Pressure-temperature phase diagram of the dimorphism of the anti-inflammatory drug nimesulide
Understanding the phase behavior of active pharmaceutical ingredients is important for formulations of dosage forms and regulatory reasons. Nimesulide is an anti-inflammatory drug that is known to exhibit dimorphism; however up to now its stability behavior was not clear, as few thermodynamic data w...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/104659 |
| Acceso en línea: | https://hdl.handle.net/2117/104659 https://dx.doi.org/10.1016/j.ijpharm.2017.04.016 |
| Access Level: | acceso abierto |
| Palabra clave: | Calorimetry Crystallography Polymorphism (Crystallography) Thermodynamics Polymorphism Pressure-temperature phase diagram Phase behavior Preformulation Termodinàmica Cristal·lografia Calorimetria Polimorfisme (Cristal·lografia) Àrees temàtiques de la UPC::Física |
| Sumario: | Understanding the phase behavior of active pharmaceutical ingredients is important for formulations of dosage forms and regulatory reasons. Nimesulide is an anti-inflammatory drug that is known to exhibit dimorphism; however up to now its stability behavior was not clear, as few thermodynamic data were available. Therefore, calorimetric melting data have been obtained, which were found to be TI-L = 422.4 ± 1.0 K, ¿I ¿ LH = 117.5 ± 5.2 J g-1, TII-L = 419.8 ± 1.0 K and ¿II ¿ LH = 108.6 ± 3.3 J g-1. In addition, vapor-pressure data, high-pressure melting data, and specific volumes have been obtained. It is demonstrated that form II is intrinsically monotropic in relation to form I and the latter would thus be the best polymorph to use for drug formulations. This result has been obtained by experimental means, involving high-pressure measurements. Furthermore, it has been shown that with very limited experimental and statistical data, the same conclusion can be obtained, demonstrating that in first instance topological pressure-temperature phase diagrams can be obtained without necessarily measuring any high-pressure data. It provides a quick method to verify the phase behavior of the known phases of an active pharmaceutical ingredient under different pressure and temperature conditions. |
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