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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 (CROSBI ID 263507)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Stolar, Tomislav ; Lukin, Stipe ; Tireli, Martina ; Sović, Irena ; Karadeniz, Bahar ; Kereković, Irena ; Matijašić, Gordana ; Gretić, Matija ; Katančić, Zvonimir ; Dejanović, Igor et al. 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 (2019), 7; 7102-7110. doi: 10.1021/acssuschemeng.9b00043

Podaci o odgovornosti

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

engleski

Control of pharmaceutical cocrystal polymorphism on various scales by mechanochemistry: transfer from the laboratory batch to the large-scale extrusion processing

We demonstrate a controllable mechanochem. 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 mechanochem. synthesis, and its crystal structure was detd. from synchrotron powder X-​ray diffraction data. Lab. in situ monitoring by Raman spectroscopy provided direct insight into the cocrystals formation and was further used to optimize the manufg. procedure. Subgram synthesis using a lab. mixer mill was transferred to the 10 g scale on a planetary ball mill and continuous manufg. using a twin-​screw extruder. Both cocrystal polymorphs perform excellently in tableting, thus alleviating the notoriously poor compactible properties of vitamin C, while the mechanochem. cocrystn. does not harm its antioxidant properties.

active pharmaceutical ingredients ; large-scale processing ; mechanochemistry ; polymorphism control ; twin-screw extrusion

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Podaci o izdanju

7 (7)

2019.

7102-7110

objavljeno

2168-0485

10.1021/acssuschemeng.9b00043

Povezanost rada

Kemija, Kemijsko inženjerstvo

Poveznice
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