Establishment of a cocrystal characterization method for sacubitril valsartan sodium
10.16438/j.0513-4870.2020-1811
- VernacularTitle:沙库巴曲缬沙坦钠共晶表征方法的建立研究
- Author:
Jing XIONG
1
;
De-zhong XU
2
;
Xin-yi XU
3
;
Yang LÜ
4
;
Shi-ying YANG
4
;
Si-cen WANG
5
Author Information
1. National Institutes for Food and Drug Control, NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, Beijing 102629, China; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
2. National Institutes for Food and Drug Control, NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, Beijing 102629, China
3. Chinese Pharmacopoeia Commission, Beijing 100061, China
4. Beijing Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
5. School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
- Publication Type:Research Article
- Keywords:
heart failure;
sacubitril valsartan sodium;
cocrystal;
characterization;
powder X-ray diffraction;
solid-state nuclear magnetic resonance spectroscopy;
ynamic vapor sorption;
hygroscopicity
- From:
Acta Pharmaceutica Sinica
2021;56(2):577-584
- CountryChina
- Language:Chinese
-
Abstract:
Sacubitril valsartan sodium (LCZ696) is an ionic cocrystal drug. The purpose of this study was to explore the cocrystal features of LC696 by establishing a variety of characterization methods, and thus provide basic research data for effective quality control. The cocrystal characteristics of LCZ696 and its tablets were identified by applying analytical means including powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), Raman spectra (RM), differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). The crystalline water and hygroscopicity of LCZ696 were analyzed by thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), hygroscopicity test and Karl Fischer reaction method. The results show that PXRD, FTIR, DSC and ssNMR can effectively distinguish the features of LCZ696 cocrystal, sacubitril monomer, valsartan monomer, and sacubitril-valsartan (1∶1) mixture. RM can be used as a supplementary approach. Combined with the analysis by TGA, DVS, hygroscopicity test and Karl Fischer reaction method results, LCZ696 contains 2.5 crystalline water molecules and is very hygroscopic; we recommend that LCZ696 be stored in an environment with a relative humidity below 60%. By characterizing the crystal features we can establish quality control measure and evaluate the stability of the drug tablets. This study provides data in support for the establishment of the LCZ696 quality standard.
