Investigation of Solid-State Hydrate-Anhydrous Phase Transformations of Dabigatran Etexilate Hemi-Edisylate
Jin Feng,
Changjin Lim,
Sihyun Nam,
Woojin Yoon,
Hoseop Yun,
Woo-Sik Kim,
Ji-Hun An
Affiliations
Jin Feng
Medical College, Anhui University of Science and Technology, Huainan 232001, China
Changjin Lim
School of Pharmacy, Jeonbuk National University, Jeonju 54896, Jeonbuk-do, Republic of Korea
Sihyun Nam
R&D Center, UniCel Lab, Uiwang 16079, Gyeonggi-do, Republic of Korea
Woojin Yoon
Department of Chemistry and Energy Systems Research, Ajou University, Suwon 16499, Gyeonggi-do, Republic of Korea
Hoseop Yun
Department of Chemistry and Energy Systems Research, Ajou University, Suwon 16499, Gyeonggi-do, Republic of Korea
Woo-Sik Kim
Functional Crystallization Center, Integrated Engineering Program, Department of Chemical Engineering, Kyung Hee University, Yongin 17104, Gyeonggi-do, Republic of Korea
Ji-Hun An
R&D Center, UniCel Lab, Uiwang 16079, Gyeonggi-do, Republic of Korea
In this study, a dabigatran etexilate edisylate (DBE) was prepared by the reaction crystallization of dabigatran etexilate (DBG) and edisilic acid. According to single crystal X-ray diffraction (SXRD), it was revealed that two DGB were combined with one edisylate and associated with one water for DBE monohydrate. Additionally, the hot stage microscopy showed that the DBE monohydrate was transformed to DBE amorphous solid and then finally shifted to the DBE anhydrate in solid-state. Using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and a hygroscopic test, it was confirmed that the phase transformation of DBE monohydrate to DBE anhydrate was irreversible. Additionally, any other crystal form of DBE anhydrate was not available because it was the most stable phase.
