PREPARATION OF MULTIPLE UNIT HOLLOW MICROSPHERES (MICROBALLOONS) WITH ACRYLIC RESIN CONTAINING TRANILAST AND THEIR DRUG RELEASE CHARACTERISTICS (INVITRO) AND FLOATING BEHAVIOR (INVIVO)

Microballoons with hollow structure were prepared as a novel multi-unit floating device for use in the stomach by the emulsion-solvent diffusion method. As a model drug, tranilast, an oral anti-allergic agent, was embedded in the shell of the microballoon. Tranilast and acrylic polymer, dissolved in an ethanol-dichloromethane mixture, were poured into an aqueous solution of polyvinyl alcohol with stirring to form emulsion droplets. By changing the polymer concentration in the cosolvent and the ratio of ethanol to dichloromethane, it was possible to prepare microballoons with various drug contents. With higher polymer ratios, the internal cavity volume of the microballoon increased and the drug dispersed in the shell of the microballoon became amorphous. The drug release profiles from microballoons exhibited enteric behavior. The release rate was controlled by changing the ratio of polymer to drug in the microballoon. Most of the microballoons were floatable in vitro even testing for 12 h when immersed in aqueous media, owing to their low particle density (less than unity). An in vivo radiographical study proved that microballoons orally administered to humans were dispersed in the upper part of the stomach and retained there for over 3 h against peristaltic action.