Pyne A, Suryanarayanan R
College of Pharmacy, University of Minnesota, 55455, USA.
Pharm Res. 2001 Oct;18(10):1448-54. doi: 10.1023/a:1012209007411.
To study the solid-state and phase transitions of glycine, (i) in frozen aqueous solutions, and (ii) during freeze-drying.
X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC) were used to analyze the frozen systems. In situ freeze-drying in the sample chamber of the diffractometer enabled characterization of phase transitions during freeze-drying.
Transitions in frozen systems. Rapid (20 degrees C/min) or slow (2 degrees C/min) cooling of aqueous solutions of glycine (15% w/w) to -70 degrees C resulted in crystallization of beta-glycine. Annealing at -10 degrees C led to an increase in the amount of the crystalline phase. When quench-cooled by immersing in liquid nitrogen, glycine formed an amorphous freeze-concentrate. On heating, crystallization of an unidentified phase of glycine occurred at approximately -65 degrees C which disappeared at approximately -55 degrees C, and the peaks of beta-glycine appeared. Annealing caused a transition of beta- to the -gamma- form. The extent of this conversion was a function of the annealing temperature. Slower cooling rates and annealing in frozen solutions increased the crystalline beta-glycine content in the Iyophile. Freeze-drying of quench-cooled solutions led to the formation of gamma-glycine during primary drying resulting in a lyophile consisting of a mixture of beta- and -gamma-glycine. The primary drying temperature as well as the initial solute concentration significantly influenced the solidstate of freeze-dried glycine only in quench-cooled systems.
The cooling rate, annealing conditions and the primary drying temperature influenced the solid-state composition of freeze-dried glycine.
研究甘氨酸在（i）冷冻水溶液中以及（ii）冷冻干燥过程中的固态及相变情况。
采用X射线粉末衍射法（XRD）和差示扫描量热法（DSC）分析冷冻体系。在衍射仪样品室中进行原位冷冻干燥，以表征冷冻干燥过程中的相变。
冷冻体系中的转变。将甘氨酸（15% w/w）水溶液快速（20℃/分钟）或缓慢（2℃/分钟）冷却至-70℃会导致β-甘氨酸结晶。在-10℃退火会使结晶相的量增加。当通过浸入液氮进行骤冷时，甘氨酸形成无定形冷冻浓缩物。加热时，甘氨酸的一种未知相在约-65℃结晶，在约-55℃消失，随后β-甘氨酸的峰出现。退火导致β-型向γ-型转变。这种转变的程度是退火温度的函数。较慢的冷却速率以及在冷冻溶液中退火会增加冻干物中结晶β-甘氨酸的含量。对骤冷溶液进行冷冻干燥会在一次干燥过程中形成γ-甘氨酸，从而得到一种由β-甘氨酸和γ-甘氨酸混合物组成的冻干物。仅在骤冷体系中，一次干燥温度以及初始溶质浓度会显著影响冷冻干燥甘氨酸的固态。
冷却速率、退火条件和一次干燥温度会影响冷冻干燥甘氨酸的固态组成。
