Beattie J Renwick, Barrett Lindsay J, Malone John F, McGarvey John J, Nieuwenhuyzen M, Kett Vicky L
Centre for Clinical Raman Microscopy, The Queen's University of Belfast, Belfast, United Kingdom.
Eur J Pharm Biopharm. 2007 Sep;67(2):569-78. doi: 10.1016/j.ejpb.2007.03.015. Epub 2007 Mar 28.
The aim was twofold; to demonstrate the ability of temperature-controlled Raman microscopy (TRM) to locate mannitol within a frozen system and determine its form; to investigate the annealing behavior of mannitol solutions at -30 degrees C. The different polymorphic forms of anhydrous mannitol as well as the hemihydrate and amorphous form were prepared and characterized using crystal or powder X-ray diffractometry (XRD) as appropriate and Raman microscopy. Mannitol solutions (3% w/v) were cooled before annealing at -30 degrees C. TRM was used to map the frozen systems during annealing and was able to differentiate between the different forms of mannitol and revealed the location of both beta and delta polymorphic forms within the structure of the frozen material for the first time. TRM also confirmed that the crystalline mannitol is preferentially deposited at the edge of the frozen drop, forming a rim that thickens upon annealing. While there is no preference for one form initially, the study has revealed that the mannitol preferentially transforms to the beta form with time. TRM has enabled observation of spatially resolved behavior of mannitol during the annealing process for the first time. The technique has clear potential for studying other crystallization processes, with particular advantage for frozen systems.
证明温控拉曼显微镜（TRM）在冷冻系统中定位甘露醇并确定其形态的能力；研究甘露醇溶液在-30℃下的退火行为。制备了无水甘露醇的不同多晶型形式以及半水合物和无定形形式，并根据需要使用晶体或粉末X射线衍射（XRD）以及拉曼显微镜进行表征。将甘露醇溶液（3% w/v）冷却后在-30℃下退火。在退火过程中使用TRM对冷冻系统进行成像，它能够区分不同形式的甘露醇，并首次揭示了冷冻材料结构中β和δ多晶型形式的位置。TRM还证实，结晶甘露醇优先沉积在冷冻液滴的边缘，形成一个边缘，在退火时会变厚。虽然最初对一种形式没有偏好，但该研究表明，随着时间的推移，甘露醇优先转变为β形式。TRM首次实现了在退火过程中观察甘露醇的空间分辨行为。该技术在研究其他结晶过程方面具有明显的潜力，对冷冻系统具有特别的优势。
