Thermodynamic and kinetic mechanism of phase transformation of levofloxacin hydrochloride |
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| Institution: | 1. National Engineering Research Center for Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;2. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;3. School of Chemical Engineering and Technology, Hainan University, Haikou 570208, China;1. European Powder and Process Technology, Longfellow Drive, Kettering, United Kingdom;2. KU Leuven, Department of Chemical Engineering, Process and Environmental Technology Lab, J. De Nayerlaan 5, 2860 Sint-Katelijne-Waver, Belgium;3. Beijing University of Chemical Technology, Beijing Advanced Centre of Smart Matter Science and Engineering, Beijing, China;1. National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;2. State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;3. School of Chemical Engineering and Technology, Hainan University, Haikou 570208, China;1. State Key Laboratory of Ocean Engineering, Shanghai Jiao Tong University, Shanghai 200240, China;2. Institute of Marine Equipment, Shanghai Jiao Tong University, Shanghai 200240, China;3. CHEC Dredging Co., Ltd., Shanghai 200136, China;4. National Engineering Research Center of Dredging, Shanghai 200120, China;1. Institute of Manufacturing Engineering, Huaqiao University, Xiamen 361021, China;2. National & Local Joint Engineering Research Center for Intelligent Manufacturing Technology of Brittle Material Products, Huaqiao University, Xiamen 361021, China;3. School of Mechanical Engineering, Xiangtan University, Xiangtan 411105, China;1. Civil and Environmental Engineering Faculty, Amirkabir University of Technology, Tehran, Iran;2. Civil Engineering Faculty, Science and Research Branch, Islamic Azad University, Tehran, Iran;1. National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;2. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;3. School of Chemical Engineering and Technology, Hainan University, Haikou 570228, China |
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| Abstract: | In this work, thermodynamic and kinetic factors that affect formation and phase transformation process of different solid forms of levofloxacin hydrochloride were investigated in detail. Dynamic vapor sorption experiments (DVS) and varying temperature-powder X-ray diffraction (VT-PXRD) experiments were carried out to study moisture-dependent stability, thermal stability as well as the transformation process between Form I and Form II. Critical water activities of levofloxacin hydrochloride were determined in temperature range of 5.0–45.0 °C. Raman spectroscopy was applied to in situ monitor the temperature-induced phase transformation and the hydration process of levofloxacin hydrochloride, and one possible mechanism consisting of multiple chemical equilibria was proposed to analyze the effect of thermodynamic and kinetic factors on the formation and transformation of different solid forms. Results show that the anhydrate, Form II would transform to the monohydrate, Form I more easily with the increasing water content. And the transition point moves toward higher water contents as the temperature increases. The results suggested that, except for thermodynamic factors, kinetic factors also play an essential role in controlling the solid forms of polymorphic compounds. |
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| Keywords: | Levofloxacin hydrochloride Crystallization Phase transformation Hydrate |
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