Dynamic vapor sorption as a tool for characterization and quantification of amorphous content in predominantly...

It is well established that pharmaceutical processing can cause disruption of the crystal structure, leading to generation of amorphous content in crystalline materials. The presence of even a small amount of amorphous form, especially on the surface of crystalline material, can affect processing, performance, and stability of a drug product. This necessitates the need to quantify, monitor, and control the amorphous form. Numerous analytical techniques have been reported for the quantification of amorphous phase, but issues of sensitivity, suitability, limit of detection, and quantitation pose significant challenges. The present review focuses on use of dynamic vapor sorption (DVS) for quantification of amorphous content in predominantly crystalline materials. The article discusses (1) theoretical and experimental considerations important for developing a quantification method, (2) methods used for quantification of amorphous content, (3) basis for selecting a suitable methodology depending on the properties of a material, and (4) role of various instrument and sample-related parameters in designing a protocol for quantification of amorphous content. Finally, DVS-based hyphenated techniques have been discussed as they can offer higher sensitivity for quantification of amorphous content.