Assessment of tableting properties using infinitesimal quantities of powder medicine II

Urabe, Masaki; Ito, Shusei; Itai, Shigeru; Yuasa, Hiroshi

doi:10.1016/s1773-2247(06)50065-6

“…We solved the crystal structure of II from PXRD data, and the slurry competition experiments were used to establish the thermodynamic relationship with I. The direct tableting of cocrystal polymorphs prepared in the solid-state was assessed to try to account for poor tableting properties of vitamin C. [51][52][53][54] 10 g scale by planetary ball milling. Planetary ball milling was performed by mixing 5.9 g of vitamin C and 4.1 g of nicotinamide in a 50 mL zirconia jar.…”

Section: Introductionmentioning

confidence: 99%

“…We solved the crystal structure of II from PXRD data and the slurry competition experiments were used to establish the thermodynamic relationship with I . The direct tableting of cocrystal polymorphs prepared in the solid-state was assessed to try to account for poor tableting properties of vitamin C. − …”

Section: Introductionmentioning

confidence: 99%

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

Stolar

¹

,

Lukin

²

,

Tireli

³

et al. 2019

ACS Sustainable Chem. Eng.

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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. File list (3) download file view on ChemRxiv Stolar_manuscript_control of cocrystal polymorphism.pdf (1.52 MiB) download file view on ChemRxiv Stolar_SI_control of cocrystal polymorphism.pdf (814.41 KiB) download file view on ChemRxiv TOC.tif (115.72 KiB) Control of pharmaceutical cocrystal polymorphism on various scales by mechanochemistry: transfer from the laboratory batch-to the large-scale extrusion processing

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“…We solved the crystal structure of II from PXRD data, and the slurry competition experiments were used to establish the thermodynamic relationship with I. The direct tableting of cocrystal polymorphs prepared in the solid-state was assessed to try to account for poor tableting properties of vitamin C. [51][52][53][54]…”

Section: Introductionmentioning

confidence: 99%

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

Stolar¹,

Lukin²,

Tireli³

et al. 2018

Preprint

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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.

show abstract

“…We solved the crystal structure of II from PXRD data, and the slurry competition experiments were used to establish the thermodynamic relationship with I. The direct tableting of cocrystal polymorphs prepared in the solid-state was assessed to try to account for poor tableting properties of vitamin C. [51][52][53][54] Reactants were gently premixed in a beaker and fed manually through the first feed port.…”

Section: Introductionmentioning

confidence: 99%

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

Stolar

¹

,

Lukin²,

Tireli³

et al. 2018

Preprint

0

View full text Add to dashboard Cite

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.

show abstract

Assessment of tableting properties using infinitesimal quantities of powder medicine II

Cited by 6 publications

References 17 publications

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

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

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

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

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