ASSESSMENT OF DISORDER IN CRYSTALLINE SOLIDS

In the processing of pharmaceutical solids, disruption or activation o f the crystalline structure often leads to varying degrees of disorder through the formation of defects and amorphous regions. Since percent disorder of processed samples must be assessed quantitatively using p remixed standard samples of highly crystalline and amorphous solids, i n the past, a number of questions about the validity of such an approa ch have been raised. Using sucrose as a model solid, a comprehensive a ssessment of such disorder has been carried out on predetermined mixtu res of crystalline and amorphous samples, as well as on crystalline sa mples mechanically milled for various periods of time. Particular emph asis was placed on determining low levels of disorder in highly crysta lline samples, since most techniques can detect no less than about 10% disorder. With predetermined mixtures, measurements of X-ray powder d iffraction, density and heats of crystallization revealed good lineari ty with the percent disorder and acceptable detectability down to abou t 10%, as expected. However, using water vapor sorption measurements u nder very carefully controlled conditions proved effective in being ab le to detect disorder as low as 1%. A comparison of these four methods for estimating the percent disorder of milled samples of sucrose gave very consistent results, once the underlying factors that make these techniques sensitive to the concentration of amorphous structure prese nt were recognized and taken into account.