Her L M, Deras M, Nail S L
Department of Industrial Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
Pharm Res. 1995 May;12(5):768-72. doi: 10.1023/a:1016280113800.
Addition of electrolytes to solutions of non-crystallizing solutes can cause a significant decrease in the glass transition temperature (Tg') of the maximally freeze-concentrated solution. For example, addition of 2% sodium chloride to 10% solutions of dextran, PVP, lactose, and sucrose causes a decrease in Tg' of 14 degrees to 18 degrees C. Sodium phosphate has a smaller effect on Tg' and is unusual in that 1% to 2% sodium phosphate in 10% PVP causes a second glass transition to be observed in the low-temperature thermogram, indicating a phase separation in the freeze concentrate. Comparison of DSC thermograms of fast-frozen solutions of sucrose with and without added sodium chloride shows that electrolyte-induced reduction of Tg' is not caused by a direct plasticizing effect of the electrolyte on the freeze concentrate. Measurement of unfrozen water content as a function of temperature by a pulsed nmr method shows that the most likely mechanism for electrolyte-induced changes in Tg' is by increasing the quantity of unfrozen water in the freeze concentrate, where the unfrozen water acts as a plasticizer and decreases Tg'. The correlation time (tau c) of water in the freeze concentrate is in the range of 10(-7) to 10(-8) seconds. The results underscore the importance of minimizing the amount of added salts to formulations intended for freeze drying.
向非结晶溶质溶液中添加电解质会导致最大冷冻浓缩溶液的玻璃化转变温度（Tg'）显著降低。例如，向10%的右旋糖酐、聚乙烯吡咯烷酮、乳糖和蔗糖溶液中添加2%的氯化钠会使Tg'降低14摄氏度至18摄氏度。磷酸钠对Tg'的影响较小，其不同寻常之处在于，在10%的聚乙烯吡咯烷酮中添加1%至2%的磷酸钠会在低温热重图中观察到第二个玻璃化转变，这表明冷冻浓缩物中发生了相分离。对添加和未添加氯化钠的快速冷冻蔗糖溶液的差示扫描量热法（DSC）热重图进行比较表明，电解质引起的Tg'降低不是由电解质对冷冻浓缩物的直接增塑作用导致的。通过脉冲核磁共振方法测量未冻水含量随温度的变化表明，电解质引起Tg'变化的最可能机制是增加冷冻浓缩物中未冻水的量，其中未冻水起到增塑剂的作用并降低Tg'。冷冻浓缩物中水的相关时间（τc）在10^(-7)至10^(-8)秒范围内。这些结果强调了将添加到冻干制剂中的盐量降至最低的重要性。
