Pressure-temperature phase diagram of the dimorphism of the anti-inflammatory drug nimesulide

Publication date: 15 June 2017 Source:International Journal of Pharmaceutics, Volume 525, Issue 1 Author(s): M. Barrio, J. Huguet, B. Robert, I.B. Rietveld, R. Céolin, J.Ll. Tamarit 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 T I-L =422.4±1.0K, ΔI→L H =117.5±5.2Jg−1, T II-L =419.8±1.0K and ΔII→L H =108.6±3.3Jg−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. Graphica...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research