Thermal, spectroscopic, and ab initio structural characterization of carprofen polymorphs.
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.
CSGI Department of Physical Chemistry M Rolla, Pavia 27100, Italy. giovanna.bruni@unipv.it
Giovanna
G
Bruni
Fabia
F
Gozzo
Doretta
D
Capsoni
Marcella
M
Bini
Piero
P
Macchi
Petra
P
Simoncic
Vittorio
V
Berbenni
Chiara
C
Milanese
Alessandro
A
Girella
Stefania
S
Ferrari
Amedeo
A
Marini
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013816:Thermodynamics; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; C007005:carprofen