Effect of Cryogrinding on Chemical Stability Fig. 8 (a) The 1HNMR spec- trum of the main degradation product formed upon cryomilling panel (b) enlarged region from 6.8 ppm to 8.6 ppm. 3231 It has been well established that micronized drugs, partially as well as completely amorphous, have an extensive surface area, and for this reason uncontrolled chemical reactions are likely to proceed more quickly as compared to their crystalline counterparts. The rapid growth of chemical reactivity in the amorphous region is often linked to an increasing level of molecular mobility or moisture content (7). It can thus be hypothesized that the increment of Imp.1 observed upon increasing milling time is related to enhanced chemical reactivity of the amorphous material rather than to any negative effect caused by high- impact milling process itself. To clarify that hypothesis, chemical stability of amorphous furosemide prepared by cryomilling in the solid state and in solution was investigated.