Quantitation of crystallinity in substantially amorphous pharmaceuticals and study of crystallization kinetics by X-ray powder diffractometry

The first object was to develop an X-ray diffractometric method for the detection and quantification of crystalline sucrose when it occurs as a mixture with amorphous sucrose. Standards consisting of amorphous sucrose physically mixed with 1 to 5 weight percent crystalline sucrose were prepared. The sum of the background subtracted integrated intensities of the 12.7°2θ (6.94 Å) and 13.1°2θ (6.73 Å) sucrose diffraction peaks were linearly related to the weight percent crystalline sucrose. The limits of detection and quantitation of crystalline sucrose were 0.9% and 1.8% w/w, respectively. The second object was to study the kinetics of crystallization of sucrose as a function of temperature (at 102, 105 and 110°C under a water vapor pressure of 0 Torr) and water vapor pressure (17.4, 19.8 and 21.4 Torr at 27°C). In all cases, the crystallization kinetics was best described by the Avrami-Erofe'ev model (three-dimensional nucleation).