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Evaluation of Cocrystallization Outcomes of Multicomponent Adducts: Rapid Fabrication to Achieve Uniform Particle Size Distribution Using Thermal Inkjet Printing

Seera, R and Guru Row, TN (2020) Evaluation of Cocrystallization Outcomes of Multicomponent Adducts: Rapid Fabrication to Achieve Uniform Particle Size Distribution Using Thermal Inkjet Printing. In: Crystal Growth and Design, 20 (7). pp. 4667-4677.

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Official URL: https://dx.doi.org/10.1021/acs.cgd.0c00469

Abstract

Multicomponent adducts such as cocrystals and eutectics have become an integral part of the pharmaceutical industry since the application potential of such products is imminent in drug design and fabrication. Cocrystallization of metronidazole, an antibiotic antiprotozoal drug, belonging to the family of nitro-imidazole, with benzoic acid and mono-, di-, tri-, hydroxybenzoic acids results in multicomponent adducts with better physicochemical properties than the drug. Cocrystallization experiments using liquid assisted grinding (LAG), melt cool, and routine solvent evaporation yielded eutectics except for the combinations 3,5-dihydroxy and 3,4,5-trihydroxybenzoic acids, which produce cocrystals. The products have been characterized and analyzed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In particular, the structures of the cocrystals were determined using single crystal X-ray diffraction, whereas those of the eutectics were identified based on PXRD, DSC, and binary phase diagram construction. Using well-known thermal inkjet printing (TIJP), organic solutions of metronidazole and substituted hydroxybenzoic acids were injected into a cartridge and printed onto the template via a jet dispensing mechanism by varying the drug-coformer stoichiometric ratio to generate the cocrystals and eutectics of the adducts in quick time. The products formed from inkjet printing show excellent consistency in the particle size distribution and can be easily subjected to scaling up in industry compared to those prepared using the conventional cocrystallization techniques such as slurry grinding, rotavapor, and routine solution evaporation, which are time-consuming and produce varying particle sizes, which is a hindrance to product development and scaling during mass production. © 2020 American Chemical Society.

Item Type: Journal Article
Publication: Crystal Growth and Design
Publisher: American Chemical Society
Additional Information: Copy right for this article belongs to American Chemical Society
Keywords: Benzoic acid; Differential scanning calorimetry; Drug products; Eutectics; Evaporation; Fabrication; Grinding (machining); Ink jet printing; Light transmission; Particle size; Physicochemical properties; Product design; Scanning electron microscopy; Single crystals; Size distribution; Solidification; Thermal printing; Thermogravimetric analysis; X ray diffraction, Binary phase diagrams; Hydroxybenzoic acids; Pharmaceutical industry; Powder X-ray diffraction (pXRD); Single crystal x-ray diffraction; Solution evaporation; Solvent evaporation; Stoichiometric ratio, Particle size analysis
Department/Centre: Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited: 13 Nov 2020 11:01
Last Modified: 13 Nov 2020 11:01
URI: http://eprints.iisc.ac.in/id/eprint/66095

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