□ To better understand the properties of citric acid when used in solid dosage forms as an acid–base buffer, we initiated a study of its properties in the amorphous state. Such a state often arises during processes such as lyophilization and wet granulation. In view of inconsistencies in the literature concerning the glass transition temperature, Tg, of citric acid in the dry and hydrated states, we measured the Tg of samples formed by a melt-quench cool sequence in a DSC. We also used DSC to measure Tg', the glass transition temperature of the maximally freeze-concentrated solution. It was shown that dry citric acid has a Tg of 11°C, while that containing 8.6% water (equimolar) has a value of –25°C. The Tg' of a frozen solution of citric acid is –53°C. Measuring Tg for the dry and hydrated samples at various scanning rates allowed measurement of the activation energy for enthalpy relaxation at Tg and enabled estimation of the degree of fragility (or the strength parameter) for both samples. It was shown that citric acid is a fairly fragile liquid expected to exhibit non-Arrhenius dynamic behavior and that the presence of residual water at a level of 8.6% causes a decrease in fragility.
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