Preparation and In Vitro Evaluation of a Microballoon Delivery System for Theophylline

Abstract

A multiple-unit oral floating system was prepared using the emulsification-solvent diffusion method to prolong the gastric emptying time of theophylline. For this purpose, theophylline, ethyl cellulose and dibutyl phthalate were dissolved in an ethanol/dichloromethane mixture, added to 0.1 M HCl containing NaCl (20%) or saturated theophylline and/or different concentrations of polysorbate 80 and polyvinyl alcohol. The mixture was stirred at different speeds for 3 h. The resulting microspheres were separated from the solution by filtration. Physical characteristics, including the shape and size distribution, floating capability, drug loading and drug release of the resulting theophylline microspheres were investigated. The prepared microspheres tended to float over the simulated gastric medium for over 12 h. Addition of NaCl (20%) to the aqueous phase increased the drug loading of microballoons. The mean geometric diameter of microspheres decreased, as the stirring speed rate or the polysorbate 80 concentration were increased. Microballoons prepared at higher stirring rates released their drug content faster. Also, it is concluded that particle size and floating capability of microballoons could be adjusted by altering the stirring rate during microencapsulation.