Two novel cocrystals of lamotrigine with isomeric bipyridines and in situ monitoring of the cocrystallization

Shichao Du; Yan Wang; Songgu Wu; Bo Yu; Peng Shi; Lin Bian; Dejiang Zhang; Jie Hou; Jingkang Wang; Junbo Gong

doi:10.1016/j.ejps.2017.06.001

Two novel cocrystals of lamotrigine with isomeric bipyridines and in situ monitoring of the cocrystallization

Eur J Pharm Sci. 2017 Dec 15:110:19-25. doi: 10.1016/j.ejps.2017.06.001. Epub 2017 Jun 3.

Authors

Shichao Du¹, Yan Wang¹, Songgu Wu¹, Bo Yu¹, Peng Shi¹, Lin Bian², Dejiang Zhang¹, Jie Hou¹, Jingkang Wang³, Junbo Gong⁴

Affiliations

¹ School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin, China.
² School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
³ School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin, China; Key Laboratory Modern Drug Delivery and High Efficiency in Tianjin University, Tianjin, China.
⁴ School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin, China; Key Laboratory Modern Drug Delivery and High Efficiency in Tianjin University, Tianjin, China. Electronic address: junbo_gong@tju.edu.cn.

PMID: 28587788
DOI: 10.1016/j.ejps.2017.06.001

Abstract

Crystal engineering strategy was applied to develop new solid forms of lamotrigine. Two novel cocrystals of lamotrigine forming with 4,4'-bipyridine (2:1) and 2,2'-bipyridine cocrystal (1:1.5) were successfully obtained by neat grinding and liquid assisted grinding. The novel cocrystals were fully characterized and confirmed by X-ray diffraction, thermal and spectroscopic analysis. DXRxi Raman microscope was also used to identify the cocrystals. The factors such as solvent and the structure of coformers which influenced the cocrystal formation were discussed. Furthermore, the novel cocrystals were both obtained by slurry crystallization. Process analytical technologies including focused beam reflectance measurement and attenuated total reflectance Fourier Transform Infrared were applied to investigate the cocrystallization process and the mechanism. HPLC analysis showed that the dissolution rate and the solubility of the two novel cocrystals were both improved.

Keywords: 2,2′-Bipyridine (PubChem CID: 1474); 4,4′-Bipyridine (PubChem CID: 11107); Cocrystal screening; Cocrystallization process; Dissolution; Isomeric bipyridines; Lamotrigine; Lamotrigine (PubChem CID: 3878).

MeSH terms

2,2'-Dipyridyl / chemistry*
Crystallization
Humans
Isomerism
Lamotrigine
Molecular Conformation
Pyridines / chemistry*
Solubility
Triazines / chemistry*

Substances

Pyridines
Triazines
2,2'-Dipyridyl
Lamotrigine
4,4'-bipyridyl