HOLLOW MICROSPHERES FOR USE AS A FLOATING CONTROLLED DRUG DELIVERY SYSTEM IN THE STOMACH

Hollow microspheres (microballoons), loaded with drug in their outer polymer shells, were prepared by a novel emulsion-solvent diffusion method. The ethanol:dichloromethane solution of drug (tranilast or ibuprofen) and an enteric acrylic polymer were poured into an agitated aqueous solution of polyvinyl alcohol that was thermally controlled at 40-degrees-C. The gas phase generated in the dispersed polymer droplet by the evaporation of dichloromethane formed an internal cavity in the microsphere of the polymer with the drug. The drugs incorporated in the solidified shell of the polymer were found to be partially or completely amorphous. The flowability and packability of the resultant microballoons were much improved compared with the raw crystals of drug. The microballoons floated continuously over the surface of acidic dissolution media containing surfactant for > 12 h in vitro. The drug release behavior of the microballoons was characterized as an enteric property, and drug release rates were drastically reduced depending on the polymer concentration at pH 6.8.