5.1.2. Phase Behaviour

For crystal cell units, it is important to confirm that the API exists, and in the case of NCC, co-former exist as a co-crystal by non-ionic interaction using appropriate analytical techniques [162]. Furthermore, the extent of polymorphism must be considered when determining the stability of a system and attempting to predict API release from that system.

The most frequently used techniques for investigating the phase behavior of NCM include the use of DSC, TGA, PXRD, and ScXRD. By investigating the thermal behavior and crystallinity of such systems, valuable complementary information can be generated for the characterization and quality control of NCM formulations and technologies [163].

Modulated temperature DSC (MTDSC) is sensitive and has a high separation capacity with overlapping thermal events as quasi-static material properties, and frequency dependency of thermal events are monitored, whereas TGA measures sample mass during the heating process and is convenient for determining the presence of solvates and hydrates [163].
