Correspondence - Vial breakage during freeze-drying: crystallization of sodium chloride in sodium chloride-sucrose frozen aqueous solutions
Correspondence - Vial breakage during freeze-drying: crystallization of sodium chloride in sodium chloride-sucrose frozen aqueous solutions
复制标题
DOI：
10.1002/jps.20854
复制
发表时间：
2007-07-01
影响因子：
3.8
通讯作者：
Yu, L.
中科院分区：
文献类型：
--
作者：
Milton, N.;Gopalrathnam, G.;Yu, L.
本研究的目的是评估氯化钠-蔗糖冷冻溶液的氯化钠结晶和小瓶菌株。使用差示扫描量热法 (DSC) 和应变计仪器瓶对氯化钠-蔗糖溶液进行了研究。氯化钠浓度随固定浓度的蔗糖变化，以鉴定在加热过程中观察到结晶的组合物，并使用应变测量小瓶检查该组合物。 1:1 (w/w) 比例的氯化钠-蔗糖溶液的 DSC 加热热分析图显示在约 -45 ℃ 处有氯化钠结晶放热。在应变测量瓶中检查该组合物显示应变增加，这对应于放热的温度。小瓶破裂是含有甘露醇溶液的一种现象，这与冷冻溶液中甘露醇的结晶有关。这些数据还表明，小瓶应变和破损与溶质结晶和水结晶（从无定形相释放形成冰）和体积膨胀有关。结果表明，在开发冻干制剂时，了解赋形剂比例的影响（特别是在含有结晶和非结晶赋形剂的系统中）以及热历史的重要性。 (c) 2007 年 Wiley-Liss, Inc.
The purpose of this study was to evaluate sodium chloride-sucrose frozen solutions with regard to sodium chloride crystallization and vial strain. Sodium chloride-sucrose solutions were studied using Differential Scanning Calorimetry (DSC) and a strain gauge instrumented vial. The sodium chloride concentration was varied with a fixed concentration of sucrose to identify a composition where crystallization was observed during heating and this composition was examined using the strain-gauged vials. DSC heating thermograms of a 1:1 (w/w) ratio of sodium chloride-sucrose solution show a sodium chloride crystallization exotherm at approximately -45 degrees C. Examination of this composition in a strain-gauged vial shows an increase in strain, which corresponds to the temperature of the exotherm. Vial breakage is a phenomenon reported for mannitol containing solutions, which is associated with crystallization of mannitol in frozen solution. These data also suggest that vial strain and breakage is associated with the crystallization of solutes and the crystallization of water, which is released from the amorphous phase to form ice, and volume expansion. The results demonstrate the importance of understanding effect of excipient ratios, specifically in systems containing crystallizing and non-crystallizing excipients, and thermal history when developing freeze-dried formulations. (c) 2007 Wiley-Liss, Inc.