An Integrated View of the Influence of Temperature, Pressure, and Humidity on the Stability of Trimorphic Cysteamine Hydrochloride

Autor: Ivo B. Rietveld, Carine Ghaddar, Bernard Do, Fathi Safta, Béatrice Nicolaï, Inès Gana, Maria Barrio, Josep-Lluís Tamarit
Přispěvatelé: Universitat Politècnica de Catalunya. Departament de Física, Universitat Politècnica de Catalunya. GCM - Grup de Caracterització de Materials
Rok vydání: 2015
Předmět:
Pharmaceutical Science
Gas-chromatography
Física::Termodinàmica [Àrees temàtiques de la UPC]
Farmàcia--Investigació
Dosage form
Dichotomy method
chemistry.chemical_compound
Drug Stability
X-Ray Diffraction
Phase stability
Drug Discovery
Organic chemistry
Eutectic
Eutectic system
Phase diagram
Calorimetry
Differential Scanning
Chemistry
Temperature
Sorption
Ciències de la salut::Medicina::Farmacologia [Àrees temàtiques de la UPC]
Hygroscopic
Polymorphism (materials science)
Molecular Medicine
Thermodynamics
Thermal expansion
Crystallization
Flame photometric detection
Cysteamine
Calorimetry
State diagram
Powder
Crystals
Drugs -- Research
Cysteamine hydrochloride
Termodinàmica
Pressure
Polymorphism
Intermolecular interactions
Thermal-expansion tensor
Física::Electromagnetisme::Raigs X [Àrees temàtiques de la UPC]
Water
Humidity
Crystalline trimorphism
Enantiotropic phase relationship
Phase
Coordination
Physical chemistry
Powder diffraction
Zdroj: UPCommons. Portal del coneixement obert de la UPC
Universitat Politècnica de Catalunya (UPC)
Recercat. Dipósit de la Recerca de Catalunya
instname
ISSN: 1543-8392
Popis: 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.
Databáze: OpenAIRE
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