抗体偶联药物抗CD30-MCC-DM1的制剂处方研究

Formulation study of anti-CD30-MCC-DM1

目的筛选并确定新型抗体偶联药物抗CD30-MCC-DM1(F0002-ADC)的制剂处方,解决该药溶解度偏低、冻干制剂含水量较高等问题,进而得到适用于该药物的制剂处方。方法对缓冲盐、pH值、蛋白保护剂以及助溶剂等条件或参数设计实验进行考察。结果得到了蛋白浓度5 g/L、pH 5.0、缓冲盐枸橼酸浓度10 mmol/L、蛋白保护剂蔗糖浓度6%(w/v)、表面活性剂聚山梨酯20浓度0.02%(w/v)以及助溶剂盐酸精氨酸浓度3%(w/v)的制剂处方,制得的冻干制剂含水量低于3%。结论该制剂配方能提高药物溶解度、降低冻干制剂含水量,并通过长期稳定性实验验证了该配方能满足F0002-ADC的临床需求。

Objective We aim to optimize and determine the formulation of anti-CD30-MCC-DM1(F0002-ADC)to improve its stability and reduce the moisture of its freeze-drying sample.Methods Experiments were designed to investigate the parameters such as buffer salts,pH,protein protectants,and solubilizers to find the optimal formulation of F0002-ADC.Results After screening,the best formulation was found to contain 5 g/L F0002-ADC,6%(w/v)sucrose,3%(w/v)Arg-HCl,0.02%(w/v)polysorbate-20 and 10 mmol/L citric acid,pH 5.0.Conclusions The formulation can improve the solubility of F0002-ADC,and reduce the moisture of its freeze-drying sample.Long-term stability experiments confirm the formulation meet the clinical requirements of F0002-ADC.