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Solubility behavior and solution chemistry of indomethacin cocrystals in organic solvents
Luleå University of Technology, Department of Health Sciences, Medical Science.ORCID iD: 0000-0002-6050-0432
Department of Pharmaceutical Chemistry, Uppsala University.
Department of Pharmaceutical Sciences, University of Michigan.
Luleå University of Technology, Department of Health Sciences, Medical Science.ORCID iD: 0000-0002-0654-5410
2011 (English)In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 11, no 9, p. 3923-3929Article in journal (Refereed) Published
Abstract [en]

The main objective of this study was to investigate the solubility behavior and solution chemistry of indomethacin-saccharin (IND-SAC) cocrystals in organic media. We also evaluated previously proposed models of cocrystal solubility in organic solvents. In addition, the solubility behavior of IND-SAC cocrystals was compared with that of indomethacin-nicotinamide (IND-NIC) cocrystals using the eutectic constant approach. Phase solubility diagrams of IND-SAC cocrystals in various solvents were generated and the transition concentrations, at which drug and cocrystals are in equilibrium with the solvents, were determined. The solubility of IND-SAC cocrystals was explained by the solubility product and solution complexation. The tested models were found to fit the experimental data and to adequately explain the solubility behavior of the cocrystals. The solution complexation of IND and SAC is negligible in ethyl acetate and low in methanol and ethanol. The IND-NIC cocrystals were more soluble than the IND-SAC cocrystals in all the solvents studied. The eutectic constants predicted both the solubility and the stability of the cocrystals. Understanding the solubility behavior and solution chemistry of cocrystals has important implications for the screening, scale-up, and formulation development of this solid form. Further, the determination of eutectic constants is a simple and resource sparing means of obtaining key information on cocrystal stability and solution behavior

Place, publisher, year, edition, pages
2011. Vol. 11, no 9, p. 3923-3929
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Other Health Sciences
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Health Science
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URN: urn:nbn:se:ltu:diva-13411DOI: 10.1021/cg200517rISI: 000294647600039Scopus ID: 2-s2.0-80052549130Local ID: ca34a56f-28cd-43d8-a977-0c0975201a5fOAI: oai:DiVA.org:ltu-13411DiVA, id: diva2:986364
Note
Validerad; 2011; 20110922 (andbra)Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2018-07-10Bibliographically approved

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Alhalaweh, AmjadVelaga, Sitaram

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