Iudicello Antonella, Genovese Filippo, Strusi Valentina, Dominici Massimo, Ruozi Barbara
Pharmaceutical Department, Azienda USL of Modena, Largo del Pozzo 71, 41121 Modena, Italy.
Nuclear Medicine Unit, Oncology and Hematology Department, Azienda Ospedaliero-Universitaria of Modena, Largo del Pozzo 71, 41124 Modena, Italy.
Pharmaceuticals (Basel). 2021 Sep 21;14(9):943. doi: 10.3390/ph14090943.
Stability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which could, in many cases, be longer. In practice, the pharmacy-based centralized preparation may require preparation in advance for administration, for example, on weekends, holidays, or in general when pharmacies may be closed. We report an innovative strategy for storing resuspended solutions of azacitidine, a well-known chemotherapic agent, for which the manufacturer lists maximum stability of 22 h. By placing the syringe with the azacitidine reconstituted suspension between two refrigerant gel packs and storing it at 4 °C, we found that the concentration of azacitidine remained above 98% of the initial concentration for 48 h, and no change in color nor the physicochemical properties of the suspension were observed throughout the study period. The physicochemical and microbiological properties were evaluated by HPLC-UV and UHPLC-HRMS analysis, FTIR spectroscopy, pH determination, visual and subvisual examination, and sterility assay. The HPLC-UV method used for evaluating the chemical stability of azacitidine was validated according to ICH. Precise control of storage temperature was obtained by a digital data logger. Our study indicates that by changing the storage procedure of azacitidine reconstituted suspension, the usage window of the drug can be significantly extended to a time frame that better copes with its use in the clinical environment.
制药行业进行的稳定性研究主要是为了满足许可要求。因此，由于细菌学原因，稀释后或复溶后的稳定性数据通常仅限制为24小时，而不考虑在许多情况下可能更长的真正物理化学稳定性。在实际操作中，基于药房的集中配制可能需要提前准备以供给药，例如在周末、节假日或一般药房可能关闭的时候。我们报告了一种创新策略，用于储存阿扎胞苷（一种知名化疗药物）的复溶溶液，该药物制造商列出的最大稳定性为22小时。通过将装有阿扎胞苷复溶悬浮液的注射器置于两个制冷剂凝胶包之间并在4°C下储存，我们发现阿扎胞苷的浓度在48小时内保持在初始浓度的98%以上，并且在整个研究期间未观察到颜色变化或悬浮液的物理化学性质改变。通过高效液相色谱-紫外检测（HPLC-UV）、超高效液相色谱-高分辨质谱分析（UHPLC-HRMS）、傅里叶变换红外光谱（FTIR）、pH测定、目视和亚目视检查以及无菌检测对物理化学和微生物学性质进行了评估。用于评估阿扎胞苷化学稳定性的HPLC-UV方法根据国际人用药品注册技术协调会（ICH）进行了验证。通过数字数据记录器精确控制储存温度。我们的研究表明，通过改变阿扎胞苷复溶悬浮液的储存程序，该药物的使用窗口可以显著延长至更能适应其在临床环境中使用的时间段。
