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

Stolar, Tomislav; Lukin, Stipe; Tireli, Martina; Sović, Irena; Karadeniz, Bahar; Kereković, Irena; Matijašić, Gordana; Gretić, Matija; Katančić, Zvonimir; Dejanović, Igor; Michiel, Marco di; Halasz, Ivan; Užarević, Krunoslav (2019) Control of Pharmaceutical Cocrystal Polymorphism on Various Scales by Mechanochemistry: Transfer from the Laboratory Batch to the Large-Scale Extrusion Processing. ACS Sustainable Chemistry & Engineering, 7 (7). pp. 7102-7110. ISSN 2168-0485

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Abstract

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 synchrotron 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. Subgram synthesis using a 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.

Item Type: Article
Uncontrolled Keywords: Mechanochemical synthesis, Pharmaceutical materials, vitamin C, vitamin B3, Twin-screw extrusion, continuous processing
Subjects: NATURAL SCIENCES > Chemistry > Inorganic Chemistry
NATURAL SCIENCES > Chemistry > Applied Chemistry
Divisions: Division of Physical Chemistry
Projects:
Project titleProject leaderProject codeProject type
Mehaniokemijska reaktivnost pod kontroliranim uvjetima temperature i atmosfere za čišću sintezu funkcionalnih materijala-MECHANOCONTROLKrunoslav UžarevićUIP-2014-09-4744HRZZ
Depositing User: Krunoslav Užarević
Date Deposited: 14 Dec 2020 12:26
Last Modified: 14 Dec 2020 12:26
URI: http://fulir.irb.hr/id/eprint/6139
DOI: 10.1021/acssuschemeng.9b00043

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