Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8994331 | Journal of Pharmaceutical Sciences | 2005 | 16 Pages |
Abstract
The thermodynamic relationships between the two known polymorphs of paracetamol have been investigated, and the subsequent pressureâtemperature and temperatureâvolume phase diagrams were constructed using data from crystallographic and calorimetric measurements as a function of the temperature. Irrespective of temperature, monoclinic Form I and orthorhombic Form II are stable phases at ordinary and high pressures, respectively. The I and II phase regions in the pressureâtemperature diagram are bordered by the IâII equilibrium curve, for which a negative slope (dp/dTââââ0.3 MPaâ·âKâ1) was determined although it was not observed experimentally. This curve goes through the IâIIâliquid triple point whose coordinates (pâââ234 MPa, Tâââ505 K) correspond to the crossing point of the melting curves, for which dp/dT values of +3.75 MPaâ·âKâ1 (I) and +3.14 MPaâ·âKâ1 (II) were calculated from enthalpy and volume changes upon fusion. More generally, this case exemplifies how the stability hierarchy of polymorphs may be inferred from the difference in their sublimation curves, as topologically positioned with respect to each other, using the phase rule and simple inferences resorting to Gibbs equilibrium thermodynamics. © 2004 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 94:524-539, 2005
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Authors
Philippe Espeau, René Céolin, JosepâLluis Tamarit, MarcâAntoine Perrin, JeanâPierre Gauchi, Franck Leveiller,