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Mechanistic in situ and ex situ studies of phase transformations in molecular co‐crystals

DOI: 10.1002/chem.202002267 DOI Help

Authors: Alexander Clout (University College London (UCL)) , Asma Buanz (University College London (UCL)) , Yuying Pang (University College London) , Wing-Mei Tsui (University College London) , Dongpeng Yan (Beijing Normal University) , Gary Parkinson (University of London) , Timothy Prior (University of Hull) , Dejan-Kresimir Bucar (University College London) , Simon Gaisford (University College London (UCL)) , Gareth Williams (University College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chemistry – A European Journal

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 12735

Open Access Open Access

Abstract: Co‐crystallisation is widely explored as a route to improve the physical properties of pharmaceutical active ingredients, but little is known about the fundamental mechanisms of the process. Here we apply a novel hyphenated differential scanning calorimetry ‐ X‐ray diffraction technique to mimic the commercial hot melt extrusion process, and explore the heat‐induced synthesis of four new co‐crystals containing isonicotinamide. These comprise a 1:1 co‐crystal with 4‐hydroxybenzoic acid, 2:1 and 1:2 systems with 4‐hydroxyphenylacetic acid and a 1:1 crystal with 3,4‐dihydroxyphenylactic acid. The formation of co‐crystals during heating is complex mechanistically. In addition to co‐crystallisation, conversions between polymorphs of the co‐former starting materials and co‐crystal products are also observed. A subsequent study exploring the use of inkjet printing and milling to generate co‐crystals revealed that the synthetic approach has a major effect on the co‐crystal species and polymorphs produced.

Journal Keywords: pharmaceutical co-crystals; differential scanning calorimetry; synchrotron X-ray diffraction; hyphenated techniques

Subject Areas: Chemistry


Instruments: I12-JEEP: Joint Engineering, Environmental and Processing

Added On: 30/07/2020 10:15

Documents:
chem.202002267.pdf

Discipline Tags:

Organic Chemistry Chemistry

Technical Tags:

Diffraction