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Challenges and opportunities of pharmaceutical cocrystals: a focused review on non-steroidal anti-inflammatory drugs - PubMed

  • ️Fri Jan 01 2021

Review

. 2021 Feb 9;12(5):705-721.

doi: 10.1039/d0md00400f. eCollection 2021 May 26.

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Review

Challenges and opportunities of pharmaceutical cocrystals: a focused review on non-steroidal anti-inflammatory drugs

Utsav Garg et al. RSC Med Chem. 2021.

Abstract

The focus of the review is to discuss the relevant and essential aspects of pharmaceutical cocrystals in both academia and industry with an emphasis on non-steroidal anti-inflammatory drugs (NSAIDs). Although cocrystals have been prepared for a plethora of drugs, NSAID cocrystals are focused due to their humongous application in different fields of medication such as antipyretic, anti-inflammatory, analgesic, antiplatelet, antitumor, and anti-carcinogenic drugs. The highlights of the review are (a) background of cocrystals and other solid forms of an active pharmaceutical ingredient (API) based on the principles of crystal engineering, (b) why cocrystals are an excellent opportunity in the pharma industry, (c) common methods of preparation of cocrystals from the lab scale to bulk quantity, (d) some latest case studies of NSAIDs which have shown better physicochemical properties for example; mechanical properties (tabletability), hydration, solubility, bioavailability, and permeability, and (e) latest guidelines of the US FDA and EMA opening new opportunities and challenges.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Different applications of cocrystals in drugs and materials.
Fig. 2
Fig. 2. Different solid forms of pharmaceuticals for an API.
Fig. 3
Fig. 3. Different crystalline solid forms.
Fig. 4
Fig. 4. Pictorial representation of different crystalline solid forms: (a) solvates/hydrates, (b) salts, (c) solvates/hydrates of salts, (d) molecular cocrystals (MCCs), (e) solvates/hydrates of MCCs, (f) ionic cocrystals (ICCs), (g) solvates/hydrates of ICCs and (h) polymorphs.
Fig. 5
Fig. 5. Common methods for the preparation of pharmaceutical cocrystals.
Fig. 6
Fig. 6. Molecular structures of (a) naproxen (NIP) and (b) nicotinamide (NIC). (c) Powder compaction properties of NAP, NIC, and 1 : 1 cocrystal. Reproduced with permission from ref. . Copyright 2018 The Springer (American Association of Pharmaceutical Scientists).
Fig. 7
Fig. 7. Molecular structures of (a) metformin (MET) and (b) salicylic acid (SAL). (c) Thermal ellipsoid drawing of the asymmetric unit of the MET–SAL cocrystal. (d) Tabletability profile of MET, SAL, and MET : SAL cocrystal. Reproduced with permission from ref. Copyright 2020 The Elsevier B.V.
Fig. 8
Fig. 8. Molecular structures of (a) piroxicam (PXC) and (b) clonixin (CNX). (c) Thermal ellipsoid drawing of the asymmetric unit of PXC–CNX–solvent (solvent molecule is omitted here for clarity). (d) Color changes of CNX form I, PXC form α2, and PXC–CNX–EA at different time intervals during the moisture stability tests. (e) Powder XRD patterns of CNX, PXC, and PXC–CNX–EA before and after equilibration at 95% RH/25 °C for different periods; simulated powder XRD pattern of PXC·H2O is also provided. Reproduced with permission from ref. . Copyright 2019 The Royal Society of Chemistry.
Fig. 9
Fig. 9. Molecular structures of (a) rac-tramadol hydrochloride and (b) celecoxib. (c) Thermal ellipsoid drawing of the asymmetric unit of CTC. (d) Release (amount versus time) of CTC in water at 37 °C in comparison to tramadol·HCl and celecoxib. Reproduced with permission from ref. . Copyright 2017 The American Chemical Society.
Fig. 10
Fig. 10. Molecular structures of (a) indomethacin (INC) and (b) proline (PL). (c) Thermal ellipsoid drawing of the asymmetric unit of the INC–PL–H2O cocrystal. (d) Solubility comparisons of INC, the cocrystal, and the physical mixture of INC and PL in pH buffers 1.2, 4.0, and 6.8. (e) Plots of flux for INC and the cocrystal with respect to time. (f) Cumulative amount of INC and the cocrystal permeated vs. time. Reproduced with permission from ref. . Copyright 2020 The Royal Society of Chemistry.
Fig. 11
Fig. 11. (a) Thermal ellipsoid drawing of the asymmetric unit of the ZMD-2,4-DHB cocrystal. (b) Solubility comparisons of ZMD and its cocrystal polymorphs, form-I and form-II at pH 1.2 and 7.4 phosphate buffer solutions. Permeability rate% (c) at pH 1.2 and (d) at pH 7.4 phosphate buffer solutions. Flux density (e) at pH 1.2 and (f) at pH 7.4 phosphate buffer solutions. Reproduced with permission from ref. Copyright 2018 The American Chemical Society.
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Utsav Garg
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Yasser Azim

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