4.2.2. Differential Scanning Calorimetry (DSC)

DSC is a thermal analytical technique that provides qualitative and quantitative information as a function of time and temperature in respect of thermal changes in materials that involve endothermic or exothermic processes, or changes in heat capacity [81].

DSC is used for the determination of melting point, glass transition temperature, and purity of samples. When applied to NCM products, it is useful in determining changes in crystallinity, glass transition of stabilizing material, and the presence of more than one polymorphic form of the API. This is especially important for API that occurs in different polymorphic forms. Moreover, some top-down techniques like HPH can lead to a batch with an amorphous fraction. This, in turn, could lead to a significant increase in saturation solubility. The DSC of a pure drug, a physical mixture of drug and excipients (stabilizer), and the final formulation, which may be in dried form, is routinely done as pre-formulation and post-formulation quality tests [82].

Kocbek et al. prepared Pluronic® 68 stabilized ibuprofen nanosuspensions. The study results indicated the formation of a eutectic mixture of the drug and Pluronic® 68. In this case, DSC revealed a lower temperature melting peak representing the melting of the eutectic system, and a second peak representing the melting of the excess ibuprofen. Based on the position of the second peak, it was estimated that ibuprofen was in excess after eutectic formation [83].

Similarly, DSC was used to investigate the changes in the crystallinity of itraconazole (ITR) after the nanoprecipitation and drying processes or possible interactions between the API and excipients [84]. The results obtained indicated a small change in melting temperature of ITR, which were attributable to the reduction in PS and were deemed to not have been a consequence of CPP. The results also showed the presence of an amorphous component of ITR and confirmed the presence of both crystalline and amorphous ITR [84].

Although DSC cannot be used to establish the chemical nature of a sample being tested, the results can be useful for determining whether samples exhibit different thermal properties and can therefore distinguish differences relating to material identity, specific solid-state forms, and/or purity [85].
