Preparation of TM-4000 Sulfobutyl Ether-β-Cyclodextrin Inclusion Complex and Study on Its Solubilization Effect

OBJECTIVE To prepare TM-4000 sulfobutyl ether-β-cyclodextrin inclusion complex and investigate the solubilization effect. METHODS The solubilization effect of sulfobutyl ether-β-cyclodextrin on TM-4000 was preliminary investigated, and the apparent stability constant of the inclusion reaction at different temperatures was determined. The sulfobutyl ether-β-cyclodextrin inclusion complex of TM-4000 was prepared through process screening. A reasonable preparation method and optimal reaction parameters were determined. The sulfobutyl ether-β-cyclodextrin inclusion complex of TM-4000 was prepared, characterized and tested for dissolution. RESULTS In pH 2.0 hydrochloric acid solution, sulfobutyl ether-β-cyclodextrin solubilization effect of TM-4000 was the best. Inclusion compound with a better stability could be prepared through saturated solution method at 50℃ with 60 r·min^-1 stirring in 6 h. The weight ratio of TM-4000 to sulfobutyl ether-β-cyclodextrin was 1:5. The accumulative dissolution of TM-4000-sulfobutyl ether-β-cyclodextrin inclusion complex within 1 h in pH 2.0 medium could reach 80%. CONCLUSION The TM-4000 sulfobutyl ether-β-cyclodextrin inclusion complex prepared in a simple and feasible way can significantly increase the dissolution level of TM-4000.