X-ray Diffractometry-Raman Spectroscopy

Cavatur and Suryanarayanan [1.164] have developed a low-temperature X-ray powder diffractometer (XRD) technique to study the solid states of solutes in frozen aqueous solutions. In frozen naftillin sodium solution (22% w/w), no eutectic crystallization was observed. Annealing at -4°C caused solute crystallization, which increased with annealing time. Two other products studied showed that XRD provides information about the degree of crystallinity without the interference of other events. 

Raman spectroscopy was used by Sane et al. [1.165] to quantitate structural changes in proteins freeze- or spray-dried. Monoclonal antibodies(e.g. RhuMAbVEGF) underwent secondary structural changes in the absence of a lyoprotectant. Increasing molar ratios of cryoprotectant could lead to complete structural preservation. The long-term stability of the dried proteins correlates with structural changes observed by Raman spectroscopy. 

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