卡巴他赛纳米脂质体冻干工艺的考察

nvestigation on the Lyophilization Technology of Cabazitaxel Nanoliposomes

为了提高贮存稳定性、降低乙醇残留量,将卡巴他赛纳米脂质体制备成冻干注射剂,并对冻干工艺进行了研究与优化。以冻干产品的外观、主药含量、包封率、水分含量、乙醇残留量、贮存稳定性为评价指标,考察了冻干保护剂(蔗糖)用量、料液装量、预冻速度、干燥温度对产品质量的影响。结果表明,蔗糖与磷脂的质量比为5.0时较佳;脂质体中卡巴他赛的质量浓度为2 mg/mL;装量为每瓶20 mg;西林瓶选用20或30 mL 2个规格。优化冻干工艺参数为:预冻温度–40℃,隔板降温时间90 min,–40℃时保温5 h;一次干燥温度–15℃,一次干燥时间14 h;二次干燥温度28℃,二次干燥时间28 h;冻干全程总耗时48.83 h;干燥过程采用阶段式升温方式。优化冻干工艺的冻干周期大幅缩短,所得冻干制剂贮存稳定性良好。

In order to improve storage stability and reduce residual ethanol,cabazitaxel nanoliposomes were prepared into lyophilized injection,and the lyophilization process was investigated and optimized.Taking the appearance,main drug content,encapsulation efficiency,moisture content,residual ethanol and the storage stability of lyophilized powder as evaluation indicators,the effects of dosage of lyophilized protective agent(sucrose),the filling volume of feed liquid,pre-freezing speed and drying temperature on the quality of the lyophilized injection were investigated.The results showed that the optimum mass ratio of sucrose to phospholipid was 5.0;the mass concentration of cabazitaxel in the nanoliposomes was 2 mg/mL;specification was 20 mg per bottle;xilin bottle specification was 20 or 30 mL.The optimal lyophilization process parameters were as follows:the pre-freezing temperature was–40℃,the shelf cooling time was 90 min,then holding at–40℃for 5 h;the primary drying was conducted at–15℃for 14 h;the secondary drying was conducted at 28℃for 28 h;the total lyophilization time was 48.83 h;a stepwise heating mode was adopted in the whole drying process.The lyophilization cycle of optimal process was greatly shortened,and the obtained lyophilized injection had good storage stability.