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  • Thermogravimetric Analysis in Pharmaceuticals

    The terms Thermogravimetric Analysis (TGA) describes an experimental method whereby changes in mass are used to detect and measure the chemical and, less frequently, the physical (e.g., sublimation) processes that occur on heating a reactant under investigation.

    Data obtained by this method are often more accurate than those from other techniques.

    TGA instruments can be applied to the study of:

    • Interaction of the atmosphere with the drug substance
    • Pyrolysis
    • Compound decomposition
    • Thermal stability
    • Dehydration (or desolvation) processes
    • Thermogravimetry is also a popular method for regulating loss on drying in numerous monographs.

    Primary Applications in Pharmaceuticals:

    • Free water or solvent
    • Bound water or solvent (hydrate or solvate)
    • Thermal Stability
    • Decomposition temperature

    The Thermogravimetric Analysis (TGA) instrument usually consists of a high-precision balance and sample pan. The pan holds the sample material and is located in a furnace or oven that is heated or cooled during the experiment. A thermocouple is used to accurately control and measure the temperature within the oven. The mass of the sample is constantly monitored during the analysis. An inert or reactive gas may be used to purge and control the environment. The analysis is performed by gradually raising the temperature and plotting the weight of the substance against temperature. A computer is utilized to control the instrument and to process the output curves (temperature versus weight).

    Diagram of Thermobalance

    Following is the TGA curve of the thermal decomposition of calcium oxalate monohydrate with respect to temperature.

    The diagram shows that calcium oxalate monohydrate decomposes in 3 distinct steps. First step loss of water relates to the elimination and vaporization of water of crystallization. The second step is decomposition and formation of calcium carbonate and the Third step is further decomposition to calcium oxide.

    Importance of TGA in Pharmaceuticals:

    Usage of the TGA technique is extensive but arguably narrow, most studies use the method to measure the temperature range in which dehydration occurs and the quantity of water lost from solid drug or excipient systems. TGA to obtain a more detailed analysis of the kinetics of dehydration and the nature of the drug or excipient–water interaction, particularly when used in conjunction with complementary techniques such as XRD and DSC

    There is considerable interest in optimizing the removal of residual organic solvents from dosage forms such as polylactide microspheres. There is an important potential role for TGA in this respect, as appropriate kinetic analysis of the loss process may allow the design of manufacturing protocols whereby the solvent is removed more effectively. Finally, the issue of volatility or sublimation of components in dosage forms is widely recognized but poorly understood, with problems including the loss of the drug itself, preservatives, or plasticizers. This is again an area whereby a more sophisticated understanding of the kinetics of loss, obtained through relatively simple TGA experiments, could prove to be of great value to the formulator.

    Overall, TGA remains a simple, inexpensive, and conceptually accessible means of characterizing pharmaceutical samples.

    FAQs:

    What is Thermogravimetric analysis used for?

    Thermogravimetric analysis (TGA) is an analytical technique method of thermal analysis that is used to determine and measure the mass of the sample over time as the temperature changes.

    What is the advantage of Thermogravimetric analysis?

    The advantage of Thermogravimetric analysis is the characterization of materials through the analysis of characteristic decomposition patterns. This technique is useful for the study of polymeric materials like plastic fibers, thermoplastic, coating paints, fuels, food, and pharmaceuticals.  
     

    References:

    • Thermal Analysis of Pharmaceuticals, edited by Duncan Q.M. Craig, Mike Reading
    • Principles and Applications of Thermal Analysis, edited by Paul Gabbott
    • Vogel’s Textbook of quantitative chemical analysis, sixth edition, page no.507-511
    • G. R. Heal, Thermogravimetry & Derivative Thermogravimetry”
    • C. M. Earnest (Ed.), Compositional Analysis by Thermogravimetry, ASTM STP 97, American Society for Testing and Materials (1988).
    • P.J. Haines (ed.) Principles of Thermal Analysis & Calorimetry