Zhengzheng Zhou1, Hok Man Chan1, Herman H-Y Sung2, Henry H Y Tong3, Ying Zheng4. 1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, SAR, China. 2. Department of Chemistry, The Hong Kong University of Science & Technology, Hong Kong, SAR,, China. 3. School of Health Sciences, Macao Polytechnic Institute, Macao, SAR, China. henrytong@ipm.edu.mo. 4. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, SAR, China. yzheng@umac.mo.
Abstract
PURPOSE: The purpose of this work was to develop thermal methods to identify cocrystal systems with stoichiometric diversity. METHODS: Differential scanning calorimetry (DSC) and hot stage microscopy (HSM) have been applied to study the stoichiometric diversity phenomenon on cocrystal systems of the model compound salicylic acid (SA) with different coformers (CCFs). The DSC method was particularly useful in the identification of cocrystal re-crystallization, especially to improve the temperature resolution using a slower heating rate. HSM was implemented as a complementary protocol to confirm the DSC results. The crystal structures were elucidated by single-crystal X-ray diffraction (SXRD). RESULTS: Two new cocrystal systems consisting of salicylic acid-benzamide (SA-BZD, 1:1, 1:2) and salicylic acid-isonicotinamide (SA-ISN, 1:1, 2:1) have been identified in the present work. The chemical structures of the newly discovered cocrystals SA-BZD (1:2) and SA-ISN (2:1) have been elucidated using X-ray single crystal and powder diffraction methods. CONCLUSIONS: The developed thermal methods could rapidly identify cocrystal systems with stoichiometric diversity, with the potential to discover new pharmaceutical cocrystals in the future.
PURPOSE: The purpose of this work was to develop thermal methods to identify cocrystal systems with stoichiometric diversity. METHODS: Differential scanning calorimetry (DSC) and hot stage microscopy (HSM) have been applied to study the stoichiometric diversity phenomenon on cocrystal systems of the model compound salicylic acid (SA) with different coformers (CCFs). The DSC method was particularly useful in the identification of cocrystal re-crystallization, especially to improve the temperature resolution using a slower heating rate. HSM was implemented as a complementary protocol to confirm the DSC results. The crystal structures were elucidated by single-crystal X-ray diffraction (SXRD). RESULTS: Two new cocrystal systems consisting of salicylic acid-benzamide (SA-BZD, 1:1, 1:2) and salicylic acid-isonicotinamide (SA-ISN, 1:1, 2:1) have been identified in the present work. The chemical structures of the newly discovered cocrystals SA-BZD (1:2) and SA-ISN (2:1) have been elucidated using X-ray single crystal and powder diffraction methods. CONCLUSIONS: The developed thermal methods could rapidly identify cocrystal systems with stoichiometric diversity, with the potential to discover new pharmaceutical cocrystals in the future.
Authors: Henry H Y Tong; Boris Y Shekunov; John P Chan; Cedric K F Mok; Henry C M Hung; Albert H L Chow Journal: Int J Pharm Date: 2005-05-13 Impact factor: 5.875