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Título:	An integrated view of theiInfluence of temperature, pressure, and humidity on the stability of trimorphic cysteamine hydrochloride
Autor/a:	Gana, Inès; Barrio Casado, María del; Ghaddar, Carine; Nicolai, Beatrice; Do, Bernard; Tamarit Mur, José Luis; Safta, Fathi; Rietveld, Ivo B.
Otros autores:	Universitat Politècnica de Catalunya. Departament de Física; Universitat Politècnica de Catalunya. GCM - Grup de Caracterització de Materials
Abstract:	Understanding 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.
Materia(s):	-Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Farmacologia -Àrees temàtiques de la UPC::Física::Termodinàmica -Àrees temàtiques de la UPC::Física::Electromagnetisme::Raigs X -Drugs -- Research -Thermodynamics -Cysteamine hydrochloride -Crystalline trimorphism -Phase diagram -Phase stability -Enantiotropic phase relationship -Thermal expansion -Intermolecular interactions -Hygroscopic -Eutectic -Flame photometric detection -Thermal-expansion tensor -Gas-chromatography -Dichotomy method -State diagram -Powder -Polymorphism -Phase -Coordination -Crystals -Farmàcia--Investigació -Termodinàmica
Derechos:	http://creativecommons.org/licenses/by-nc-nd/3.0/es/
Tipo de documento:	Artículo - Versión presentada Artículo
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