On the influence of using a zwitterionic coformer for cocrystallization: Structural focus on naproxen-proline cocrystals

A. Tilborg, B. Norberg, J. Wouters, G. Springuel, T. Leyssens

Research output: Contribution to journalArticle

Abstract

Four original cocrystal structures incorporating a zwitterionic amino acid, prolinium, and a therapeutical agent from profen pharmaceutical family, naproxen, are highlighted and characterized in this study. Powder X-ray diffraction and differential scanning calorimetry permits the observation of the formation of the new structures, obtained by liquid-assisted grinding with methanol. Single-crystal X-ray diffraction gives us a precise outlook of the crystalline network, and allows us to accurately determine the main structural supramolecular synthon: column-like motifs, formed by prolinium entities, around whom the pharmaceutical coformer is organized. From comparison with the CSD, a similar structural pattern emerged in several other structures incorporating prolinium moieties, but not in the case of cocrystals incorporating naproxen and other non-zwitterionic coformers. This result leads us to the conclusion that zwitterionic compounds, such as amino acids, can force a pharmaceutical coformer to structure itself following a known common motif guided only by the zwitterionic entity; a very challenging aspect to take into account when developing new solid forms of therapeutical agents.
Original languageEnglish
Pages (from-to)3341-3350
Number of pages10
JournalCrystEngComm
Volume15
Issue number17
DOIs
Publication statusPublished - 7 May 2013

Fingerprint

Naproxen
Proline
Drug products
amino acids
zwitterions
Amino acids
grinding
diffraction
Pharmaceutical Preparations
Amino Acids
x rays
heat measurement
methyl alcohol
X ray powder diffraction
scanning
Methanol
Differential scanning calorimetry
single crystals
liquids
Single crystals

Cite this

@article{5b149d1b80b14a1d8ea1005cc5efb08e,
title = "On the influence of using a zwitterionic coformer for cocrystallization: Structural focus on naproxen-proline cocrystals",
abstract = "Four original cocrystal structures incorporating a zwitterionic amino acid, prolinium, and a therapeutical agent from profen pharmaceutical family, naproxen, are highlighted and characterized in this study. Powder X-ray diffraction and differential scanning calorimetry permits the observation of the formation of the new structures, obtained by liquid-assisted grinding with methanol. Single-crystal X-ray diffraction gives us a precise outlook of the crystalline network, and allows us to accurately determine the main structural supramolecular synthon: column-like motifs, formed by prolinium entities, around whom the pharmaceutical coformer is organized. From comparison with the CSD, a similar structural pattern emerged in several other structures incorporating prolinium moieties, but not in the case of cocrystals incorporating naproxen and other non-zwitterionic coformers. This result leads us to the conclusion that zwitterionic compounds, such as amino acids, can force a pharmaceutical coformer to structure itself following a known common motif guided only by the zwitterionic entity; a very challenging aspect to take into account when developing new solid forms of therapeutical agents.",
author = "A. Tilborg and B. Norberg and J. Wouters and G. Springuel and T. Leyssens",
year = "2013",
month = "5",
day = "7",
doi = "10.1039/c3ce40084k",
language = "English",
volume = "15",
pages = "3341--3350",
journal = "CrystEngComm",
issn = "1466-8033",
publisher = "Royal Society of Chemistry",
number = "17",

}

On the influence of using a zwitterionic coformer for cocrystallization : Structural focus on naproxen-proline cocrystals. / Tilborg, A.; Norberg, B.; Wouters, J.; Springuel, G.; Leyssens, T.

In: CrystEngComm, Vol. 15, No. 17, 07.05.2013, p. 3341-3350.

Research output: Contribution to journalArticle

TY - JOUR

T1 - On the influence of using a zwitterionic coformer for cocrystallization

T2 - Structural focus on naproxen-proline cocrystals

AU - Tilborg, A.

AU - Norberg, B.

AU - Wouters, J.

AU - Springuel, G.

AU - Leyssens, T.

PY - 2013/5/7

Y1 - 2013/5/7

N2 - Four original cocrystal structures incorporating a zwitterionic amino acid, prolinium, and a therapeutical agent from profen pharmaceutical family, naproxen, are highlighted and characterized in this study. Powder X-ray diffraction and differential scanning calorimetry permits the observation of the formation of the new structures, obtained by liquid-assisted grinding with methanol. Single-crystal X-ray diffraction gives us a precise outlook of the crystalline network, and allows us to accurately determine the main structural supramolecular synthon: column-like motifs, formed by prolinium entities, around whom the pharmaceutical coformer is organized. From comparison with the CSD, a similar structural pattern emerged in several other structures incorporating prolinium moieties, but not in the case of cocrystals incorporating naproxen and other non-zwitterionic coformers. This result leads us to the conclusion that zwitterionic compounds, such as amino acids, can force a pharmaceutical coformer to structure itself following a known common motif guided only by the zwitterionic entity; a very challenging aspect to take into account when developing new solid forms of therapeutical agents.

AB - Four original cocrystal structures incorporating a zwitterionic amino acid, prolinium, and a therapeutical agent from profen pharmaceutical family, naproxen, are highlighted and characterized in this study. Powder X-ray diffraction and differential scanning calorimetry permits the observation of the formation of the new structures, obtained by liquid-assisted grinding with methanol. Single-crystal X-ray diffraction gives us a precise outlook of the crystalline network, and allows us to accurately determine the main structural supramolecular synthon: column-like motifs, formed by prolinium entities, around whom the pharmaceutical coformer is organized. From comparison with the CSD, a similar structural pattern emerged in several other structures incorporating prolinium moieties, but not in the case of cocrystals incorporating naproxen and other non-zwitterionic coformers. This result leads us to the conclusion that zwitterionic compounds, such as amino acids, can force a pharmaceutical coformer to structure itself following a known common motif guided only by the zwitterionic entity; a very challenging aspect to take into account when developing new solid forms of therapeutical agents.

UR - http://www.scopus.com/inward/record.url?scp=84875793550&partnerID=8YFLogxK

U2 - 10.1039/c3ce40084k

DO - 10.1039/c3ce40084k

M3 - Article

VL - 15

SP - 3341

EP - 3350

JO - CrystEngComm

JF - CrystEngComm

SN - 1466-8033

IS - 17

ER -