Development of hollow microspheres as floating controlled-release systems for cardiovascular drugs: Preparation and release characteristics

Hollow microspheres of cellulose acetate loaded with four cardiovascular dr ugs (nifedipine [NFD], nicardapine hydrochloride [NCD], verapamil hydrochlo ride [VRP], and dipyridamole [DIP]) were prepared by a novel solvent diffus ion-evaporation method. The oil-in-water emulsion prepared in an aqueous so lution of 0.05% poly(vinyl alcohol) medium with ethyl acetate, a water-solu ble and less toxic solvent, was used as the dispersing solvent. The yield o f the microspheres was up to 80%. The microspheres had smooth surfaces, wit h free-flowing and good-packing properties. Scanning electron microscopy (S EM) confirmed their hollow structures, with sizes in the range 489-350 mum. The microspheres tended to float over the gastric media for more than 12 h . The drug loaded in hollow microspheres was in an amorphous state, as conf irmed by differential scanning microscopy (DSC). The release of the drugs w as controlled for more than 8 h. The release kinetics followed different tr ansport mechanisms depending on the nature of the drug molecules.