Response surface methodology to optimize the preparation of tosufloxacin tosylate/hydroxypropyl-β-cyclodextrin inclusion complex by supercritical antisolvent process

Response surface methodology was designed to optimize the process parameters for the preparation of the tosufloxacin tosylate/hydroxypropyl-beta-cyclodextrin inclusion complex by supercritical antisolvent method (SAS). The optimum inclusion conditions were temperature 45 degrees C, pressure 12 MPa, molar ratio 1:1, and mixed solvent 20% DCM, in which case the inclusion efficiency was 15.18%. Three-dimensional response plots revealed that molar ratios and mixed solvents have a more pronounced effect on inclusion efficiency than temperature and pressure. Characterization results of SEM, EDX, PXRD and FT-IR confirmed that the inclusion complex was successfully prepared, and the inclusion sites of all inclusion complexes were located on the phenyl ring A, pyrrolidine and naphthyridine ring protons. The dissolution of the inclusion complex in the pH 6.8 buffer solution was up to 68.14%, indicating that the inclusion complex prepared by the SAS process could significantly improve the dissolution of tosufloxacin tosylate. (C) 2019 Elsevier B.V. All rights reserved.