Differential Scanning Calorimetry (DSC) in Solid-State Characterization of Solid Dispersions: A Practical Guide.

Differential Scanning Calorimetry (DSC) is one of the most widely employed and rapid thermal analysis techniques for early-stage solid-state characterization, particularly in the development of solid dispersions. As an indirect method, DSC detects transitions in solid-state properties through heat flow measurements, providing valuable insights into crystallinity, polymorphism, and miscibility. However, the accuracy and interpretation of DSC thermograms are highly sensitive to various experimental parameters, including heating and cooling rates, sample preparation, moisture content, and the thermal history of the material. These variables can introduce artifacts or mask thermal events, leading to misinterpretation of solid-state transitions. This review critically examines key thermodynamic and kinetic factors reported in literature that influence DSC measurements in the context of solid dispersions. Emphasis is placed on the mechanisms by which these variables affect endothermic and exothermic transitions and how such influences can be mitigated through experimental design. Practical recommendations are provided to improve method reliability, including optimal scan rates, sample handling techniques, and the use of complementary analytical tools such as X-ray powder diffraction (XRPD) and Fourier-transform infrared spectroscopy (FTIR) to support DSC findings. The primary objective of this review is to serve as a technical guide for researchers and formulation scientists aiming to generate reproducible and interpretable DSC data for solid dispersion systems. By understanding the limitations and best practices associated with DSC, researchers can enhance the reliability of solid-state characterization and make informed decisions in formulation development.