注射用A型肉毒毒素顶空氧含量与水分关系的探讨

The investigation of the relationship between headspace oxygen content and water content of botulinum toxin type A for injection

目的 以2种规格(0.1 mL分装量和0.5 mL分装量)的注射用A型肉毒毒素(botulinum toxin type A for injection)为例,对顶空氧含量与水分含量关系进行探讨。方法 将0.1 mL制品分别于(25±2)℃、相对湿度60%±5%加速条件下保存6个月;0.5 mL制品置于(5±3)℃进行持续稳定性考察,分别测定顶空氧含量与水分,对两者进行Pearson相关系数分析并计算其回归方程。结果 ① 0.1 mL制品加速条件下,0~6个月顶空氧含量水分呈持续上升趋势,水分结果均<3.0%。两者Pearson相关系数为0.804,呈现强正相关。以顶空氧含量为x,水分含量为y,线性回归方程为y=0.450 1x+0.634 2,R^(2)为0.647 2;② 0.5 mL制品持续稳定性考察数据显示,顶空氧含量与水分Pearson相关系数为0.871,呈现强正相关。以氧含量为x,水分为y,线性回归方程为y=0.473 5x+0.657 6,R^(2)为0.758 8。结论 注射用A型肉毒毒素顶空氧含量与水分呈现强的正相关,可以建立两者之间的线性方程,并根据顶空氧含量预测不同条件稳定性试验中水分含量与趋势。

Objective To investigate the relationship between headspace oxygen content and water content of Botulinum toxin type A for injection in two sizes(0.1 mL and 0.5 mL). Methods 0.1 mL of the product was stored under accelerated conditions of(25±2) ℃ and 60%±5% relative humidity for 6 months, while the 0.5 mL product was store at(5±3) ℃ for ongoing stability study. and the headspace oxygen content and water content were measured separately, then Pearson correlation analysis was performed between the two contents and the regression equation was obtained. Results① Under the accelerated condition of 0.1mL product, the headspace oxygen content and water content showed a continuous upward trend from 0 to 6 months however the water content results were less than 3.0%. The Pearson correlation coefficient between the two contents was 0.804, showing a strong positive correlation. Taking oxygen content as x and water content as y, the regression equation was y=0.450 1x+0.634 2, and R^(2) was 0.647 2;②The data of ongoing stability study of 0.5 mL product showed that the Pearson correlation coefficient between headspace oxygen content and water content was 0.871, showing a strong positive correlation. Taking oxygen content as x and water content as y, the regression equation was y=0.473 5x+0.657 6, and R^(2) was 0.758 8. Conclusion The headspace oxygen content of Botulinum toxin type A for injection showed a strong positive correlation with water content, and a linear equation between them could be established, and the water content and trend in stability tests under different conditions could be predicted according to the headspace oxygen content.