CHARACTERIZATION OF FROZEN AQUEOUS-SOLUTIONS BY LOW-TEMPERATURE X-RAY-POWDER DIFFRACTOMETRY

Purpose, A low temperature X-ray powder diffractometric (XRD) techniqu e has been developed which permits in situ characterization of the sol id-state of solutes in frozen aqueous solutions. Methods. A variable t emperature stage, with a working temperature range of -190 to 300 degr ees C, was attached to a wide-angle XRD. The stage was calibrated with a sodium chloride-water binary system. Results, When aqueous nafcilli n sodium solution (22% w/w) was frozen, eutectic crystallization of th e solute was not observed. However, annealing at -4 degrees C, caused crystallization of the solute. With increasing annealing time, there w as a progressive increase in the crystallinity of the solute. Studies were carried out with sodium nafcillin solutions ranging in concentrat ion from 20 to 50% w/w. The solid-state of the phase crystallizing fro m solution was independent of the solute concentration. Next, solution s of mono-and disodium hydrogen phosphate were individually frozen. On ly the latter crystallized as the dodecahydrate (Na2HPO4 . I2H(2)O). H owever when an aqueous buffer mixture of mono-and disodium hydrogen ph osphate was frozen. the former inhibited the crystallization of the la tter. Conclusions. Since freezing of solutions is the first step in ly ophilization, the XRD technique can provide a mechanistic understandin g of the alterations in solid-state that occur during freeze-drying. D SC has so far been the technique of choice to study frozen systems. Th e advantage of XRD is that it not only permits unambiguous identificat ion of the crystalline solid phase(s), but it also provides informatio n about the degree of crystallinity. While overlapping thermal events are difficult to interpret in DSC, XRD does not suffer from such a lim itation.