DYNAMICS OF AN ANHYDROUS SOLID FORM OF Na-IBUPROFEN FROM 1H AND 13C NUCLEAR RELAXATION TIMES

Ibuprofen is a very widely used non-steroidal analgesic and anti-inflammatory drug, delivered in many different solid formulations. The sodium salt of Ibuprofen has received considerable attention in pharmaceutical research and industry because, thanks to its higher water solubility, it acts more rapidly than the more common acid form of Ibuprofen. The stable form of Na-Ibuprofen at room temperature is a di-hydrated crystal, which has been widely studied and characterized.[1-2]. The di-hydrated form undergoes dehydration when heated above 80°C or exposed to P2O5 or to N2 atmosphere, giving rise to an anhydrous form named form 1 [3]. The structural properties of this form at room temperature have been investigated by X-Ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC) and Solid State NMR (SSNMR) [4]. In this work we have investigated form 1 by SSNMR in the temperature range 20-80°C. We have found that form 1 is not stable upon heating and it transforms into a new phase, form 2, which on the contrary results to be stable after further cooling and heating steps. This prompted us to investigate the molecular dynamic properties of Na-Ibuprofen in form 2, also with the aim of comparing them with those of form 1 and of the di-hydrated form. All the internal molecular motions with frequencies ranging from Hz to MHz regimes have been characterized in detail by combining 1H Fast Field Cycling (FFC) with the measurement of 13C and 1H spin-lattice relaxation times in the laboratory (T1) and rotating frames (T1?) carried out at a 1H Larmor frequency of 400 MHz and in the temperature range 20-80°C. The relaxation data have been simultaneously analysed with suitable models, determining motional parameters, such as activation energies and correlation times, which have shown interesting differences with form 1 and di-hydrated form. Acknowledgments This work was supported by the CA15209 COST Action (EURELAX). References [1] Y. Zhang and D. J. W. Grant, Acta Crystallogr. C, 2005, 61, m435-438. [2] E. Carignani, S. Borsacchi, and M. Geppi, J. Phys. Chem. A, 2011, 115, 8783-8790. [3] G. G. Z. Zhang, S. Y. L. Paspal, R. Suryanarayanan, and D. J. W. Grant, J. Pharm. Sci. 2003, 90, 1356-1366. [4] P. Rossi, E. Macedi, P. Paoli, L. Bernazzani, E. Carignani, S. Borsacchi, and M. Geppi, Cryst. Growth Des. 2014, 14, 2441-2452.