Crystal packing arrangement, chain conformation, and physicochemical properties of gemfibrozil amine salts

Miren Ramirez; Sarah E. David; Carl H. Schwalbe; Kofi Asare-Addo; Barbara R. Conway; Peter Timmins

doi:10.1021/acs.cgd.7b00352

Crystal packing arrangement, chain conformation, and physicochemical properties of gemfibrozil amine salts

Miren Ramirez, Sarah E. David, Carl H. Schwalbe, Kofi Asare-Addo, Barbara R. Conway, Peter Timmins^*

^*Corresponding author for this work

Aston Pharmacy School

Research output: Contribution to journal › Article › peer-review

Abstract

Salt formation is used to optimize pharmaceutical properties for carboxylic acid drugs, but selection can often be empirical. An extended series of salts of the anti-hyperlipidaemia carboxylic acid drug gemfibrozil was prepared using a related series of amine counterions to gain a molecular insight into the impact of crystal packing arrangements on their physicochemical properties. With only a few exceptions, the salts had similar crystal packing motifs. Although there was no discernible relationship between melting point of the salt form and the aqueous solubility of the salt across the whole data set, there were trends within structurally related series of salts relating increasing melting enthalpy with increasing molecular weight of the counterion.

Original language	English
Pages (from-to)	3743-3750
Number of pages	8
Journal	Crystal Growth and Design
Volume	17
Issue number	7
DOIs	https://doi.org/10.1021/acs.cgd.7b00352
Publication status	Published - 13 Jun 2017

Bibliographical note

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.cgd.7b00352

Access to Document

10.1021/acs.cgd.7b00352

Crystal packing arrangement, chain conformation, and physicochemical properties of gemfibrozil amine salts
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.cgd.7b00352
Accepted author manuscript, 1.2 MB

Cite this

@article{661c089ff4ec43268990a2d3885b4c38,

title = "Crystal packing arrangement, chain conformation, and physicochemical properties of gemfibrozil amine salts",

abstract = "Salt formation is used to optimize pharmaceutical properties for carboxylic acid drugs, but selection can often be empirical. An extended series of salts of the anti-hyperlipidaemia carboxylic acid drug gemfibrozil was prepared using a related series of amine counterions to gain a molecular insight into the impact of crystal packing arrangements on their physicochemical properties. With only a few exceptions, the salts had similar crystal packing motifs. Although there was no discernible relationship between melting point of the salt form and the aqueous solubility of the salt across the whole data set, there were trends within structurally related series of salts relating increasing melting enthalpy with increasing molecular weight of the counterion.",

author = "Miren Ramirez and David, {Sarah E.} and Schwalbe, {Carl H.} and Kofi Asare-Addo and Conway, {Barbara R.} and Peter Timmins",

note = "This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright {\textcopyright} American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.cgd.7b00352",

year = "2017",

month = jun,

day = "13",

doi = "10.1021/acs.cgd.7b00352",

language = "English",

volume = "17",

pages = "3743--3750",

journal = "Crystal Growth and Design",

issn = "1528-7483",

publisher = "American Chemical Society",

number = "7",

}

TY - JOUR

T1 - Crystal packing arrangement, chain conformation, and physicochemical properties of gemfibrozil amine salts

AU - Ramirez, Miren

AU - David, Sarah E.

AU - Schwalbe, Carl H.

AU - Asare-Addo, Kofi

AU - Conway, Barbara R.

AU - Timmins, Peter

N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.cgd.7b00352

PY - 2017/6/13

Y1 - 2017/6/13

N2 - Salt formation is used to optimize pharmaceutical properties for carboxylic acid drugs, but selection can often be empirical. An extended series of salts of the anti-hyperlipidaemia carboxylic acid drug gemfibrozil was prepared using a related series of amine counterions to gain a molecular insight into the impact of crystal packing arrangements on their physicochemical properties. With only a few exceptions, the salts had similar crystal packing motifs. Although there was no discernible relationship between melting point of the salt form and the aqueous solubility of the salt across the whole data set, there were trends within structurally related series of salts relating increasing melting enthalpy with increasing molecular weight of the counterion.

AB - Salt formation is used to optimize pharmaceutical properties for carboxylic acid drugs, but selection can often be empirical. An extended series of salts of the anti-hyperlipidaemia carboxylic acid drug gemfibrozil was prepared using a related series of amine counterions to gain a molecular insight into the impact of crystal packing arrangements on their physicochemical properties. With only a few exceptions, the salts had similar crystal packing motifs. Although there was no discernible relationship between melting point of the salt form and the aqueous solubility of the salt across the whole data set, there were trends within structurally related series of salts relating increasing melting enthalpy with increasing molecular weight of the counterion.

UR - http://pubs.acs.org/doi/abs/10.1021/acs.cgd.7b00352

UR - http://www.scopus.com/inward/record.url?scp=85021916877&partnerID=8YFLogxK

U2 - 10.1021/acs.cgd.7b00352

DO - 10.1021/acs.cgd.7b00352

M3 - Article

AN - SCOPUS:85021916877

SN - 1528-7483

VL - 17

SP - 3743

EP - 3750

JO - Crystal Growth and Design

JF - Crystal Growth and Design

IS - 7

ER -

Crystal packing arrangement, chain conformation, and physicochemical properties of gemfibrozil amine salts

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this