scholarly journals Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging

Crystals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 922
Author(s):  
Xiao Juan Liu ◽  
Yang Zhang ◽  
Xue Zhong Wang

In situ ATR-FTIR spectroscopy and imaging and image analysis were applied to the study of the multicomponent co-crystallization process involving S-valsartan and sacubitril in which LCZ696 crystals were formed. LCZ696 is a combination drug for use in heart failure that was approved by the FDA in 2015 following development by Novartis Pharmaceuticals. Though much work was reported on LCZ696 about its pharmacokinetic and pharmacodynamic effects in the evaluation and clinical testing, less attention was paid to study on the co-crystallization process. LCZ696 crystals have shown difficulties in filtration mainly due to the small particle size. In this work, LCZ696 crystals were prepared successfully by S-valsartan and sacubitril, and characterized by SEM, XRPD, TG-DSC and ATR-FTIR. ATR-FTIR and imaging and image analysis were used to monitoring solution concentration and investigating the co-crystallization mechanism. It revealed that the nucleation process was very slow compared with the transformation process, which is indication that the co-crystallization was controlled by nucleation. LCZ696 crystals are composed of very thin hexagonal plates, which seems indicating that LCZ696 crystals grow mainly in two size dimensions. Stirrer speed and crystal seeds were found to have noticeable effect on the induction time, transformation time and crystal size distribution. The Johnson-Mehl-Avrami equation was found to be able to describe the co-crystallization process.

Author(s):  
Manuel Henry ◽  
François E Puel ◽  
Philippe D Perrichon ◽  
Caroline Wisniewski ◽  
Gilles Fevotte

The batch cooling crystallization of an industrial active pharmaceutical ingredient that exhibits a needle-like habit was investigated. A model of the time variations of key physical properties of particles (crystal size distribution CSD and specific area) was designed using an approach based on the simple population balance equation. The experiments were monitored thanks to three in-situ process analytical sensors (Mid-IR spectroscopy, in-situ microscopy and laser backscattering). Primary and secondary surface nucleation mechanisms as well as growth of the main crystal dimension (length) were described resulting in a six parameter model. The model roughly represents the effects of different cooling strategies on the supersaturation profile, the CSD and the specific area of the final particles. First, a very weak primary nucleation occurs leading to an initial population of a few large crystals. A second population of crystals is generated afterwards through secondary nucleation mechanisms. The particles issued from the second burst of nucleation largely dominate (in mass and in number) the final overall population. Second, two important features of the crystallization process are outlined, which are commonly observed during the industrial crystallization of APIs (Active Pharm. Ing.) in impure mother liquors.


2020 ◽  
pp. 49-52
Author(s):  
Trine Aabo Andersen

A new fast measuring method for process optimization of sucrose crystallization using image analysis based on high quality images and algorithms is introduced. With the mobile, non-invasive at-line system all steps of the sucrose crystallization can be measured to determine the crystal size distribution. The image analysis system is easy to operate and is as well an efficient laboratory solution with user-friendly and customized software. In comparison to sieve analysis, image analyses performed with the ParticleTech Solution have been proven to be reliable.


2020 ◽  
Vol 27 (1) ◽  
pp. 204-215
Author(s):  
Hongkai Zhao ◽  
Dengchao Zhang ◽  
Yingshuang Li

AbstractIn this work, we modified nylon 6 with liquid rubber by in-situ polymerization. The infrared analysis suggested that HDI urea diketone is successfully blocked by caprolactam after grafting on hydroxyl of HTPB, and the rubber-modified nylon copolymer is generated by the anionic polymerization. The impact section analysis indicated the rubber-modified nylon 6 resin exhibited an alpha crystal form.With an increase in the rubber content, nylon 6 was more likely to generate stable α crystal. Avrami equation was a good description of the non-isothermal crystallization kinetics of nylon-6 and rubber-modified nylon-6 resin. Moreover, it is found that the initial crystallization temperature of nylon-6 chain segment decreased due to the flexible rubber chain segment. n value of rubber-modified nylon-6 indicated that its growth was the coexistence of two-dimensional discoid and three-dimensional spherulite growth. Finally, the addition of the rubber accelerated the crystallization rate of nylon 6.


Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3583
Author(s):  
Bartosz Opitek ◽  
Janusz Lelito ◽  
Michał Szucki ◽  
Grzegorz Piwowarski ◽  
Łukasz Gondek ◽  
...  

The aim of this study was to analyze the crystallization of the Mg72Zn24Ca4 metallic glass alloy. The crystallization process of metallic glass Mg72Zn24Ca4 was investigated by means of the differential scanning calorimetry. The glass-forming ability and crystallization are both strongly dependent on the heating rate. The crystallization kinetics, during the isothermal annealing, were modelled by the Johnson–Mehl–Avrami equation. Avrami exponents were from 2.7 to 3.51, which indicates diffusion-controlled grain growth. Local exponents of the Johnson–Mehl–Avrami equation were also calculated. In addition, the Mg phase—being the isothermal crystallization product—was found, and the diagram of the time–temperature phase transformation was developed. This diagram enables the reading of the start and end times of the crystallization process, occurring in amorphous ribbons of the Mg72Zn24Ca4 alloy on the isothermal annealing temperature. The research showed high stability of the amorphous structure of Mg72Zn24Ca4 alloy at human body temperature.


1989 ◽  
Vol 281 (5) ◽  
pp. 336-341 ◽  
Author(s):  
W. Stolz ◽  
K. Scharffetter ◽  
W. Abmayr ◽  
W. K�ditz ◽  
T. Krieg

1994 ◽  
Vol 347 ◽  
Author(s):  
J.Ch. Bolomey ◽  
G. Cottard ◽  
P. Berthaud ◽  
A. Lemaitre ◽  
J. F. Portala

ABSTRACTMicrowave multiport sensors have been shown to provide some unique capabilities to achieve real-time testing of products conveyed at high speed. In many applications, quantitative measurements of physical quantities such as moisture content, density, etc… are required, either to guarantee reliable production or to optimally control a fabrication/transformation process. In this paper, different ways of extracting such physical quantities from microwave measurements performed by multiport sensors are presented. Model approaches are used, based on polynomial expansions of the physical quantities to be measured as a function of the microwave amplitude and phase data. Calibration procedures have been investigated for both paper and wood material samples. Comparisons between in-situ, microwave and conventional, measurements are analysed.


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