Inclusion Complex of SBE7-β-CD with TMP: Preparation, Characterization and Molecular Simulation / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare inclusion complex of SBE7-β-CD with trimethoprim(TMP) and optimize the preparation process, to evaluate the products by structural characterization and molecular simulation. METHODS: The TMP/SBE7-β-CD inclusion complex was prepared by the ultrasound-freeze-dry method and the preparation process was optimized by Box-Behnken Design-response surface method(BBD-RSM). Inclusion complex was characterized by FT-IR, DSC, XRPD and 1H-NMR. Molecular docking method was used to simulate 3-dimensional conformations of the inclusion complex and the binding energy was calculated. The dissolution and stability were tested. RESULTS: The optimum conditions of TMP/SBE7-β-CD inclusion complex were temperature(52 ℃), time(45 min), and the ratio of SBE7-β-CD and TMP(mol/mol, 1.7∶1). All characterizations(FT-IR, DSC, XRPD and 1H-NMR) indicated the formation of TMP/SBE7-β-CD inclusion complex. The best 3-dimensional docking conformation was consistent with the characterizations, and the binding energy was -9.015 kcal·mol-1. The TMP dissolution rate of the inclusion complex increased significantly, the hygroscopicity is strong. CONCLUSION: The preparation process of TMP/SBE7-β-CD inclusion complex optimized by BBD-RSM is reasonable and feasible. The characterizations of inclusion complex are reliable. The molecular simulation is corresponded to the characterized results and provided reliable theoretical basis for inclusion experiments.