Thermodynamic and kinetic mechanism of phase transformation of levofloxacin hydrochloride--颗粒学报PARTICUOLOGY

Liu, H., Zhang, X., Wang, T., Huang, X., Chen, K., Wang, N., . . . Hao, H. (2022). Thermodynamic and kinetic mechanism of phase transformation of levofloxacin hydrochloride. Particuology, 66, 59-70. https://doi.org/10.1016/j.partic.2021.08.009

Thermodynamic and kinetic mechanism of phase transformation of levofloxacin hydrochloride

Han Liu a, Xiunan Zhang a, Ting Wang a b, Xin Huang a b *, Kui Chen ^a, Na Wang ^a, Shanshan Yu ^a, Yuyuan Dong ^a, Hongxun Hao ^{a b c *}

a National Engineering Research Center for Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
b Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
c School of Chemical Engineering and Technology, Hainan University, Haikou 570208, China

10.1016/j.partic.2021.08.009

Volume 66, July 2022, Pages 59-70

Received 2 August 2021, Revised 23 August 2021, Accepted 24 August 2021, Available online 15 September 2021, Version of Record 5 November 2021.

E-mail: x_huang@tju.edu.cn; hongxunhao@tju.edu.cn

Highlights

• Phase transformation process of levofloxacin hydrochloride in two states.

• Thermodynamic and kinetic factors affecting phase transformation process.

• One mechanism for analyzing the formation and transformation process.

• Effective methods to control different solid forms.

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.

Graphical abstract

Keywords

Levofloxacin hydrochloride; Crystallization; Phase transformation; Hydrate

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