In vitro evaluation of floating and drug releasing behaviors of hollow microspheres (microballoons) prepared by the emulsion solvent diffusion method.

Hollow microspheres (microballoons) floatable in JPX III No.1 solution were developed as a dosage form characterized by excellent buoyant properties in the stomach. Microballoons were prepared by the emulsion solvent diffusion method utilizing enteric acrylic polymers codissolved with drug in a mixture of dichloromethane and ethanol. The release properties of five different drugs exhibiting distinct water solubilities (aspirin, salicylic acid, ethoxybenzamide, indomethacin and riboflavin) entrapped within microballoons were investigated. Buoyancy of the microballoons decreased with increasing drug release rate. In the case of aspirin, salicylic acid and ethoxybenzamide, the drug release profiles of microballoons proved a linear relationships by Higuchi plotting. However, indomethacin and riboflavin release profiles did not follow the Higuchi equation. When the loading amount of riboflavin was higher than the solubility in the mixture of dichloromethane and ethanol, the drug release profiles of the microballoons displayed an initial burst release. The insoluble riboflavin in the mixture of dichloromethane and ethanol adsorbed on to the microballoon surface in the crystal state. Such riboflavin crystals were released preferentially at the initial stage of the release test, which was attributable to the initial burst. In addition, by incorporating a polymer such as hydroxypropylmethylcellulose within the shell of microballoons, the release rate of riboflavin from the microballoons could be controlled while maintaining high buoyancy.