Abstract
Purpose. To test the hypothesis that the choice of counterion in salt formation would generally result in a change in the glass transition temperature, Tg, in relation to the nature of the interaction between the ionized parent structure and its counterion.
Methods. Various alkali metal salts of indomethacin (IMC), lithium (Li+), sodium (Na+), potassium (K+), rubidium (Rb+), and cesium (Cs+) IMC were prepared as amorphous solid powders by lyophilization. The Tg was measured using differential scanning calorimetry or modulated-temperature differential scanning calorimetry. The spectroscopic properties of these salts were analyzed using Fourier transform-Raman and Fourier transform-infrared spectroscopy.
Results. A comparison of the Tg values of the five salts showed Tg values in the order of Li+ > Na+ > K+ > Rb+ > Cs+, which is consistent with an order of decreasing ionic radius, and hence an increased charge density and an increased electrostatic interaction energy between the carboxylate ion and the alkali metal cation. Spectroscopic data support this interpretation by showing that the different salts exhibit spectral differences only in the region of the carboxylate group.
Conclusions. Changes in Tg due to salt formation for alkali metal salts of IMC mainly result from differences in ionic interaction between the oppositely charged ions that appear to be related to the size/charge ratio of the counterion.
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Tong, P., Taylor, L.S. & Zografi, G. Influence of Alkali Metal Counterions on the Glass Transition Temperature of Amorphous Indomethacin Salts. Pharm Res 19, 649–654 (2002). https://doi.org/10.1023/A:1015310213887
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DOI: https://doi.org/10.1023/A:1015310213887