Prescription optimization of gastroretentive furosemide hollow-bioadhesive microspheres via Box-Behnken design: In vitro characterization and in vivo evaluation

The synergistic gastroretentive drug delivery systems are capable of delivering drugs with a narrow absorption window. The purpose of this study is to prepare furosemide hollow-bioadhesive microspheres to improve bioavailability. The emulsion solvent volatilization method was adopted, through Box-Behnken design, with polymer ratio (X 1 ), dosage (X 2 ), organic solvent volume (X 3 ) and PVA concentration (X 4 ) as independent variables, and drug loading (Y 1 ), encapsulation rate (Y 2 ), yield rate (Y 3 ) and 8 h floating rate (Y 4 ) were response variables. The interaction effects of the independent and response variables were explored. The optimized hollow-bioadhesive microspheres showed the in vitro floating rate of 93.33 ± 5.24% for 8 h, the in vitro retention rate of 90.67 ± 3.21%, and the sustained drug release of 93.79 ± 4.90% for 12 h. Compared with the hollow microspheres, the hollow-bioadhesive microspheres significantly increase the retention time in the stomach. The results of Differential Scanning Calorimetry , Fourier Transform InfraRed, and X-ray diffraction showed that furosemide had good biocompatibility with excipients. Compared with commercial tablets, the relative bioavailability of hollow-bioadhesive microspheres was increased by 163.84%, and the long-term therapeutic concentration was maintained. The safety evaluation proved the oral safety of microspheres. In conclusion, the safe and economical furosemide hollow-bioadhesive microsphere is a valuable preparation for development, which can improve clinical application.