Derksen M W, van de Oetelaar P J, Maris F A
Department of Quality Assurance, NV Organon, Akzo Nobel, Oss, The Netherlands.
J Pharm Biomed Anal. 1998 Jul;17(3):473-80. doi: 10.1016/s0731-7085(97)00216-1.
The purpose of this study is to improve the efficiency in the search for a suitable specification for the residual moisture content in a freeze-dried product. A near-infrared spectroscopic (NIRS) method was developed for the measurement of the residual moisture content. Samples with a wide range of residual moisture contents were stored for two months at 8, 50, and 60 degrees C. Because of the non-destructive character of the NIRS method initially the residual moisture content and, subsequently, the content of the active ingredient could be measured in the same sample vials after storage. Plots of the residual moisture content against the content of the active ingredient were made for storage at 50 and 60 degrees C. For this only 69 samples were needed in the stability study for the assay determination while traditionally a five-fold of samples is needed because of the high intra-batch variability of the residual moisture content. The plots at 50 and 60 degrees C were combined with the Arrhenius relationship between degradation rate constant and temperature. The maximal allowable residual moisture content was calculated with product shelf-lives of 2 and 3 years and storage temperatures of 20, 25, and 30 degrees C, respectively.
本研究的目的是提高寻找冻干产品中残留水分合适规格的效率。开发了一种近红外光谱（NIRS）方法用于测量残留水分含量。将具有广泛残留水分含量范围的样品在8、50和60摄氏度下储存两个月。由于NIRS方法具有非破坏性，最初可以在储存后的同一样品瓶中测量残留水分含量，随后测量活性成分的含量。绘制了在50和60摄氏度下储存时残留水分含量与活性成分含量的关系图。在稳定性研究中，对于含量测定仅需要69个样品，而传统上由于残留水分含量的批次内高变异性需要五倍数量的样品。将50和60摄氏度下的关系图与降解速率常数和温度之间的阿累尼乌斯关系相结合。分别根据产品2年和3年的保质期以及20、25和30摄氏度的储存温度计算了最大允许残留水分含量。
