Theoretical Model and Experimental Investigations on Solution-Mediated Polymorphic Transformation of Theophylline: From Polymorph I to Polymorph II
Manli Zhu,
Yongli Wang,
Fei Li,
Ying Bao,
Xin Huang,
Huanhuan Shi,
Hongxun Hao
Affiliations
Manli Zhu
National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Yongli Wang
National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Fei Li
National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Ying Bao
National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Xin Huang
National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Huanhuan Shi
National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Hongxun Hao
National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
In this work, theophylline was selected as the model compound to study and simulate the solution-mediated polymorphic transformation. The polymorph I and polymorph II of theophylline were prepared and fully characterized. Raman and UV spectra methods were carried out to observe the phase transformation of theophylline from polymorph I to polymorph II at different temperatures. The theoretical models, including dissolution model, nucleation model, and growth model, were established to describe and simulate the transformation processes. By combination of experiments and simulations, the controlling steps of the transformation processes were discussed. The effects of temperature and/or solvent on the transformation processes were evaluated. This work can shed light on the polymorphic transformation processes.
