Exploring polymorphism and stoichiometric diversity in naproxen/proline cocrystals

Tumanova, Natalia; Tumanov, Nikolay; Fischer, Friedrich; Morelle, Fabrice; Ban, Voraksmy; Robeyns, Koen; Filinchuk, Yaroslav; Emmerling, Franziska; Leyssens, Tom

doi:10.1039/c8ce01338a

Cited by 28 publications

(24 citation statements)

References 64 publications

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“…The APIs include naproxen (containing a carboxyl group), levetiracetam (containing two amide groups), oxiracetam (containing two amide groups and a hydroxyl group), and diprophylline (a xanthine derivative, similar to caffeine and theophylline), but only naproxen was capable of forming a co-crystal with amino acids [ 76 ]. Next, they also developed naproxen- l -proline co-crystal as a potential zwitterionic co-crystal [ 81 ]. The same result was found by Nugrahani et al, who examined l -proline co-crystal formation with three API, i.e., mefenamic acid, ketoprofen, and diclofenac acid.…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

“…Co-crystallization with the amino acid l -proline has been widely applied to increase the solubility of NSAID, mostly with low solubilities, such as naproxen [ 81 , 86 , 91 ], diclofenac acid [ 92 ], and ibuprofen [ 20 ], whose zwitterionic co-crystal structure has been investigated. It showed the ability to form co-crystals with several amino acids, such as alanine, tryptophan, tyrosine [ 20 ], and arginine [ 93 , 94 ].…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

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Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Nugrahani

Jessica

2021

Molecules

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Co-crystals are one of the most popular ways to modify the physicochemical properties of active pharmaceutical ingredients (API) without changing pharmacological activity through non-covalent interactions with one or more co-formers. A “green method” has recently prompted many researchers to develop solvent-free techniques or minimize solvents for arranging the eco-friendlier process of co-crystallization. Researchers have also been looking for less-risk co-formers that produce the desired API’s physicochemical properties. This review purposed to collect the report studies of amino acids as the safe co-former and explored their advantages. Structurally, amino acids are promising co-former candidates as they have functional groups that can form hydrogen bonds and increase stability through zwitterionic moieties, which support strong interactions. The co-crystals and deep eutectic solvent yielded from this natural compound have been proven to improve pharmaceutical performance. For example, l-glutamine could reduce the side effects of mesalamine through an acid-base stabilizing effect in the gastrointestinal fluid. In addition, some amino acids, especially l-proline, enhances API’s solubility and absorption in its natural deep eutectic solvent and co-crystals systems. Moreover, some ionic co-crystals of amino acids have also been designed to increase chiral resolution. Therefore, amino acids are safe potential co-formers, which are suitable for improving the physicochemical properties of API and prospective to be developed further in the dosage formula and solid-state syntheses.

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Section: Amino Acids As Co-formersmentioning

confidence: 99%

Section: Amino Acids As Co-formersmentioning

confidence: 99%

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Nugrahani

Jessica

2021

Molecules

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“…A search for cocrystal structures of PRO gave 148 hits. PRO has been used as a cocrystal former of various active pharmaceutical ingredients (Tilborg et al, 2013;Tumanova et al, 2018;Song et al, 2019). The most relevant cocrystal structure to this work is the cocrystal of RES and PRO (He et al, 2017; refcode PEBZEE).…”

Section: Database Surveymentioning

confidence: 99%

Syntheses and crystal structures of hydrated and anhydrous 1:2 cocrystals of oxyresveratrol and zwitterionic proline

2020

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The hydrated and anhydrous 1:2 cocrystals of oxyresveratrol (4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,3-diol; OXY; C14H12O4) and proline [(S)-pyrrolidine-2-carboxylic acid; PRO; C5H9NO2], namely, 4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,3-diol bis[(S)-pyrrolidin-1-ium-2-carboxylate] monohydrate, C14H12O4·2C5H9NO2·H2O, and the anhydrous form, C14H12O4·2C5H9NO2, were obtained by crystallization at different temperatures. Both of them crystallize with orthorhombic (P212121) symmetry. The structures display N—H...O and O—H...O hydrogen-bonding interactions between PRO and PRO, OXY and OXY, and OXY and PRO. In the hydrated cocrystal, these types of contacts are also observed between the OXY, PRO and water molecules. A combination of these interactions leads to a three-dimensional supramolecular assembly in each case. Hirshfeld surfaces were used to gain further insight into the intermolecular interactions in the packing, including the relative percentage contributions of the significant intermolecular H...H and H...O/O...H contacts.

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“…Of the 117 structures, less than 20 are pharmaceutical cocrystals involving zwitterionic Pro. Some representative examples are celecoxib, niflumic acid, clonixin and diclofenac, and naproxen …”

Section: Introductionmentioning

confidence: 99%

“…Some representative examples are celecoxib, 20 niflumic acid, clonixin and diclofenac, 21 and naproxen. 22 The most common supramolecular synthons established by Pro consist of charge-assisted HBs between the carboxylate and the ammonium groups of Pro or between either of them and a carboxylic moiety of a different molecule (e.g., naproxen, 14 fumaric acid 23 ). Both moieties tend to form interactions with OH groups from alcohols (e.g., dapagliflozin) 24 or phenols (e.g., ezetimibe, 25 quercetin 26 ), while the COO − group is prone to engage in dimeric interactions with molecules displaying two proximal NH (e.g., ureas) 27 or OH (e.g., boronic acids) 27 groups.…”

Section: ■ Introductionmentioning

confidence: 99%

Pseudopolymorphism Driven by Stoichiometry and Hydrated/Anhydrous Reagents: The Riveting Case of Methyl Gallate·l-Proline

Bordignon

Vioglio

Bertoncini

et al. 2021

Crystal Growth & Design

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Among GRAS molecules, α-amino acids have been extensively used to produce molecular salts and cocrystals of APIs thanks to their nontoxicity, ready availability, cheapness, and their zwitterionic nature. Here we report on the use of both anhydrous and hydrated L-proline (Pro and Pro•H 2 O, respectively) with methyl gallate (MG) to selectively obtain by mechanochemical methods anhydrous and hydrated cocrystals: MG•Pro 2 and MG 2 •Pro 2 •H 2 O, respectively. The two new forms were characterized by means of single-crystal and powder X-ray diffraction (SCXRD and PXRD), solid-state nuclear magnetic resonance (SSNMR), DSC, and TGA. Interestingly, the choice of the starting material together with the stoichiometry drives the formation of the cocrystal toward either the anhydrous or the hydrate form: the anhydrous form could be obtained only on starting from anhydrous Pro, whereas the hydrate could be obtained with Pro•H 2 O or with Pro by matching the correct stoichiometry. An energy framework analysis allowed us to rationalize this peculiar water uptake behavior in terms of both the relative interaction strengths of proline− proline, proline−water, and proline−methyl gallate pairs and packing features.

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Exploring polymorphism and stoichiometric diversity in naproxen/proline cocrystals

Abstract: This work studies a multitude of cocrystals obtained by combining chiral and/or racemic naproxen and proline, 17 in total.

Cited by 28 publications

References 64 publications

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Syntheses and crystal structures of hydrated and anhydrous 1:2 cocrystals of oxyresveratrol and zwitterionic proline

Pseudopolymorphism Driven by Stoichiometry and Hydrated/Anhydrous Reagents: The Riveting Case of Methyl Gallate·l-Proline

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