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Thermodynamic stability analysis of tolbutamide polymorphs and solubility in organic solvents

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dc.contributor.author Svärd, Michael
dc.contributor.author Valavi, Masood
dc.contributor.author Khamar, Dikshitkumar
dc.contributor.author Kuhs, Manuel
dc.contributor.author Rasmuson, Åke C.
dc.date.accessioned 2018-10-15T15:22:10Z
dc.date.available 2018-10-15T15:22:10Z
dc.date.issued 2016
dc.identifier.uri http://hdl.handle.net/10344/7230
dc.description peer-reviewed en_US
dc.description.abstract Melting temperatures and enthalpies of fusion have been determined by differential scanning calorimetry (DSC) for 2 polymorphs of the drug tolbutamide: FIH and FV. Heat capacities have been determined by temperature-modulated DSC for 4 polymorphs: FIL, FIH, FII, FV, and for the supercooled melt. The enthalpy of fusion of FII at its melting point has been estimated from the enthalpy of transition of FII into FIH through a thermodynamic cycle. Calorimetric data have been used to derive a quantitative polymorphic stability relationship between these 4 polymorphs, showing that FII is the stable polymorph below approximately 333 K, above which temperature FIH is the stable form up to its melting point. The relative stability of FV is well below the other polymorphs. The previously reported kinetic reversibility of the transformation between FIL and FIH has been verified using in situ Raman spectroscopy. The solid-liquid solubility of FII has been gravimetrically determined in 5 pure organic solvents ( methanol, 1-propanol, ethyl acetate, acetonitrile, and toluene) over the temperature range 278 to 323 K. The ideal solubility has been estimated from calorimetric data, and solution activity coefficients at saturation in the 5 solvents determined. All solutions show positive deviation from Raoult's law, and all van't Hoff plots of solubility data are nonlinear. The solubility in toluene is well below that observed in the other investigated solvents. Solubility data have been correlated and extrapolated to the melting point using a semiempirical regression model. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved. en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries Journal of Pharmaceutical Sciences;105 (6), pp. 1901-1906
dc.relation.uri https://doi.org/10.1016/j.xphs.2016.03.021
dc.rights This is the author’s version of a work that was accepted for publication in Journal of Pharmaceutical Sciences. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Pharmaceutical Sciences, 2016 , 105 (6), pp. 1901-1906, https://doi.org/10.1016/j.xphs.2016.03.021 en_US
dc.subject polymorph en_US
dc.subject solubility en_US
dc.subject thermodynamics en_US
dc.subject FTIR en_US
dc.subject Raman spectroscopy en_US
dc.subject crystal polymorphism en_US
dc.subject calorimetry (DSC) en_US
dc.subject activity coefficient en_US
dc.subject transformation en_US
dc.title Thermodynamic stability analysis of tolbutamide polymorphs and solubility in organic solvents en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2018-10-15T15:06:21Z
dc.description.version ACCEPTED
dc.identifier.doi 10.1016/j.xphs.2016.03.021
dc.identifier.doi 10.1016/j.xphs.2016.03.021
dc.contributor.sponsor SFI en_US
dc.contributor.sponsor Swedish Research Council en_US
dc.relation.projectid 12/RC/2275 en_US
dc.relation.projectid 621-2010-5391 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 1647262
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle Journal Of Pharmaceutical Sciences
dc.description.status peer-reviewed


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