Department of Pharmaceutical and Food Technology, Complutense University of Madrid, 28040, Madrid, Spain.
Department of Basic Health Sciences, Area of Pharmacy and Pharmaceutical Technology, Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain.
Sci Rep. 2024 Apr 18;14(1):8975. doi: 10.1038/s41598-024-58473-1.
For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.
对于大多数细胞毒性药物制剂，如硼替佐米，单位剂量信息不可用。此外，对于打开后的药物制剂的物理化学稳定性缺乏信息；这些信息对于患者在连续就诊时的给药至关重要，并且可能会影响每个患者的成本。我们建议的物理化学稳定性研究旨在确定冷藏和临床实践条件下复溶液体产品的保质期。该评估扩展到了用打开的小瓶内容物预填充的小瓶和即用型注射器。稳定性测试设计包括规定的储存条件和复溶注射用硼替佐米的关键物理化学参数。此外，该方法包括杂质的测定、使用光电二极管阵列监测平均峰的纯度、质量平衡的控制、使用激光衍射分析仪监测亚可见颗粒、以及稳定性规格的设定。对于化学稳定性研究，使用稳定性指示 HPLC 方法测定硼替佐米及其降解产物的量。在整个稳定性研究过程中对样品进行了物理检查，并监测了它们的 pH 值。硼替佐米（2.5mg/mL）在 0.9%氯化钠中在 5±3°C（冷藏）下储存在聚丙烯注射器和小瓶中时，稳定 7 天，避光。此外，在模拟临床使用的储存条件（20-30°C 和避光）下，其稳定性可维持 24 小时。该方案提供了小瓶中复溶后和预填充冷藏注射器中的稳定性；该方案可用于减少浪费并节省成本。
