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 solution of crystalline sucrose, amorphous sucrose, clathrate warfarin sodium and amorphous warfarin sodium were 1474.08 +/- 37.78 cal/mol, - 3550.47 +/- 51.04 cal/mol, - 1.701 +/- 0.041 cal/g and - 7.386 +/- 0.226 cal/g, respectively. The observed linear relationship between the heat 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 complex system, such as the clathrate warfarin sodium (a complex of warfarin sodium, isopropyl alcohol and water). The solid state conversion process could also be monitored by measuring the energy changes associated with changes in crystallinity. (C) 1997 Elsevier Science B.V.