Thermal analytical techniques are invaluable methods for characterizing the properties and structure of pharmaceutical materials. These techniques analyze the change in a specific property of the analyte as a function of temperature. This kind of analysis provides valuable insights into the thermodynamics and kinetics involved and thus the properties of the analyte.
The main thermal analysis techniques used in the pharmaceutical sector are differential scanning calorimetry (DSC), differential thermal analysis (DTA), thermogravimetric analysis (TGA), and dynamic mechanical analysis (DMA).
Different techniques study different properties of the material - DSC studies enthalpy, DTA tracks the difference in temperature of the analyte against a reference, TGA measures the mass of the material, and DMA analyses the deformation.
Differential scanning calorimetry
DSC is the most commonly used thermal analysis technique in pharmaceutical sciences. It is used to determine the difference in rate of heat flow into the sample and a reference material. DSC instruments are available in a range of sensitivities for robust screening and quality control applications.
Initially, two types of DSC instruments were available - heat-flux DSC (hf-DSC) and power compensation DSC (pc-DSC). However, recent advances in DSC have given rise to two more versions - Tzero DSC™ and modulated DSC (M-DSC®) - with significant improvement in sensitivity and resolution.
- M-DSC® - An M-DSC® differs from traditional DSC in the temperature profile applied to the sample and the separation of the resulting heat flow signal. Traditional DSC gives a single signal for all the thermal events occurring within the experimental temperature range, making it tough to interpret the data. M-DSC® measures both the heat capacity and the kinetic components from the difference, thus making it easy to interpret the results.
- Tzero DSC™ - Tzero DSC™ technology offers significant improvements in sensitivity and temperature resolution of the transitions due to its cell design which gives two differential measurements and enables the calibration of heat capacitance and thermal resistance of the sensors as a function of temperature.
The advanced DSC technologies allow accurate characterization of a wide range of amorphous and crystalline pharmaceutical materials including tablets, proteins, and frozen solutions.
TGA exploits change in mass to identify and measure the physical and chemical processes that take place on application of heat to the sample. This technique is useful in analyzing any kinetic processes that involve loss of mass.
It is used in pharmaceutical sciences for the characterization of hydrates and the determination of vaporization, decomposition, or sublimation temperatures. Instruments that allow TGA and DSC analysis at the same time for a single sample are commercially available and offer accurate results while saving time.
Thermal analysis techniques are used in solid-state characterization in a range of applications in pharmaceutical research. These include:
- Study of physicochemical properties of crystalline solids
- Identification of polymorphic forms of a substance
- Study of solid-state kinetics such as accelerated stability, decomposition, and the effects of aging on different pharmaceutical formulations
- Developing optimal formulations and cycles for lyophilization
- Analyzing the effects of lyophilization
Polymorphs have very different physicochemical properties and identification of the formation of polymorphs is very crucial during product development. DSC has been successfully used to identify polymorphic transitions due to its ability to analyze samples under a wide range of temperatures that are needed for polymorph formation. DSC can also be used in the monitoring of polymorph development during different storage or manufacturing conditions including heating, grinding, and drying.
DSC has been used to characterize a solid dispersion system of polyvinylpyrrolidone and felodipine. DSC revealed partial miscibility between the components which led to significant improvement in the felodipine’s dissolution and release kinetics. DSC has also been combined with other techniques to analyze the dissolution of solid dispersions of PEG 15000 and ketoprofen.
M-DSC has been widely used in the optimization of lyophilization and the study of amorphous engineered particles of itraconazole with cellulose acetate phthalate and polyvinyl acetate phthalate. Several published studies show the use of M-DSC to characterize a wide range of solid dispersions and polymer-based formulations such as drug-loaded hydrogels, film-coated pellets, and solid dispersions of itraconazole.