Thermal methods of analysis

The development of thermal analysis methods in materials research has led to a plethora of new methodologies since the elaboration of the first thermal method by by Le Chatelier and Robert-Austen [16,86], Thermal analysis consists of a group of techniques in which a physical property of a material is measured as a function of temperature at the same time when the substance is subjected to a controlled increase, or in some cases, decrease of temperature. Temperature-programmed techniques, such as DTA [87-89], TGA [87], DSC [53,90], TPR [91,92], and TPD [93-96], contribute to perform a more complete characterization of materials. 

The Physical Chemistry of Materials Energy and Environmental Applications 

Thermal analysis methods are defined as those techniques for which one or more properties of a sample are determined as a function of an externally 

Thermogravimetry is a measure of the thermally induced weight loss of a material as a function of the applied temperature.44- 6 TG analysis is restricted to transitions that involve either a gain or loss of mass and is most commonly used to study desolvation processes and compound decomposition. TG analysis is a very useful method for the quantitative determination of the total volatile content of a solid and can be used as an adjunct to Karl Fischer titrations for the determination of moisture. As such, it readily permits the distinction between solvates and the anhydrous forms of a given compound. When performed in conjunction with an auxiliary technique (such as gas chromatography or infrared spectroscopy), one may also obtain compound-specific decomposition information. 

When a solid is capable of decomposing by means of several discrete, sequential reactions, the magnitude of each step can be separately evaluated. The TG analysis of compound decomposition can also be used to compare the stability of similar compounds. In general, the higher the decomposition temperature of a given compound, the greater would be its stability. 

Other than its ability to demonstrate the anhydrous nature of genuine polymorphic materials, one extremely useful aspect of TG analysis is in the differentiation and characterization of solvatomorphs. The methodology is particularly useful in the determination of a solvate phase in the presence of its anhydrate phase, or vice versa. 

The most commonly encountered form of lactose is its a-anomer, which is obtained in the form of a monohydrate phase. The anhydrous form of the a-anomer is known to be very hygroscopic and difficult to either obtain or handle. The /Tanomer of lactose is obtained as an anhydrate phase, which apparently has no tendency to form any hydrate phases. The thermal properties of these materials have been discussed.47 The theoretical water content for the a-monohydrate phase is 5.0% w/w, so in principle one can use thermogravimetry to determine either the anhydrate phase content in a largely monohydrate sample or the monohydrate phase content in a largely anhydrous sample. 

The first measurements of temperature as a function of time during a cooling or heating process were made by J. F. E. Rudberg in Sweden in 1829. Other early workers were M. L. Frankenheim (1837) and H. Le Chatelier (1883 and 1887), both of whom seem to have been unaware of the earlier work.271 Le Chatelier was followed by W. C. Roberts-Austin, who initiated differential thermal analysis in 1899. The development of this technique, from its introduction to the 1970s, has been discussed.272 Hungarian work in thermal analysis over the period 1950-1990 has been described.273 

From the discussion presented of reactions in solids, it should be apparent that it is not practical in most cases to determine the concentration of some species during a kinetic study. In fact, it may be necessary to perform the analysis in a continuous way as the sample reacts with no separation necessary or even possible. Experimental methods that allow measurement of the progress of the reaction, especially as the temperature is increased, are particularly valuable. Two such techniques are thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC). These techniques have become widely used to characterize solids, determine thermal stability, study phase changes, and so forth. Because they are so versatile in studies on solids, these techniques will be described briefly. 

Thermoanalytical methods comprise a series of techniques in which a property is determined at different temperatures or as the temperature changes continuously. The property measured may include the mass of the sample (TGA), the heat flow to the sample (DSC), the magnetic character of the sample (TMA), or some other property such as dimensional changes. Each of these types of measurements gives information on some change undergone by the sample, and if the change is followed over time, it is possible to derive kinetic information about the transformation. 

When heated, many solids evolve a gas. For example, most carbonates lose carbon dioxide when heated. Because there is a mass loss, it is possible to determine the extent of the reaction by following the mass of the sample. The technique of thermogravimetric analysis involves heating the sample in a pan surrounded by a furnace. The sample pan is suspended from a microbalance so its mass can be monitored continuously as the temperature is raised (usually as a linear function of time). A recorder provides a graph showing the mass as a function of temperature. From the mass loss, it is often possible to establish the stoichiometry of the reaction. Because the extent of the reaction can be followed, kinetic analysis of the data can be performed. Because mass is the property measured, TGA is useful for 

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Wendlandt, W. W. Thermal Methods of Analysis, 2nd ed. Wiley New York, 1986. 

Phase transitions, whether first-order or second-order, are potent sources of instability of solid drugs and can usually be detected and studied by thermal methods of analysis (e.g., DSC, TGA, TMA, ODSC, DMA, DEA). In crystalline solids, typical first-order transitions are polymorphic or desolvation transitions. In amorphous solids, second-order transitions, such as glass transitions, are common. 

Thermal methods of analysis were used to study the polymorphism associated with pindolol [29]. The overlapping melting endotherms of the different forms were separated by peak fitting analysis and grouping of materials by the temperature of... 

A very useful complement to ordinary powder x-ray diffraction is variable-temperature XRD. In this method, the sample is contained on a stage that can be heated to any desired temperature. The method is extremely useful in the study of thermally induced phenomena, and it is seen as a complement to thermal methods of analysis. 

Haines, P. J. Thermal Methods of Analysis Principles, Applications and Problems, Blackie A P, 1995. 

Thermal methods of analysis can be defined as those techniques in which a property of the substance under study is determined as a function of an externally applied and programmed temperature. Dollimore [1] has listed three conditions that define the usual practice of thermal analysis ... 

Thermal methods have found extensive use in the past as part of a program of preformulation studies, since carefully planned work can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [2], It should be noted, however, that the use of differential scanning calorimetry (DSC) for such work is less in vogue than it used to be. Nevertheless, in appropriately designed applications, thermal methods of analysis can be used to evaluate compound purity,... 

W.W. Wendlandt, Thermal Methods of Analysis, Wiley-Interscience, New York, 1964. 

Wendlandt, W. W. "Thermal Methods of Analysis" Interscience Publishers, New York, NY, 1964. 

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