Can the study of self-assembly in solution lead to a good model for the nucleation pathway? The case of tolfenamic acid.† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc00522a

Tolfenamic acid Form I (CAS no.13710195, >98% purity) was purchased from Sigma Aldrich and used without further purification. TA Form II was crystallised by crash cooling an ethyl acetate solution (3.45 g TA Form I and 50.00 g of ethyl acetate) to 283.15 K. Both forms were isolated as pure phases as judged by their powder X-ray diffraction (PXRD) patterns. Ethyl acetate (EtOAc), ethanol and 2-propanol were purchased from VWR International Ltd. (UK) and deuterated ethanol (EtOD) from Sigma Aldrich (>99.5%D). All solvents were of analytical reagent grade and the molar purities were > 99.5%. Powder X-ray diffraction (PXRD) was performed using a Rigaku miniflex X-ray powder diffractometer at a wavelength of 1.5406 Å controlled by DIFFRACPLUS software from 4° to 40° with a step size of 0.03°. The FTIR spectra of solutions of TA in EtOD were recorded in 0.50 or 1.00 mm thick liquid-sample cells, using a Perkin SpectrumTwo spectrometer with 2 cm-1 resolution. The spectra were corrected for the (small) solvent contribution by recording solvent spectra in the same liquid cell and subtracting these from the solution spectra. Differential Scanning Calorimetry (DSC) experiments were performed using either a Mettler Toledo DSC 30 instrument controlled by Mettler TC15 complete with a liquid nitrogen cooling system with data analyzed by STARe software v.610 or a TA DSC Q100 with software universal analysis 2000 v. 4.5A. A heating rate of 10 Kmin-1 was used.