The use of floating drug-delivery systems is one method that is used to achieve prolonged gastric residence times. We developed a novel, multiple-unit, floating drug-delivery system of microspheres with microballoons inside from xanthan gum (XG) and gelatin (GA) by a water-in-oil method. With theophylline as the model drug, four formulations (FI-FIV) with different ratios of the two polymers were prepared. The size distribution, drug-encapsulation efficiency, floating behavior, release characteristics, and morphological properties were investigated. The ratio of the two polymers influenced the size distribution, encapsulation efficiency, and drug release appreciably. With increasing amounts of GA, the percentage yield of the floating microspheres and the drug-encapsulation efficiency decreased from 100 and 84.5% to 31 and 56.2%, respectively. The drug-release rate also decreased with increasing GA content, which was attributed to an increase in the crosslinking extent. An initial burst was observed, and after that, the drug was released slowly by a near-zero-order pattern, which was attributed to the low solubility of theophylline and the possible complexes formed by XG and GA in the simulated gastric fluid (pH 1.2). (C) 2004 Wiley Periodicals, Inc.