Effect of Cryogrinding on Chemical Stability was observed (degree of crystallinity 31%), but this effect is not as significant as in the case of milling carried out at liquid nitrogen temperature. This finding agrees with results reported for other systems like those of indometh- acin or trehalose. For the former, amorphous state was reached only after 60 min of cryogrinding (13), while during mechanical treatment at room temperature more than 1200 min (9) are required to get a similar effect. Similarly, complete amorphization of trehalose in the traditional ball mill was reached even after 1380 min of grinding (10). It should also be noted that Villiers and Tiedt (28) have found that prolonged milling of furosemide in a traditional ball mill resulted in a practical limit in particle size reduction within a relatively short time (30 min). Indeed, even after 1440 min of milling in the conventional device the degree of crystallinity was estimated to be greater than 25%. Our results indicate that in the high-impact cryogenic device we are able to effectively reduce the particle size to a level probably hardly attainable during room temperature treatment. As already mentioned in the Introduction, solid-state amorphization of pharmaceuticals is a very problematic issue, and several concepts were proposed. Some of them suggest that the process of amorphization occurring during mechanical treatment in a mill cannot be regarded as glass transition in the traditional sense (15). However, the presence of the glass transition event can be detected by monitoring the change of thermodynamic variables such as heat capacity. In Fig. 2 we present a DSC thermogram recorded upon heating (10°C/min) of a sample cryomilled for 180 min. Within the examined temperature range, two thermal events were observed: the glass transition at 55°C (calculated as a midpoint of the glass transition step) 3225 followed by recrystallization at 74°C. Thus, characteristic for the glass transition, jump in the heat capacity really occurred. This means that the drug can certainly reach the glassy state upon cryogrinding. The exothermic peak around Tc= 74°C was ascribed to recrystallization of the cryomilled sample. Such a thermal behavior is often observed in the case of ground samples. Next, time-dependent XRD measurements at room temperature and 10% RH were carried out to test physical stability of the amorphous furosemide prepared by cryomil- ling. In Fig. 3 we present diffraction patterns recorded at specified time intervals. As the storage time increases, initially amorphous furosemide tends towards a more stable crystalline form. This is visible as an increase in Bragg’s peaks intensities. However, between 3 and 21 days of storage, the degree of crystallinity does not significantly increase and maintains at an almost constant value of 6%. The slowing down of the crystallization progress is quite often observed with cryomilled samples. For example, when the degree of crystallinity of the initially amorphous cryomilled ziprasidone base and ziprasidone hydrochloride reached 30% and 37%, respectively (that happened after 2 weeks of storage at room temperature), no significant changes in the crystallization progress were observed later on (29). We claim that the degree of crystallinity remains constant at 6% because of our specific storage conditions. Crystallization of cryomilled furosemide was monitored after placing it into the Lindemann glass capillary of 2 mm Fig. 2 DSC thermogram recorded upon heating (10°C/min) of furosemide cryomilled for 180 min. Fig. 3 Changes in the X-ray diffraction patterns of furosemide cryomilled for 60 min and stored at 25°C and 10% RH.