Journal article
Plasticization of a Stiff Pharmaceutical Solid for Better Tabletability via Cocrystallization: Shape Synthons as Supramolecular Protecting Groups
Chemical engineering research & design, Vol.210, pp.506-512
10/2024
DOI: 10.1016/j.cherd.2024.08.042
Abstract
Extremely high particle stiffness and very low hardness is a serious concern in various mechanical processes in pharmaceutical manufacturing. Here we report an exceptionally high Young’s modulus (E) of ~ 18GPa in a drug, isoniazid (INH). This is one of the highest experimentally determined values among all reported pharmaceutical molecular crystals, which we attribute to the presence of a strong three-dimensional (3D) hydrogen bonding network (HBN). Further, we successfully reduced the 3D HBN in INH to 2D in its cocrystal using a co-former, 3,4-dimethylbenzoic acid (DMBA), where its two hydrophobic groups act like protecting groups at supramolecular level and prevent the extension of HBN. This reduced the E in the 1:1 cocrystal, INH-DMBA, by many folds and markedly improved its powder tabletability. To the best of our knowledge, this is the first reliable molecular level approach to alter the stiffness of pharmaceutical crystals and tabletability improvement in a predictable manner, hence, is important in the context of crystal engineering.
•High Young’s modulus (E) of ~ 18GPa in a drug, isoniazid (INH) crystals•Presence of strong 3D hydrogen bonding network (HBN) imparts high stiffness in INH•Weak dispersive van der Waals (vdW) -Me groups as supramolecular protecting groups•Crystal engineering concept of using shape synthons to avert the formation of 3D HBN•Molecular level alteration of stiffness of API crystals and improvement of tabletability
Details
- Title: Subtitle
- Plasticization of a Stiff Pharmaceutical Solid for Better Tabletability via Cocrystallization: Shape Synthons as Supramolecular Protecting Groups
- Creators
- Amit Mondal - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, IndiaBiswajit Bhattacharya - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, IndiaHongbo Chen - University of MinnesotaSomayeh Khazaei - University of LuxembourgSusobhan Das - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, IndiaSurojit Bhunia - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, IndiaSomnath Dey - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, IndiaRituparno Chowdhury - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, IndiaManjima Bhattacharya - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, IndiaAlexandre Tkatchenko - University of LuxembourgLewis L. Stevens - University of IowaChangquan Calvin Sun - University of MinnesotaC. Malla Reddy - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India
- Resource Type
- Journal article
- Publication Details
- Chemical engineering research & design, Vol.210, pp.506-512
- DOI
- 10.1016/j.cherd.2024.08.042
- ISSN
- 0263-8762
- eISSN
- 1744-3563
- Publisher
- Elsevier Ltd
- Grant note
- DST, New Delhi for Swarnajayanti Fellowship: DST/SJF/CSA-02/2014-15 SERB: CRG/2021/004992, PDF/2016/000262 SoD (DST-SERB): PDF/2018/002502, SX-1411075 National Sci-ence Foundation: IIP-2137264
CMR thanks DST, New Delhi for Swarnajayanti Fellowship (DST/SJF/CSA-02/2014-15) and SERB for funding (No: CRG/2021/004992) . Fellowships for BB (DST-SERB: PDF/2016/000262) , AM (IISER-K) , SuD (CSIR) , SB (DST-INSPIRE) , SoD (DST-SERB: PDF/2018/002502) and RC (KVPY, SX-1411075) are acknowledged. CCS thanks the National Sci-ence Foundation for support through the Industry University Collabo-rative Research Center (IUCRC) grant IIP-2137264, Center for Integrated Materials Science and Engineering for Pharmaceutical Products (CIMSEPP) .
- Language
- English
- Electronic publication date
- 09/2024
- Date published
- 10/2024
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984702560302771
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