logotype

Thermal, Spectroscopic, and Ab Initio Structural Characterization of Carprofen Polymorphs

Research Area: Uncategorized Year: 2011
Type of Publication: Article
Authors:
Journal: JOURNAL OF PHARMACEUTICAL SCIENCES Volume: 100
Number: 6 Pages: 2321-2332
Month: June
ISSN: 0022-3549
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 P2(1)/c, and the unit cell similarity index and the volumetric isostructurality index indicate that the temperature-induced polymorphic transformation I. II 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. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2321-2332, 2011
[ Back ]
Copyright © CSGI 2012 - Credits - Cookie Policy - Privacy - Consorzio per lo Sviluppo dei Sistemi a Grande Interfase, via della Lastruccia 3, 50019, Sesto Fiorentino, Italy