目的 研究Emprove 低內(nèi)毒素蔗糖、Emprove 低內(nèi)毒素甘露醇、Emprove 低內(nèi)毒素甘氨酸3 種不同類型凍干保護劑對硼替佐米凍干粉針性能的影響.方法 以硼替佐米凍干粉針和空白凍干粉針的外觀和復溶效果為指標,考察預凍時間、凍干保護劑用量、凍干時間、叔丁醇體積分數(shù)的影響.比較了硼替佐米凍干粉針和空白凍干粉針的含水量、pH 值和硼替佐米的質(zhì)量分數(shù).結(jié)果 3 種凍干保護劑均能在適宜條件下制備硼替佐米凍干粉針,以Emprove 低內(nèi)毒素蔗糖為凍干保護劑,預凍時間24 h,用量15%,凍干時間15 h,叔丁醇體積分數(shù)40%;以Emprove 低內(nèi)毒素甘露醇為凍干保護劑,預凍時間6 h,用量4%,凍干時間6 h,叔丁醇體積分數(shù)40%;以Emprove 低內(nèi)毒素甘氨酸為凍干保護劑,預凍時間6 h,用量4%,凍干時間6 h,叔丁醇體積分數(shù)20%;所得產(chǎn)品飽滿、平整,完全復溶.凍干后含水量< 5%,pH 值和硼替佐米的質(zhì)量分數(shù)變化不顯著.結(jié)論 Emprove 低內(nèi)毒素蔗糖、Emprove 低內(nèi)毒素甘露醇、Emprove 低內(nèi)毒素甘氨酸均適合用作硼替佐米凍干粉針劑制備的凍干保護劑,實驗為難溶性藥物凍干制劑的制備提供了參考.

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.