Accessing phase pure and stable acetaminophen polymorphs by thermal gradient approach.

Transcription

1 Supporting Information Accessing phase pure and stable acetaminophen polymorphs by thermal gradient approach. Basab Chattopadhyay +*, Luc Jacobs +, Piyush Panini +, Ingo Salzmann, Roland Resel # and Yves Geerts +*. + Laboratoire de Chimie des Polymères, CP 206/01, Faculté des Sciences, Université Libre de Bruxelles (ULB), Boulevard du Triomphe, 1050 Brussels, Belgium. Department of Physics, Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrook St. West, Montreal, Canada; Former address: Department of Physics, Humboldt Universität zu Berlin, Brook- Taylor-Straße 6, Berlin, Germany # Institute of Solid State Physics Graz University of Technology Petersgasse 16, 8010 Graz, Austria S1

2 Table of contents Experimental Table 1S: Summary of the cell parameters and space groups of the three PMpolymorphs. Figure 1S. Powder diffraction data of the as obtained sample of PM-Form I showing the indexation results and the corresponding Pawley fitting. Figure 2S. DSC plot for the as obtained PM-sample. The first cycle is shown in blue while the second cycle is shown in red. Transition temperatures are marked and the corresponding PM-forms are shown. Figure 3S. Powder diffraction data of PM- Form II as obtained by annealing the glassy PM phase (obtained on cooling the melt to RT) to 70 C. The cell parameters used and results of corresponding Pawley fitting are shown Figure 4S. In-plane GIXD data for PM-Form III obtained from the melt in absence of the thermal gradient. The data was collected in-house using Rigaku Ultima IV diffractometer. Comparison with the simulated powder diffraction pattern of Form III is shown. Figure 5S. Upper panel: Representation of the gradient parameters used in our experiments. Lower panel: POM images of the reference C8-BTBT-C8 showing the isotropic, liquid crystalline SmA phase and the crystalline phase. The value of x was determined from the length across which the SmA is present. Figure 6S. POM images PM-Form I obtained in the thermal gradient directly from the melt as the sample was translated from 180 C to 70 C with translation velocity varying in the range of 1 75 µm/s. Figure 7S. POM images PM-Form II obtained in the thermal gradient setup after seeding at 70 C. The sample was translated from 180 C to 70 C with translation velocity varying in the range of 1 75 µm/s. The appearance of cracks is most likely due to thermal contraction of the crystal as the samples are cooled down to room temperature. Figure 8S. (a) Crystal packing of PM form I viewed along b and a axes. (b) Crystal packing of PM form I viewed along c axis. Figure 9S. Equilibrium crystal morphology of (a) Form I and (b) Form II of PM as visualized with the Materials Studio software. White arrow indicate the direction perpendicular to the substrate and the direction of the thermal gradient. S3 S5 S5 S6 S6 S7 S7 S8 S8 S9 S9 S2

3 Experimental: Description of the Apparatus The setup, whose schematic representation is given in Figure 1, consists of a Linkam GS350 temperature gradient system heating stage composed of two independent heating devices separated by a distance of 2.5 mm where the thermal gradient is installed. One is set at a temperature T h above the melting temperature (hot side) and the other at a temperature T c below the crystallization temperature (cold side) of PM. Materials & Sample Preparation Acetaminophen (PM) was purchased from Sigma-Aldrich (BioXtra; purity grade 99%) and used without further purification. Each sample was prepared with 3.5 mg of PM deposited on a mm 3 precleaned thin glass substrate (Menzel Gläser cover glasses) and covered by the same glass substrate. All substrates were cleaned using a UV/ozone cleaner (BioForce Nanosciences, Inc., Ames, IA) for 20 min. The sample is initially placed entirely at the hot side and is slowly translated to the cold side at a constant speed (v) until all sample is at the cold side. A mm 3 microscope glass slide (Marienfeld Cat. No ) is intercalated between the heating stages and the sample to ensure a constant displacement velocity of the sample. The cover substrates were removed for X-ray diffraction analysis. This resulted in almost equal amounts of material on the two glass substrates (both usable for X-ray diffraction measurements). Identical sample preparation was employed for the reference material, C8- BTBT-C8. Determination of Gradient The exact value of the gradient conditions can be accurately determined using a reference material that exhibits an intermediate phase between the isotropic and the crystalline phase. In this respect C8-BTBT-C8 was found to be an ideal reference material with a liquid crystalline phase (SmA) with a characteristic type transition. 1 The temperatures of phase transitions were obtained from C8-BTBT-C8 film sandwiched between glass plates and cooled from the melt (at 5 C/min) without the thermal gradient. Under the current experimental conditions i.e T h = 180 C and T c =70 C, the value of x (the length across the sample where the SmA phase is present) was determined as 0.986(8) mm (averaged over 55 data points collected at different translation velocity). The variation of the gradient value and the effective cooling rate is listed in Figure 5S along with a POM image of C8-BTBT-C8 used to determine the value of x. It must be mentioned here that x changes depending on the values of T h and T c. Diffraction experiments Specular X-ray Diffraction (sxrd) measurements were performed on a Bruker D8 Advance/ Rigaku Ultima IV diffractometer at 293(2)K using Cu Kα radiation (λ = Å). The in-plane X-ray diffraction pattern was recorded using a Rigaku Ultima IV diffractometer under grazing incidence geometry by fixing the incident angle of the beam, α i at Diffraction patterns S3

4 were collected with an angular resolution of 0.02 per step and a typical counting time of 10 s per step, using the θ/θ reflection geometry. The X-ray diffraction patterns of the bulk powder were indexed using DICVOL06 program 2 incorporated in DASH software. 3 Pawley fitting 4 module of DASH was used to fit the experimental pattern with the known cell parameters of PM-Form I and II. Grazing incidence X-ray diffraction (GIXD) experiments were performed at the KMC-2 beamline at the BESSY II synchrotron radiation source (Helmholtz Zentrum Berlin (HZB), Berlin, Germany) 5 using an X-ray wavelength of 1.00 Å. A 2D VÅNTEC-2000 Mikrogap detector (BRUKER) equipped with an anti-air-scatter cone was used to record intensities. An incident angle of α i = 0.15, close to the critical angle of the substrate, was chosen to enhance the scattered intensities and suppress scattering from the substrate. Data processing was carried out using the software package PyGid. 6 Polarized Optical Microscopy (POM) The thermal gradient apparatus is mounted on a polarized optical microscope Nikon Eclipse 80i so that images can be taken before, during, and after the thermal gradient to obtain qualitative information on the crystallization behaviour. Crystal Morphology Calculations The crystal morphology of Form I and II of PM was modeled from the crystal structure obtained from Cambridge Structural Database (CSD) with code HXACAN30 and HXACAN08, respectively, using the Morphology module of the Materials Studio package. 7 References: (1) Grigoriadis, C.; Niebel, C.; Ruzié, C.; Geerts, Y. H.; Floudas, G. J. Phys. Chem. B 2014, 118 (5), (2) Boultif, A.; Louer, D. J. Appl. Crystallogr. 2004, 37 (5), (3) David, W. I. F.; Shankland, K.; van de Streek, J.; Pidcock, E.; Motherwell, W. D. S.; Cole, J. C. J. Appl. Crystallogr. 2006, 39 (6), (4) Pawley, G. S. J. Appl. Crystallogr. 1981, 14 (6), (5) Erko, A.; Packe, I.; Hellwig, C.; Fieber-Erdmann, M.; Pawlizki, O.; Veldkamp, M.; Gudat, W. In AIP Conference Proceedings; AIP, 2000; Vol. 521, pp (6) Moser, A. Crystal structure solution based on grazing incidence X-ray diffraction: software development and application to organic films, Graz University of Technology, Austria, (7) MS Modeling, Accelrys Software Inc.: San Diego, CA, S4

5 Table 1S: Summary of the cell parameters and space groups of the three PM-polymorphs. Form I II III Space group P2 1 /n Pbca Pca2 1 a[å] b[å] c [Å] β [ ] Cell parameters and spacegroup information of forms I and II were obtained from the Pawley fitting module of DASH. For Form III the corresponding data was obtained from Cambridge Structural Database (CSD) with code HXACAN29. Figure 1S. Powder diffraction data of the as obtained sample of PM showing the indexation results and the corresponding Pawley fitting. S5

6 Figure 2S. DSC plot for the as obtained PM-sample. The first cycle is shown in blue while the second cycle is shown in red. Transition temperatures are marked and the corresponding PM-forms are shown. Figure 3S. Powder diffraction data of PM- Form II as obtained by annealing the glassy PM phase (obtained on cooling the melt to RT) to 70 C. The cell parameters used and results of corresponding Pawley fitting are shown. S6

7 Figure 4S. In-plane GIXD data for PM-Form III obtained from the melt in absence of the thermal gradient. The data was collected in-house using Rigaku Ultima IV diffractometer. Comparison with the simulated powder diffraction pattern of Form III is shown. Figure 5S. Upper panel: Representation of the gradient parameters used in our experiments. Lower panel: POM images of the reference C8-BTBT-C8 showing the isotropic, liquid crystalline SmA phase and the crystalline phase. The value of x was determined from the length across which the SmA is present. S7

8 Figure 6S. POM images PM-Form I obtained in the thermal gradient directly from the melt as the sample was translated from 180 C to 70 C with translation velocity varying in the range of 1 75 µm/s. Figure 7S. POM images PM-Form II obtained in the thermal gradient setup after seeding at 70 C. The sample was translated from 180 C to 70 C with translation velocity varying in the range of 1 75 µm/s. The appearance of cracks is most likely due to thermal contraction of the crystal as the samples are cooled down to room temperature. S8

9 Figure 8S. (a) Crystal packing of PM form I viewed along b and a axes. (b) Crystal packing of PM form II viewed along c axis. Figure 9S. Equilibrium crystal morphology of (a) Form I and (b) Form II of PM as visualized with the Materials Studio software. White arrow indicate the direction perpendicular to the substrate and the thermal gradient. S9