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

Autori
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

Izvornik
ACS Sustainable Chemistry & Engineering (2168-0485) 7 (2019), 7; 7102-7110

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

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

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Kemijsko inženjerstvo

POVEZANOST RADA