Pressure-temperature phase diagram of the dimorphism of the anti-inflammatory drug nimesulide
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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.
CitacióDel Barrio, M., Huguet, J., Robert, B., Rietveld, I., Céolin, R., Tamarit, J. L. Pressure-temperature phase diagram of the dimorphism of the anti-inflammatory drug nimesulide. "International journal of pharmaceutics", 15 Juny 2017, vol. 525, núm. 1, p. 54-59.
Versió de l'editorhttp://www.sciencedirect.com/science/article/pii/S0378517317302971