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Quinine Acesulfamates

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journal contribution
posted on 23.11.2016 by Jianhui Li, Xue Fu, Jiaoyang Li, Minmin Kong, Huaguang Yu, Jianming Wang, Zongwu Deng, Hailu Zhang
Pharmaceutical salts have been traditionally used in drug formulation. As a salt former, acesulfame (AH), an aliphatic calorie-free sweetener, is actively being employed. Acesulfamates of active pharmaceutical ingredients (APIs) may provide a pleasant sweet taste along with modified physicochemical properties. In this paper, four quinine (QN) salts were obtained with AH, including two 1:1 anhydrous forms (QNAH11a and QNAH11b), one monohydrate of 1:1 salt (QNAH111), and one 1:2 anhydrous forms (QNAH12). The resulting salts were fully characterized by a range of analytical methods. Crystal structures of QNAH11a, QNAH111, and QNAH12 were determined by single-crystal X-ray diffraction, and the crystal structure of QNAH11b was solved from powder X-ray diffraction data by Rietveld refinement. Ionization states for all samples were confirmed by 13C solid-state NMR spectra. The mutual transformation and thermodynamic relationships of these solid forms were revealed via slurry conversion experiments and differential scanning calorimetry measurements. Additionally, enhanced solubility was observed for each acesulfamate when compared with the pure free base. This study should further highlight the potential of AH as a pharmaceutical salt/cocrystal former.