Differential Scanning Calorimetry

Differential Scanning Calorimetry (DSC) measures the heat released or absorbed by a sample as its temperature changes over time. The working principle involves comparing the heat flow required to raise the temperature of a sample against a reference material, typically an empty pan or inert substance.

1. Basic Components of DSC Equipment:

- Furnace: Houses the sample and reference material.
- Thermal Sensors: Measure the temperature of the sample and reference.
- Cooling System: Controls the furnace temperature.
- Gas Supply System: Provides inert gases like nitrogen or argon to prevent oxidation.
- Computer System: Collects and processes thermal data.

2. Operating Principles

The DSC process involves these key steps:

1. Sample Preparation: The test sample is placed in a small metal pan, while an identical empty or inert pan is used as the reference.
2. Heating Process: The furnace heats both pans following a predefined temperature program (e.g., linear temperature ramp).
3. Heat Flow Comparison: As the sample undergoes thermal events (e.g., melting, crystallization, decomposition), heat is absorbed or released. The sensors detect the heat flow difference between the sample and the reference.
4. Data Recording: The heat flow is plotted as a function of time or temperature, producing a DSC curve.

DSC Curve : The DSC curve represents the variation in heat flow as a function of temperature. Peaks on the curve correspond to thermal events occurring within the sample.

- Endothermic Peaks: Indicate heat absorption, such as melting.
- Exothermic Peaks: Indicate heat release, such as crystalliz.

A diagram of a temperature Description automatically generated

Fig 1. An example of a DSC curve: exothermic peak (heat release) and endothermic peak (heat absorption)

Information Derived from DSC Curves:

- Phase Transition Temperatures: Melting, crystallization, or decomposition points.
- Specific Heat Capacity: Heat required to raise the temperature of one unit mass by 1°C.
- Transition Enthalpy: Heat absorbed or released during a phase change.
- Sample Purity: Narrow, symmetric melting peaks suggest high purity.
- Thermal Stability: The thermal stability of a sample can be determined using DSC by identifying its decomposition temperature.

3. Pharmaceutical Applications of DSC

- Purity Assessment: Sharp, symmetrical melting peaks indicate high purity.
- Polymorphism Detection: Different polymorphic forms exhibit distinct melting points.
- Stability Studies: Changes in DSC curves over time indicate stability or degradation.
- Drug-Excipient Interactions: Variations in melting points and peak shapes help identify interactions.
- Glass Transition Temperature (Tg): Tracks transitions between amorphous and crystalline states.

4. Applications of DSC in Solid Dispersion Research

The DSC technique can analyze the solid-state properties of the initial active pharmaceutical ingredient (API) and solid dispersions after formulation. For instance, when investigating the phase characteristics of solid dispersions composed of PEG 6000 and itraconazole using DSC, the dispersions were prepared via solvent evaporation. DSC analysis of pure PEG 6000 revealed three endothermic peaks, corresponding to the melting transitions of its three distinct crystalline forms.

- The results indicate that itraconazole reduces the formation of polymer crystals with melting points at 56°C and 59°C but promotes the formation of crystals with a melting point at 63°C. All analyzed solid dispersions exhibit the presence of crystalline itraconazole, suggesting that the drug is not completely dispersed within the polymer matrix. However, the appearance of an endothermic peak around 85-90°C in the DSC curves of all dispersions indicates the presence of at least one additional crystalline phase of itraconazole: the glassy itraconazole phase.
- The protective effect of the polymer is evident at low drug concentrations, as no recrystallization exothermic peaks are detected. However, at drug concentrations of 80% or higher, an exothermic peak corresponding to recrystallization appears around 117°C. At room temperature, at least three distinct phases can be differentiated: the polymer phase, crystalline itraconazole, and glassy itraconazole. The findings of this study demonstrate the simultaneous existence of multiple drug phases within a solid dispersion system.