The University of Southampton
University of Southampton Institutional Repository

Cocrystals of leflunomide: Design, structural and physicochemical evaluation

Cocrystals of leflunomide: Design, structural and physicochemical evaluation
Cocrystals of leflunomide: Design, structural and physicochemical evaluation
The use of cocrystallisation as a tool to improve the pharmaceutical profile of the low-solubility drug leflunomide, used in the treatment of arthritis, is herein evaluated. Judicious selection of coformers based upon knowledge-based strategy and crystal engineering principles has resulted in new cocrystals with pyrogallol, 3-hydroxybenzoic acid, 2-picolinic acid, and 2-aminopyrimidine. Characterisation and structure determination of these systems was performed using X-ray diffraction. Crystal structure analysis revealed that the hydrogen bonding in the crystal structures corroborate well with the knowledge-based prediction tool. Physicochemical properties such as thermal behaviour, stability, solubility, and dissolution rate of the pharmaceutically acceptable cocrystals were evaluated to assess their impact on the pharmaceutical profile of leflunomide. When compared with their parent compound leflunomide and the physical mixtures, cocrystals were found to exhibit improved physicochemical properties, showing their potential for development of new solid dosage forms.
1528-7483
3923-3933
Cadden, Joseph
86c93935-5d3e-4c0c-bd73-af51f60c9d1c
Klooster, Wim
64dc0111-f415-4226-9189-45764c0933d9
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Aitipamula, Srinivasulu
e1ca2522-d14f-4f82-89ab-1996a021582a
Cadden, Joseph
86c93935-5d3e-4c0c-bd73-af51f60c9d1c
Klooster, Wim
64dc0111-f415-4226-9189-45764c0933d9
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Aitipamula, Srinivasulu
e1ca2522-d14f-4f82-89ab-1996a021582a

Cadden, Joseph, Klooster, Wim, Coles, Simon J. and Aitipamula, Srinivasulu (2019) Cocrystals of leflunomide: Design, structural and physicochemical evaluation. Crystal Growth & Design, 9 (7), 3923-3933. (doi:10.1021/acs.cgd.9b00335).

Record type: Article

Abstract

The use of cocrystallisation as a tool to improve the pharmaceutical profile of the low-solubility drug leflunomide, used in the treatment of arthritis, is herein evaluated. Judicious selection of coformers based upon knowledge-based strategy and crystal engineering principles has resulted in new cocrystals with pyrogallol, 3-hydroxybenzoic acid, 2-picolinic acid, and 2-aminopyrimidine. Characterisation and structure determination of these systems was performed using X-ray diffraction. Crystal structure analysis revealed that the hydrogen bonding in the crystal structures corroborate well with the knowledge-based prediction tool. Physicochemical properties such as thermal behaviour, stability, solubility, and dissolution rate of the pharmaceutically acceptable cocrystals were evaluated to assess their impact on the pharmaceutical profile of leflunomide. When compared with their parent compound leflunomide and the physical mixtures, cocrystals were found to exhibit improved physicochemical properties, showing their potential for development of new solid dosage forms.

Text
Accepted Manuscript - Accepted Manuscript
Restricted to Repository staff only until 31 May 2020.
Request a copy

More information

Accepted/In Press date: 31 May 2019
e-pub ahead of print date: 31 May 2019
Published date: 3 July 2019

Identifiers

Local EPrints ID: 431730
URI: https://eprints.soton.ac.uk/id/eprint/431730
ISSN: 1528-7483
PURE UUID: 3f29c02e-c674-4f75-9032-c8cd336433f6
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

Catalogue record

Date deposited: 14 Jun 2019 16:30
Last modified: 31 Jul 2019 00:47

Export record

Altmetrics

Contributors

Author: Joseph Cadden
Author: Wim Klooster
Author: Simon J. Coles ORCID iD
Author: Srinivasulu Aitipamula

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×