Amorphousness and the glassy state

DSC and DTA allow the determination of glass transitions, the glass transition temperature and at temperatures above the of any crystallisation 

For materials in which a large proportion of glassiness is formed, DSC can lead to an estimate of the crystalline or amorphous (by subtraction) content provided the heat of fusion of the fully crystalline material is known. The heat of fusion of a sample can be percentified as a function of the heat of fusion of a standard giving the crystalline content. Clearly, the same polymorphic form should be present in both sample and standard. The technique has errors and can not be used to estimate the amorphous content when this is low, perhaps less than 5%. Re-scanning a glassy material may determine if it is subject to polymorphic modifications. 

In some cases, where a drug substance is highly insoluble, associated amorphous material may be reasonably morphologically stable. In these cases it may be advantageous to include some associated amorphous material to enhance the bioavailability of the product. For both hydrophobic and hydrophilic materials, the amorphous component associated with a crystalline substance can have a profound effect on the overall performance of the product. Extreme care should be taken to understand and quantify the amorphous material. Reduction of amorphous material in poorly soluble/hydrophobic materials may drastically reduce bioavailability. An increase in amorphous content in a hydrophilic material may cause reduction in chemical stability and transformation to an inappropriate form. 

In addition to conventional techniques used to observe amorphous material, such as DVS and XPRD, isothermal microcalorimetry and solution calorimetry can be used to observe and accurately quantify amorphous materials. 

Isothermal microcalorimetry. The study of amorphous materials using microcalorimetry relies on the physical properties of the amorphous fraction being significantly different to the crystalline form. In general, amorphous materials tend to be hydrophilic and thermodynamically unstable. If maintained in a high RH environment, the amorphous material would eventually 

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