose of nimodipine was not too low and the addition
of solubilizers could not resolve the problem of poor release.
Objective: The purpose of this study was to obtain sustained and complete release of nimodipine with
a simple and easily industrialized technology.
Methods: The expandable monolithic osmotic pump tablets containing nimodipine combined with
poloxamer 188 and carboxymethylcellulose sodium were prepared. The factors affecting drug release
including the amount of solubilizing agent, expanding agent, retarding agent in core tablet and porogenic
agent in semipermeable film were optimized. The release behavior was investigated both in vitro
and in beagle dogs.
Results: It was proved that the anticipant release of nimodipine could be realized in vitro. The sustained
and complete release of nimodipine was also realized in beagles because the mean residence
time of nimodipine from the osmotic pump system was longer and Cmax was lower than those from the
sustained-release tablets in market while there was no difference in AUC(0-t) of the monolithic osmotic
pump tablets and the sustained release tablets in market.
Conclusion: It was reasonable to believe that the sustained and complete release of poorly watersoluble
nimodipine could be realized by using simple expandable monolithic osmotic pump technology
combined with surfactant.