Title :

X-ray Diffraction and Theoretical Calculation–Supported Formation of Polymorphic Cocrystals Discovered Through Thermal Methods: A Case Study

Author(s) :

Zhou, Zhengzheng [Auteur]
Southern Medical University [Guangzhou]
Calatayud, Monica [Auteur]
Laboratoire de chimie théorique [LCT]
Contreras-García, Julia [Auteur]
Laboratoire de chimie théorique [LCT]
Li, Liang [Auteur]
Sun Yat-sen University [Guangzhou] [SYSU]
Tong, Henry [Auteur]
Macao Polytechnic Institute [Macao]
Zheng, Ying [Auteur]
University of Macau [UMac]

Journal title :

Journal of Pharmaceutical Sciences

Publisher :

Wiley

Publication date :

2019

ISSN :

0022-3549

English keyword(s) :

salicylic acid
cocrystal
polymorphism
density functional theory (DFT)
thermal methods
modulated temperature DSC (MTDSC)

HAL domain(s) :

Chimie/Chimie théorique et/ou physique
Chimie/Cristallographie
Sciences du Vivant [q-bio]/Sciences pharmaceutiques

English abstract : [en]

Polymorphism commonly exists in the preparation of cocrystals and has attracted widespread attention from both the pharmaceutical industry and academia. However, few studies have examined how to discover polymorphic ...
Show more >Polymorphism commonly exists in the preparation of cocrystals and has attracted widespread attention from both the pharmaceutical industry and academia. However, few studies have examined how to discover polymorphic cocrystals and their potential formation mechanism. In this study, we report the novel discovery of salicylic acid: 3-nitrobenzamide (SA-3NBZ) polymorphic cocrystals by thermal methods. The formation mechanism is elucidated based on theoretical calculations. SA-3NBZ polymorphic cocrystals with molar ratio of 1:1 and 2:2 were discovered using the combination of differential scanning calorimetry and hot stage microscopy. Single-crystal X-ray diffraction analysis confirmed this discovery. Density functional theory calculations corrected with dispersion were conducted to illustrate the energetic stabilization of SA polymorphic cocrystals. Compared with the starting materials, formation of the cocrystals at 1:1 and 2:2 present a weak stabilization with overall energy reduction of −0.01 and −0.05 eV/molecule, respectively. The calculated noncovalent interactions index further suggests that intralayer hydrogen bonds and van der Waals forces contribute to these weak interactions. The density functional theory calculations are in good agreement with the X-ray diffraction data. Hence, thermal analysis is a simple and reliable method to discover polymorphic cocrystals.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189

Source :

Harvested from HAL