USE OF SOLUTION CALORIMETRY TO DETERMINE THE EXTENT OF CRYSTALLINITY OF DRUGS AND EXCIPIENTS

A solution calorimetry method was developed to quantitatively examine mixtures of amorphous and crystalline sucrose or warfarin sodium based on the energy differences between their solid forms. The heats of sol ution of crystalline sucrose, amorphous sucrose, clathrate warfarin so dium and amorphous warfarin sodium were 1474.08 +/- 37.78 cal/mol, - 3 550.47 +/- 51.04 cal/mol, - 1.701 +/- 0.041 cal/g and - 7.386 +/- 0.22 6 cal/g, respectively. The observed linear relationship between the he at of solution and the percent of the crystalline form present in the sample provided a rapid and convenient way to quantitatively determine the crystallinity of a common drug excipient (sucrose) and/or a compl ex system, such as the clathrate warfarin sodium (a complex of warfari n sodium, isopropyl alcohol and water). The solid state conversion pro cess could also be monitored by measuring the energy changes associate d with changes in crystallinity. (C) 1997 Elsevier Science B.V.