Acetaminophen Research Today is a free monthly online journal that collates and summarizes the latest research about Acetaminophen, including details on paracetamol, pain relief, side effects, toxicity. | ||||||||
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Polymorphism of paracetamol: relative stabilities of the monoclinic and orthorhombic phases inferred from topological pressure-temperature and temperature-volume phase diagrams.Espeau P, Céolin R, Tamarit JL, Perrin MA, Gauchi JP, Leveiller F Laboratoire de chimie physique, Faculté de Pharmacie de I'Université Paris 5, 4 avenue de I'Observatoire, 75006 Paris, France. philippe.espeau@univ-paris5.fr The thermodynamic relationships between the two known polymorphs of paracetamol have been investigated, and the subsequent pressure-temperature and temperature-volume 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 pressure-temperature diagram are bordered by the I-II equilibrium curve, for which a negative slope (dp/dT approximately -0.3 MPa x K(-1)) was determined although it was not observed experimentally. This curve goes through the I-II-liquid triple point whose coordinates (p approximately 234 MPa, T approximately 505 K) correspond to the crossing point of the melting curves, for which dp/dT values of +3.75 MPa x K(-1) (I) and +3.14 MPa x K(-1) (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. Published 7 February 2005 in J Pharm Sci, 94(3): 524-39.
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