Quantitation of amorphicity by microcalorimetry
The amorphous state of solids is characterized by a higher chemical and physical reactivity and a hygroscopic behaviour. Furthermore processing of amorphous powders is often difficult, because of the instability. Fast crystallizations, precipitations and milling favour the formation of the amorphous state. Galenical processes like granulation, drying, lyophilization, mixing, may also induce amorphous regions in the drug products.
X-ray diffraction techniques can be used for the determination of the amorphicity of drug raw materials or drug products. Unfortunately, 10% is the detection limit, which in normal cases can be attained. Amorphous substances undergo an exothermic crystallization at temperatures above the glass transition point. Water which is a plasticizer decreases the temperature of the glass transition point, allowing the crystallization to occur at lower temperatures. The crystallization energy is measure of by microcalorimetry.
Examples show the influence of the choice of the experimental conditions, especially the influence of the amorphicity on the kinetic of the reaction. Critical steps are discussed for three different drug substances. Limits of detection in the magnitude of 1 % are possible using microcalorimetry.
Keywordsmicrocalorimetry quantitation of amorphicity
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