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dc.contributor.authorGana, Inès
dc.contributor.authorBarrio Casado, María del
dc.contributor.authorGhaddar, Carine
dc.contributor.authorNicolai, Beatrice
dc.contributor.authorDo, Bernard
dc.contributor.authorTamarit Mur, José Luis
dc.contributor.authorSafta, Fathi
dc.contributor.authorRietveld, Ivo B.
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament de Física
dc.date.accessioned2015-11-26T11:32:09Z
dc.date.available2016-07-06T00:30:30Z
dc.date.issued2015-07-01
dc.identifier.citationGana, I., Del Barrio, M., Ghaddar, C., Nicolai, B., Do, B., Tamarit, J. Ll., Safta, F., Rietveld, I. An integrated view of theiInfluence of temperature, pressure, and humidity on the stability of trimorphic cysteamine hydrochloride. "Molecular pharmaceutics", 01 Juliol 2015, vol. 12, núm. 7, p. 2276-2288.
dc.identifier.issn1543-8384
dc.identifier.urihttp://hdl.handle.net/2117/79953
dc.description.abstractUnderstanding the phase behavior of pharmaceuticals is important for dosage form development and regulatory requirements, in particular after the incident with ritonavir. In the present paper, a comprehensive study of the solid-state phase behavior of cysteamine hydrochloride used in the treatment of nephropathic cystinosis and recently granted orphan designation by the European Commission is presented employing (high-pressure) calorimetry, water vapor sorption, and X-ray diffraction as a function of temperature. A new crystal form (I2/a, form III) has been discovered, and its structure has been solved by X-ray powder diffraction, while two other crystalline forms are already known. The relative thermodynamic stabilities of the commercial form I and of the newly discovered form III have been established; they possess an overall enantiotropic phase relationship, with form I stable at room temperature and form III stable above 37 degrees C. Its melting temperature was found at 67.3 +/- 0.5 degrees C. Cysteamine hydrochloride is hygroscopic and immediately forms a concentrated saturated solution in water with a surprisingly high concentration of 47.5 mol % above a relative humidity of 35%. No hydrate has been observed. A temperature composition phase diagram is presented that has been obtained with the unary pressure temperature phase diagram, measurements, and calculations. For development, form I would be the best form to use in any solid dosage form, which should be thoroughly protected against humidity.
dc.format.extent13 p.
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Ciències de la salut::Medicina::Farmacologia
dc.subjectÀrees temàtiques de la UPC::Física::Termodinàmica
dc.subjectÀrees temàtiques de la UPC::Física::Electromagnetisme::Raigs X
dc.subject.lcshDrugs -- Research
dc.subject.lcshThermodynamics
dc.subject.otherCysteamine hydrochloride
dc.subject.otherCrystalline trimorphism
dc.subject.otherPhase diagram
dc.subject.otherPhase stability
dc.subject.otherEnantiotropic phase relationship
dc.subject.otherThermal expansion
dc.subject.otherIntermolecular interactions
dc.subject.otherHygroscopic
dc.subject.otherEutectic
dc.subject.otherFlame photometric detection
dc.subject.otherThermal-expansion tensor
dc.subject.otherGas-chromatography
dc.subject.otherDichotomy method
dc.subject.otherState diagram
dc.subject.otherPowder
dc.subject.otherPolymorphism
dc.subject.otherPhase
dc.subject.otherCoordination
dc.subject.otherCrystals
dc.titleAn integrated view of theiInfluence of temperature, pressure, and humidity on the stability of trimorphic cysteamine hydrochloride
dc.typeArticle
dc.subject.lemacFarmàcia--Investigació
dc.subject.lemacTermodinàmica
dc.contributor.groupUniversitat Politècnica de Catalunya. GCM - Grup de Caracterització de Materials
dc.identifier.doi10.1021/mp500830n
dc.rights.accessOpen Access
drac.iddocument16843850
dc.description.versionPostprint (author's final draft)
upcommons.citation.authorGana, I., Del Barrio, M., Ghaddar, C., Nicolai, B., Do, B., Tamarit, J. Ll., Safta, F., Rietveld, I.
upcommons.citation.publishedtrue
upcommons.citation.publicationNameMolecular pharmaceutics
upcommons.citation.volume12
upcommons.citation.number7
upcommons.citation.startingPage2276
upcommons.citation.endingPage2288


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