Thermogravimetric analysis (TGA) measures changes in mass of a sample as it is heated, allowing detection and measurement of chemical and physical processes like dehydration. TGA is useful for studying drug substance interactions with atmosphere, pyrolysis, decomposition, thermal stability, and dehydration. It is commonly used to regulate loss on drying in pharmaceutical monographs. Primary applications in pharmaceuticals include measuring free/bound water or solvent, thermal stability, and decomposition temperature. TGA provides a simple, inexpensive way to characterize pharmaceutical samples.

1. Thermogravimetric Analysis in Pharmaceuticals
The terms thermogravimetric analysis (TGA) describe any experimental method whereby
changes in mass are used to detect and to 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 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

2. or reactive gas may be used to purge and control the environment. The analysis is performed
by gradually raising the temperature and plotting the substances weight against temperature.
A computer is utilized to control the instrument and to process the output curves (temperature
verses weight).
Diagram of Thermobalance
Following is the TGA curve of the thermal decomposition of calcium oxalate monohydrate
with respect to temperature.
Diagram shows that calcium oxalate monohydrate decomposes in 3 distinct steps.
First step loss of water this relates to elimination and vaporisation of water of crystallisation.
Second step decomposition and formation of calcium carbonate and Third step further
decomposition to calcium oxide
Importance of TGA in Pharmaceuticals:
Usage of the TGA technique is extensive but arguably narrow, most studies using 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.

3. There is considerable interest in optimizing the removal of residual organic solvents from
dosage forms such as polylactide microspheres. There is 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.
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.), Compostional Analysis by Thermogravimetry, ASTM STP
97,American Society for Testing and Materials (1988).
 P.J. Haines (ed.) Principles of Thermal Analysis & Calorimetry