PDF(Pubmed)
Abstract：
During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking agents essential for the treatment of patients in intensive care units. The present study describes the pharmaceutical development of an injectable 2 mg/mL solution of pancuronium bromide (PC) in a very short lapse of time. The sterile solution was compounded into a good manufacturing practice grade A clean room, filtered (0.2 µm) and filled into 10 mL type I glass, manually sealed with bromobutyl rubber stoppers. A novel HPLC-MS stability indicating method for pancuronium quantification and its degradation product was developed and validated. This fast, sensitive and straightforward method was used to study the stability of the formulation using a semi-predictive method, enabling a very fast attribution of a temporary shelf-life, which was confirmed by a classic prospective stability study. The production line and the analytical tools set-up were performed in six weeks and the semi-predictive stability study was conducted in 90 days, allowing us to predict a shelf life, which was successfully confirmed by prospective study. In conclusion, using innovative methods, we were able to rapidly overcome the shortage of a critical drug.
摘要：
在COVID-19大流行的最初几个月，国际医疗产品供应链紧张，导致对重症监护病房患者治疗至关重要的神经肌肉阻断剂的可用性中断。本研究描述了在非常短的时间内可注射的2mg/mL溴化库溴铵（PC）溶液的药物开发。将无菌溶液混合到良好的生产实践A级洁净室中，过滤（0.2µm）并填充到10mLI型玻璃中，用溴丁基橡胶塞手动密封。开发并验证了一种新型的HPLC-MS稳定性指示方法，用于板库溴铵及其降解产物的定量。这么快,使用半预测方法，使用灵敏而直接的方法来研究制剂的稳定性，能够非常快速地确定临时保质期，这得到了经典的前瞻性稳定性研究的证实。生产线和分析工具设置在六周内进行，半预测稳定性研究在90天内进行，让我们能够预测保质期，这已被前瞻性研究成功证实。总之,使用创新的方法，我们能够迅速克服关键药物的短缺。
