目的 研究Emprove 低内毒素蔗糖、Emprove 低内毒素甘露醇、Emprove 低内毒素甘氨酸3 种不同类型冻干保护剂对硼替佐米冻干粉针性能的影响.方法 以硼替佐米冻干粉针和空白冻干粉针的外观和复溶效果为指标,考察预冻时间、冻干保护剂用量、冻干时间、叔丁醇体积分数的影响.比较了硼替佐米冻干粉针和空白冻干粉针的含水量、pH 值和硼替佐米的质量分数.结果 3 种冻干保护剂均能在适宜条件下制备硼替佐米冻干粉针,以Emprove 低内毒素蔗糖为冻干保护剂,预冻时间24 h,用量15%,冻干时间15 h,叔丁醇体积分数40%;以Emprove 低内毒素甘露醇为冻干保护剂,预冻时间6 h,用量4%,冻干时间6 h,叔丁醇体积分数40%;以Emprove 低内毒素甘氨酸为冻干保护剂,预冻时间6 h,用量4%,冻干时间6 h,叔丁醇体积分数20%;所得产品饱满、平整,完全复溶.冻干后含水量< 5%,pH 值和硼替佐米的质量分数变化不显著.结论 Emprove 低内毒素蔗糖、Emprove 低内毒素甘露醇、Emprove 低内毒素甘氨酸均适合用作硼替佐米冻干粉针剂制备的冻干保护剂,实验为难溶性药物冻干制剂的制备提供了参考.

Objective To study the effects of three types of freeze-drying powder protective agents (Emprove low endotoxin sucrose, Emprove low endotoxin mannitol, and Emprove low endotoxin glycine) on properties of Bortezomib Freeze-dried Powder. Methods Appearance and re-dissolving performance of Bortezomib Freeze-dried Powder and its blank were used as indexes, and time of pre-freezing, dosage of lyoprotectants, time of freeze-drying, and tert-butyl alcohol concentration were studied. At the same time, moisture content, pH value, and change of bortezomib content were determined. Results All the three freeze-drying powder protective agents could be used as lyoprotectants for Bortezomib Freeze-dried Powder in suitable conditions. The optimal conditions were as following: Emprove low endotoxin sucrose was used as freeze-drying powder protective agent, time of pre-freezing was 24 h, dosage of lyoprotectants was 15%, time of freeze-drying was 15 h, and tert-butyl alcohol concentration was 40%; Emprove low endotoxin mannitol was used as freeze-drying powder protective agent, time of pre-freezing was 6 h, dosage of lyoprotectants was 4%, time of freeze-drying was 6 h, and tert-butyl alcohol concentration was 40%; Emprove low endotoxin glycine was used as freeze-drying powder protective agent, time of pre-freezing was 6 h, dosage of lyoprotectants was 4%, time of freeze-drying was 6 h, and tert-butyl alcohol concentration was 20%. The products were full, smooth, and complete re-dissolving performance. There were no significant changes of pH value, and bortezomib content, and moisture content was below 5% after freeze-drying. Conclusion Emprove low endotoxin sucrose, Emprove low endotoxin mannitol, and Emprove low endotoxin glycine are all suitable for the preparation of Bortezomib Freeze-dried Powder, which can provide references on freeze-drying preparation of insoluble drugs.