Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486439 | Journal of Pharmaceutical Sciences | 2011 | 12 Pages |
Abstract
Commercial and recrystallized polycrystalline samples of carprofen, a nonsteroidal anti-inflammatory drug, were studied by thermal, spectroscopic, and structural techniques. Our investigations demonstrated that recrystallized sample, stable at room temperature (RT), is a single polymorphic form of carprofen (polymorph I) that undergoes an isostructural polymorphic transformation by heating (polymorph II). Polymorph II remains then metastable at ambient conditions. Commercial sample is instead a mixture of polymorphs I and II. The thermodynamic relationships between the two polymorphs were determined through the construction of an energy/temperature diagram. The ab initio structural determination performed on synchrotron X-Ray powder diffraction patterns recorded at RT on both polymorphs allowed us to elucidate, for the first time, their crystal structure. Both crystallize in the monoclinic space group type P21/c, and the unit cell similarity index and the volumetric isostructurality index indicate that the temperature-induced polymorphic transformation IâII is isostructural. Polymorphs I and II are conformational polymorphs, sharing a very similar hydrogen bond network, but with different conformation of the propanoic skeleton, which produces two different packing. The small conformational change agrees with the low value of transition enthalpy obtained by differential scanning calorimetry measurements and the small internal energy computed with density functional methods.
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Authors
Giovanna Bruni, Fabia Gozzo, Doretta Capsoni, Marcella Bini, Piero Macchi, Petra Simoncic, Vittorio Berbenni, Chiara Milanese, Alessandro Girella, Stefania Ferrari, Amedeo Marini,