Coupling between thermoanalytical and spectroscopical instruments enlarges the research and development possibilities within the chemical and especially also within the pharma-ceutical organic industry considerably.

The thermobalance itself enables to generate valuable quantitative and precise data about mass changes of the sample in respect to temperature and/or time.

The coupling between a thermobalance and a FTIR instrument for a spectroscopical analysis of the evolved gases enables a straight-forward qualitative and quantitative analysis. Impurities with a low molecular weight, which were introduced during the production pathway of the substance under investigation, namely chemical precursors and chemical side products, also solvents and water may be easily detected. These impurities may have physically or chemically quite different relations to the main component. First of all the relation may follow one of the great number of possible phase diagrams. The two main diagrams are the eutectic system and the solid solutions with and without miscibility gaps. The relation of the impurities is for these two cases completely different. The main component and the impurities are in the eutectic system a physical mixture of crystals of the pure components. Whereas the impurities in solid solutions are more or less homogeneous dissolved within the crystals of the main component. Another relation is the normal situation with organic substances, namely that a surface adsorption is practically always present of specific impurities. The nature and the quantity of adsorbed substances, preferably also water and solvents is depending on the specific surface area, the surface roughness and the hydrophilic – lipophilic surface characteristic. Still further varieties are based on the formation of additional chemical entities starting with the main component and substances such as water and solvents, hydrochloric and also hydrobromic acid which can lead to hydrates, solvates, salts and even by another possibility within the phase diagrams namely molecular compounds in different stoichiometric ratios. Also non-stoichiometric systems are existing, which are making a characterization rather tedious, because it could be caused by the crystal structure of the main component, also by an instability problem and furthermore by the molecular structure of the partners. Another possibility is an interaction of impurities preferably also water and solvents leading to inclusion compounds.

The capability, the versatility, the sensitivity and the molecular specificity of the TG –FTIR brought this instrumentation to an extremely valuable method in the characterization of organic and especially also pharmaceutical substances. Examples are discussed, which had been carefully investigated in a cooperative study and the results obtained are compared with literature data. The substances of our research goals are carbamazepine, caffeine and theophylline and some of their solid state varieties [ 1,2] .

References:

[ 1] M. E. Auer, S. Cianferani, U. J. Griesser, U. Ch. Hofmeier, and M. Szelagiewicz, Bâle Meeting, XXIXe Journéés de Calorimétrie et d`Analyse Thermique-AFCAT, 23^rd Annual Meeting of the Swiss Society for Thermal Analysis and Calorimetry-STK (1998) Basel, Switzerland

"TG-FTIR: A Powerful Tool for the Investigation of Pseudopolymorphs"

[ 2] U. J. Griesser, M. Szelagiewicz, , U. Ch. Hofmeier, S. R. Byrn, and A. Burger, PhandTA 4, 4^th Symposium and Workshops on Pharmacy and Thermal Analysis, (1999) University of Karlsruhe, Germany

"Old and New Aspects of the Polymorphism of Caffeine and Theophylline and its Implications in Drug Formulation"

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