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

• Published in: Journal of drug delivery science and technology Vol. 70; p. 103235
• Main Authors: Meng, Saige, Wang, Shuangqing, Piao, Ming Guan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.04.2022
• Subjects: In vitro adhesion; Pharmacokinetics; Release kinetics; Stability tests; Synergistic gastroretentive drug delivery system; Synergistic gastroretentive drug delivery system; EE; Stability tests; Release kinetics; GRDDS; GMO; DL; PVA; In vitro adhesion; Pharmacokinetics; EC; HPMC
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103235

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 (X1), dosage (X2), organic solvent volume (X3) and PVA concentration (X4) as independent variables, and drug loading (Y1), encapsulation rate (Y2), yield rate (Y3) and 8 h floating rate (Y4) 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. [Display omitted] •The furosemide hollow-bioadhesive microspheres were successfully prepared.•The microspheres had excellent floating and bioadhesion properties, realizing the controlled release effect.•The relative bioavailability of furosemide increased by 163.84%.•The safety of microspheres was proved at physiological and tissue levels.