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.
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
3 July 2019
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), .
(doi:10.1021/acs.cgd.9b00335).
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.
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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: http://eprints.soton.ac.uk/id/eprint/431730
ISSN: 1528-7483
PURE UUID: 3f29c02e-c674-4f75-9032-c8cd336433f6
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Date deposited: 14 Jun 2019 16:30
Last modified: 16 Mar 2024 07:56
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Author:
Joseph Cadden
Author:
Wim Klooster
Author:
Srinivasulu Aitipamula
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