Control of Pharmaceutical Cocrystal Polymorphism on Various Scales by Mechanochemistry: Transfer from the Laboratory Batch- to the Large-Scale Extrusion Processing

<p>We demonstrate a controllable mechanochemical synthesis of cocrystal polymorphs of ascorbic acid (vitamin C) and nicotinamide (vitamin B3) on different scales and without using bulk solvents. Next to the previously described polymorph of the 1:1 cocrystal, which is one of the first cocrystals approved for human consumption, we report here a new, thermodynamically more stable polymorph detected during in situ synchrotron powder X-ray diffraction monitoring of milling reactions. The new polymorph is currently available exclusively by mechanochemical synthesis, and its crystal structure was determined from powder X-ray diffraction data. Laboratory in situ monitoring by Raman spectroscopy provided direct insight into the cocrystals formation and was further used to optimize the manufacturing procedure. Sub-gram synthesis using laboratory mixer mill was transferred to the 10 g scale on a planetary ball mill and continuous manufacturing using a twin-screw extruder. Both cocrystal polymorphs perform excellently in tableting, thus alleviating the notoriously poor compactible properties of vitamin C, while the mechanochemical cocrystallization does not harm its antioxidant properties.<b></b></p>

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In-situ monitoring the inhibiting effect of polyphosphinocarboxylic acid on CaCO3 scale formation by synchrotron X-ray diffraction

Chemical Engineering Science ◽

10.1016/j.ces.2008.09.036 ◽

2009 ◽

Vol 64 (5) ◽

pp. 912-918 ◽

Cited By ~ 19

Author(s):

Tao Chen ◽

Anne Neville ◽

Ken Sorbie ◽

Zhong Zhong

Keyword(s):

Scale Formation ◽

In Situ Monitoring ◽

X Ray Diffraction ◽

X Ray ◽

Inhibiting Effect

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In-situ Monitoring of Laser Surface Line Hardening by Means of Synchrotron X-Ray Diffraction

Residual Stresses 2016 ◽

10.21741/9781945291173-79 ◽

2016 ◽

Cited By ~ 2

Keyword(s):

Laser Surface ◽

In Situ Monitoring ◽

X Ray Diffraction ◽

X Ray

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In-Situ Diffraction Studies of Gas Storage Materials on a Laboratory X-Ray System

MRS Proceedings ◽

10.1557/opl.2013.1080 ◽

2013 ◽

Vol 1544 ◽

Author(s):

Marco Sommariva ◽

Harald van Weeren ◽

Olga Narygina ◽

Jan-André Gertenbach ◽

Christian Resch ◽

...

Keyword(s):

Large Scale ◽

Fossil Fuels ◽

Reaction Chamber ◽

Hydrogen Gas ◽

Gas Pressure ◽

X Ray Diffraction ◽

X Ray ◽

Structural Modifications ◽

Model Studies

ABSTRACTThe sorption processes for hydrogen and carbon dioxide are of considerable, and growing interest, particularly due to their relevance to a society that seeks to replace fossil fuels with a more sustainable energy source. X-ray diffraction allows a unique perspective for studying structural modifications and reaction mechanisms that occur when gas and solid interact. The fundamental challenge associated with such a study is that experiments are conducted while the solid sample is held under a gas pressure. To date in-situ high gas pressure studies of this nature have typically been undertaken at large-scale facilities such as synchrotrons or on dedicated laboratory instruments. Here we report high-pressure XRD studies carried out on a multi-purpose diffractometer. To demonstrate the suitability of the equipment, two model studies were carried out, firstly the reversible hydrogen cycling over LaNi5, and secondly the structural change that occurs during the decomposition of ammonia borane that results in the generation of hydrogen gas in the reaction chamber. The results have been finally compared to the literature. The study has been made possible by the combination of rapid X-ray detectors with a reaction chamber capable of withstanding gas pressures up to 100 bar and temperatures up to 900 °C.

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In situ monitoring of hydrothermal reactions by X-ray diffraction with Bragg–Brentano geometry

Journal of Applied Crystallography ◽

10.1107/s1600576720006019 ◽

2020 ◽

Vol 53 (4) ◽

pp. 1163-1166

Author(s):

Karsten Mesecke ◽

Winfried Malorny ◽

Laurence N. Warr

Keyword(s):

Quantitative Information ◽

In Situ Monitoring ◽

X Ray Diffraction ◽

Hydrothermal Conditions ◽

X Ray ◽

Saturated Vapour Pressure ◽

Concrete Production ◽

Aerated Concrete ◽

Kinetics Of

This note describes an autoclave chamber developed and constructed by Anton Paar and its application for in situ experiments under hydrothermal conditions. Reactions of crystalline phases can be studied by successive in situ measurements on a conventional laboratory X-ray diffractometer with Bragg–Brentano geometry at temperatures <483 K and saturated vapour pressure <2 MPa. Variations in the intensity of X-ray diffraction reflections of both reactants and products provide quantitative information for studying the reaction kinetics of both dissolution and crystal growth. Feasibility is demonstrated by studying a cementitious mixture used for autoclaved aerated concrete production. During a period of 5.7 h at 466 K and 1.35 MPa, the crystallization of torbermorite and the partial consumption of quartz were monitored.

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Inside Back Cover: Real-Time In Situ Powder X-ray Diffraction Monitoring of Mechanochemical Synthesis of Pharmaceutical Cocrystals (Angew. Chem. Int. Ed. 44/2013)

Angewandte Chemie International Edition ◽

10.1002/anie.201308380 ◽

2013 ◽

Vol 52 (44) ◽

pp. 11665-11665

Author(s):

Ivan Halasz ◽

Andreas Puškarić ◽

Simon A. J. Kimber ◽

Patrick J. Beldon ◽

Ana M. Belenguer ◽

...

Keyword(s):

Real Time ◽

Mechanochemical Synthesis ◽

X Ray Diffraction ◽

Pharmaceutical Cocrystals ◽

X Ray ◽

Back Cover

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In Situ Monitoring of Crystallization Processes Using Synchrotron X-ray Diffraction: The Search for Structural Precursors

Crystal Growth & Design ◽

10.1021/cg025514j ◽

2002 ◽

Vol 2 (4) ◽

pp. 269-272 ◽

Cited By ~ 16

Author(s):

Roger J. Davey ◽

Wei Liu ◽

Michael J. Quayle ◽

Gordon J. T. Tiddy

Keyword(s):

In Situ Monitoring ◽

X Ray Diffraction ◽

X Ray

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In Situ Observation of Stress Accumulation during Sub-Merged Arc Welding

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.996.417 ◽

2014 ◽

Vol 996 ◽

pp. 417-423 ◽

Cited By ~ 1

Author(s):

Arne Kromm ◽

Thomas Kannengiesser

Keyword(s):

Arc Welding ◽

Large Scale ◽

X Ray Diffraction ◽

X Ray ◽

Residual Stress State ◽

Testing Facility ◽

Large Scale Testing ◽

The Impact ◽

Stress Accumulation

Results obtained from laboratory tests mostly need to be verified under fabrication conditions in order to incorporate design specifics (joint configuration and restraint), which effect the residual stress state considerably. For this purpose, multi-pass sub merged arc welding was performed in a special large-scale testing facility. The impact of varying interpass temperatures could be proven in-situ by means of a pronounced stress accumulation during welding and subsequent heat treatment accompanied by stress determination using X-ray diffraction.

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