- Optimization and process improvement for LCZ696 by employing quality by design (QbD) principles
-
Efforts toward optimization and improvement for the synthesis of LCZ696 employing design of experiment (DoE) principles are described. By increasing the purity of intermediates and mitigating impurity risk during each step, a telescoped process was developed via removal of isolation of intermediates with the overall yield increased by 28.5% from 45.3% to 73.8%. And the whole production cycle was also shortened from 12 days to 7 days with simplified operations and restored process greenness. Meanwhile, the corresponding impurity profile was thus studied in detail and well documented.
- Chen, Zhijun,Wang, Hailong,Wu, Shuming,Wang, Jian,Zhang, Chenxia,Yang, Hua,Wang, Zhongqing
-
supporting information
(2020/09/10)
-
- AMORPHOUS POWDER COMPRISING AN ANGIOTENSIN RECEPTOR BLOCKER AND A NEUTRAL ENDOPEPTIDASE INHIBITOR
-
Several methods for the preparation of an amorphous powder comprising a 1:1 stoichiometric mixture of the trisodium salts of Valsartan and Sacubitril are described, as well as the resulting amorphous powder, pharmaceutical compositions containing it, and their use in the treatment of essential hypertension and/or cardiac failure.
- -
-
Page/Page column 15
(2017/02/09)
-
- SOLID STATE FORMS OF TRISODIUM SALT OF VALSARTAN/SACUBITRIL COMPLEX AND SACUBITRIL
-
The present invention describes an amorphous form of trisodium salt of valsartan sacubitril complex and a process for the preparation of same comprising: reacting sacubitril sodium and valsartan disodium or sacubitril and valsartan in the presence of a sodium ion source in one or more solvents to obtain a solution; and obtaining the trisodium salt of valsartan sacubitril complex by the removal of the solvent from the solution or by adding an anti-solvent to the solution. The crystalline form of sacubitril sodium is characterized by x-ray powder diffraction pattern having characteristic peaks expressed in terms of 2-theta at about 6.3°, 12.0°, 13.8°, 16.5°, 18.3°, 20.0° and 23.8°±0.2° (2θ).
- -
-
Page/Page column 30
(2017/02/09)
-
- Method for preparing LCZ696
-
The invention discloses a method for preparing LCZ696. Please see the synthesis route in the specification. When sodium acetate is used as alkali in the compound III preparation process, the conversion rate is high, hydrolysis impurities are few, system stability is good, and the reaction time is greatly shortened; in the compound I preparation process, acetone and normal heptanes with the mass ratio between 5 to 1and 10 to 1 serve as cocrystallization solvent, the reaction temperature of 35-45 DEG C is adopted, a sodium hydroxide solution is dropwise added into a reaction system at a certain speed at the temperature of 35-45 DEG C, generation of hydrolysis products can be greatly reduced, the solid precipitation state is good, purity is high, aminolysis impurities and hydrolysis impurities can be effectively controlled, and the LCZ696 can directly serve as crude drug to be used for preparations.
- -
-
Paragraph 0047; 0048; 0049
(2016/10/09)
-
