Plasticization of a Stiff Pharmaceutical Solid for Better Tabletability via Cocrystallization: Shape Synthons as Supramolecular Protecting Groups

Amit Mondal; Biswajit Bhattacharya; Hongbo Chen; Somayeh Khazaei; Susobhan Das; Surojit Bhunia; Somnath Dey; Rituparno Chowdhury; Manjima Bhattacharya; Alexandre Tkatchenko; Lewis L. Stevens; Changquan Calvin Sun; C. Malla Reddy

doi:10.1016/j.cherd.2024.08.042

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Plasticization of a Stiff Pharmaceutical Solid for Better Tabletability via Cocrystallization: Shape Synthons as Supramolecular Protecting Groups

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Plasticization of a Stiff Pharmaceutical Solid for Better Tabletability via Cocrystallization: Shape Synthons as Supramolecular Protecting Groups

Amit Mondal, Biswajit Bhattacharya, Hongbo Chen, Somayeh Khazaei, Susobhan Das, Surojit Bhunia, Somnath Dey, Rituparno Chowdhury, Manjima Bhattacharya, Alexandre Tkatchenko, …

Chemical engineering research & design, Vol.210, pp.506-512

09/2024

DOI: 10.1016/j.cherd.2024.08.042

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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

Mechanical Properties

pharmaceutical drug

stiffness

supramolecular synthons

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, India
Biswajit Bhattacharya - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India
Hongbo Chen - University of Minnesota
Somayeh Khazaei - University of Luxembourg
Susobhan Das - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India
Surojit Bhunia - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India
Somnath Dey - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India
Rituparno Chowdhury - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India
Manjima Bhattacharya - Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India
Alexandre Tkatchenko - University of Luxembourg
Lewis L. Stevens - University of Iowa
Changquan Calvin Sun - University of Minnesota
C. 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
Publisher: Elsevier Ltd
DOI: 10.1016/j.cherd.2024.08.042
ISSN: 0263-8762
eISSN: 1744-3563
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
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984702560302771

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