Emeline Dudognon1, Florence Danède, Marc Descamps, Natália T Correia. 1. Laboratoire de Dynamique et Structure des Matériaux Moléculaires, UMR CNRS 8024, ERT 1066, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq Cedex, France. emeline.dudognon@univ-lille1.fr
Abstract
PURPOSE: The aim of this work is to search for the existence of crystalline polymorphism for racemic Ibuprofen. METHODS: The pharmaceutical material was studied by X-ray diffraction to identify crystalline phases, and by Differential Scanning Calorimetry to follow the thermodynamic evolution of these forms versus temperature. RESULTS: Results presented here show that, in addition to the already known conventional crystalline phase, whose nucleation domain extends between 233 K and 263 K and which melts at 349 K, racemic Ibuprofen can crystallize in another polymorphic phase. The nucleation of this new polymorphic variety is triggered by a stay at least 60 degrees below the glass transition temperature Tg of Ibuprofen (Tg = 228 K). This nucleation is probably of heterogeneous type. The new phase melts well below the conventional one, i.e. at 290 K. A schematic free energy diagram is provided allowing establishing the relative thermodynamic stability of the two polymorphs. CONCLUSIONS: These results establish, for the first time, that Ibuprofen can exist under two different crystalline phases which constitute a monotropic system, the new form being metastable.
PURPOSE: The aim of this work is to search for the existence of crystalline polymorphism for racemic Ibuprofen. METHODS: The pharmaceutical material was studied by X-ray diffraction to identify crystalline phases, and by Differential Scanning Calorimetry to follow the thermodynamic evolution of these forms versus temperature. RESULTS: Results presented here show that, in addition to the already known conventional crystalline phase, whose nucleation domain extends between 233 K and 263 K and which melts at 349 K, racemic Ibuprofen can crystallize in another polymorphic phase. The nucleation of this new polymorphic variety is triggered by a stay at least 60 degrees below the glass transition temperature Tg of Ibuprofen (Tg = 228 K). This nucleation is probably of heterogeneous type. The new phase melts well below the conventional one, i.e. at 290 K. A schematic free energy diagram is provided allowing establishing the relative thermodynamic stability of the two polymorphs. CONCLUSIONS: These results establish, for the first time, that Ibuprofen can exist under two different crystalline phases which constitute a monotropic system, the new form being metastable.
Authors: Michael W Stocker; Matthew J Harding; Valerio Todaro; Anne Marie Healy; Steven Ferguson Journal: Pharmaceutics Date: 2022-05-14 Impact factor: 6.525