Role of water in the solid-state properties of crystalline and amorphous sugars.

摘要

In the processing of pharmaceutical solids, disruption of the crystalline structure often occurs, leading to varying degrees of disorder which range from a completely amorphous structure to low levels of surface defects. It is important to be able to detect and quantitate such disorder, since it represents a higher energy or metastable state, relative to the crystalline state. It is also desirable to understand, predict and possibly overcome any undesirable tendencies for reversion to the crystalline state. This thesis is concerned with the assessment of disorder produced in different crystalline solids as a result of processing and the important role that water and additives play in affecting the tendencies toward crystallization from the amorphous state.;The percent disorder in various samples of sucrose have been estimated by x-ray powder diffraction, density, heats of crystallization, and water vapor sorption, with emphasis on comparing the results obtained with the four techniques, as well as probing the lower limits of detection. Although there was good agreement, water vapor sorption, was shown to be the best technique by far, to accurately detect very low levels of disorder.;Through the use of these techniques, measurements of the percent disorder and the nature of the remaining crystal form(s) have been determined for three crystal hydrates, ;The crystallization behavior of sucrose from the amorphous state and the effect that various additives, lactose, trehalose and raffinose may exert on this solid state transformation has also been studied. The presence of these additives in colyophilized form retarded the crystallization of sucrose by influencing both nucleation and growth steps.