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Crystallization of Organic Glasses: How Does Liquid Flow Damage Surface Crystal Growth? Daniele Musumeci, Mariko Hasebe, and Lian Yu Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.6b00268 • Publication Date (Web): 11 Apr 2016 Downloaded from http://pubs.acs.org on April 12, 2016

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Crystal Growth & Design

Crystallization of Organic Glasses: How Does Liquid Flow Damage Surface Crystal Growth? Daniele Musumeci,ac Mariko Hasebe,a and Lian Yuab a

School of Pharmacy and b Department of Chemistry, University of Wisconsin – Madison, Wisconsin

53705, USA. c Current address: Department of Chemistry, York College of The City University of New York, Jamaica, NY 11451, USA ABSTRACT. Organic glasses can grow crystals much faster on the free surface than in the interior, a result of the high mobility of surface molecules. A puzzling property of this process is that it is active in the glassy state, but disrupted as the glass is heated above the glass transition temperature Tg to become a fluid, despite the large increase of mobility. To understand this phenomenon, high-resolution microscopy was used to observe surface crystal growth in amorphous indomethacin (IMC) in two polymorphs (α and γ). α IMC represents the general case of strong disruption of surface growth, while γ IMC represents the opposite situation where the effect is weak. We observed that heating above Tg causes liquid flow toward the crystals of both polymorphs. The essential difference between the polymorphs is that γ IMC grows as compact domains and its uniformly advancing growth front is unperturbed by the onset of liquid flow. In contrast, α IMC grows segregated needles and liquid flow strongly alters the crystal/liquid interface. This effect arises because the slow-growing flanks of needle crystals are wetted and embedded by the liquid. This explanation has support from independent observations that polystyrene spheres (a model for slow-growing crystals) are embedded on the timescale of crystal growth.

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INTRODUCTION Glasses are amorphous solids prepared by cooling liquids, condensing vapors, and evaporating solutions while preventing crystallization. Although familiar glasses are inorganic and polymeric, organic glasses of relatively low molecular weights are being explored for applications in drug delivery, bio-preservation, and organic electronics.1,2,3,4 In all these applications, amorphous materials must resist crystallization; otherwise, their advantages over crystals are lost. Recent studies have observed that surface molecules on organic glasses can be extremely mobile5,6,7 and this high mobility enables rapid crystal growth on a free surface.8,9,10,11,12,13,14 In this mode of crystal growth, crystals grow laterally and upward on the amorphous surface and are surrounded by depressed grooves or depletion zones.15 Fast surface crystal growth has also been reported for amorphous Se16 and Si17 and for a metallic glass,18 while reports differ on the existence of the phenomenon in silicate glasses.19,20,21,22 A puzzling feature of surface crystal growth on organic glasses is that the process is active in the glassy state, but disrupted as the glass is heated above the glass transition temperature Tg to become a fluid.14 This effect is shown in Figure 1 for two polymorphs of indomethacin (IMC). Below Tg, the growth rate of surface crystals us increases steadily with rising temperature, but this increase is halted or slowed near Tg. This effect is counterintuitive since the crystal growth process slows down with an increase of molecular mobility. Also noteworthy is the different

Figure 1. Velocity of crystal growth in amorphous indomethacin (IMC) in the bulk (ub) and at the free surface (us) for (a) α IMC and (b) γ IMC. GC refers to the glass-to-crystal growth mode in the bulk. Reproduced from Ref. 14.


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responses of the two IMC polymorphs: the surface growth of α IMC is strongly perturbed by fluidity, while the effect is much weaker for γ IMC. Hasebe et al. propose that the disruption effect arises because a flowing liquid wets and embeds surface crystals, frustrating their upward growth that characterizes the steady state of crystallization.14 For all the systems studied to date, this effect is observed near the calorimetric Tg, at which viscosity is approximately 1010 Pa s and drops very rapidly with heating (by about one order of magnitude every 4 K). The increasing fluidity presumably allows the liquid to flow on the timescale of crystal growth. Hasebe et al. further speculate that the different morphologies of α and γ IMC – needles and compact domains, respectively, cause them to be perturbed differently by a flowing liquid. To further test this hypothesis, we used scanning electron microscopy (SEM) and atomic force microscopy (AFM) to examine the growth of surface crystals on amorphous IMC at different temperatures. We find that heating above Tg indeed activates liquid flow toward crystals. The essential difference between the two polymorphs is that the compact domains of γ IMC advance rapidly in all directions and can withstand the perturbation by liquid flow, whereas the segregated needles of α IMC have slow-growing flanks, allowing the liquid to strongly alter the crystal/liquid interface. In active growth below Tg, needle-like crystals rise above the amorphous surface as they grow laterally, and are surrounded by surface grooves or depletion zones; in the disrupted state above Tg, the depletion zones disappear and the crystals are partially embedded. These results support the notion that fluidity disrupts the growth of surface crystals through the wetting and embedding of slow-growing faces. This explanation has additional support from the observation that polystyrene spheres, which serve as a model for slow-growing crystals, are embedded on the timescale of crystal growth. Our results argue that surface crystal growth on molecular glasses is enabled by surface diffusion and disrupted by viscous flow through the wetting and embedding of crystals.



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MATERIALS AND METHODS Indomethacin (1-(p-cholorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid, 99+%, γ polymorph), was purchased from Sigma-Aldrich and used as received. To prepare a sample for SEM and AFM, the crystalline substance was melted on a clean square coverslip at 15 K above the melting point and covered with a smaller round coverslip (typically 15 mm in diameter). The assembly was cooled to below Tg by contact with a metal block at room temperature. The sample was confirmed to be free of crystals by polarized light microscopy. The square coverslip was detached by bending its edges away from the sample, yielding an IMC film that adhered to the round coverslip on one side and was exposed on the other. The films were 10 – 100 µm thick. Surface crystallization was initiated by seeding on the free surface with α or γ IMC and incubating at 313 K (Tg – 2 K) for two days. Surface crystals were then allowed to grow at a chosen temperature. IMC polymorphs were identified by x-ray powder diffraction (Bruker D8 Advance diffractometer with Cu Ka radiation) and Raman microscopy (Thermo DXR). SEM was performed with a field-emission LEO 1530 low-voltage and high-resolution instrument operated at 6 KV and 12-14 mm working distance using an in-lens secondary electron detector. Before analysis, the sample was coated with a gold film of 10 nm thick (Denton Vacuum Desk II; 50 mTorr pressure, 45 mA current and 30 s deposition). The gold coating halted surface crystal growth and prevented charging during SEM analysis. To further prevent charging, the coated sample was attached to a metal stub with a carbon tape. Some samples were examined in cross sections to determine the extent of bulk crystal growth. To prepare a sample for this purpose, the round coverslip was pre-scratched along the diameter and just before SEM analysis, snapped in half along the scratch to expose a cross section of the IMC film. Real-time AFM was performed with a Veeco Multimode IV Scanning Probe Microscope in the tapping mode under N2 purge. An AFM hostage was used for temperature control and calibrated against the melting point of o-terphenyl (329 K).


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To deposit polystyrene (PS) particles on an IMC glass film, a suspension of microspheres of 500 nm diameter (Polysciences Inc.) was centrifuged for 3 minutes at 13200 RPM (Eppendorf 5415D). The supernatant was pipetted out and the spheres were re-suspended in deionized water. The aqueous suspension was spin-coated on an IMC glass film at 1000 RPM for 2-3 minutes (Laurell spin coater WS400-6NPP-LITE) and the sample was dried in vacuum overnight. The sinking of PS particles into amorphous IMC was measured by AFM at constant temperature in dry N2.

RESULTS AND DISCUSSION

IMC can grow in two polymorphs (α and γ)23,24,25 on the surface of an IMC glass. These polymorphs have different morphologies (Figure 1), with α IMC growing as needles and γ as compact domains, and they respond differently to heating above Tg. Below we describe the surface growth of each polymorph characterized by highresolution microscopy both in the active growth state (below Tg) and in the disrupted growth state (above Tg).

γ IMC. Figure 2 shows the SEM images of γ IMC

surface

crystals

grown

at

different

temperatures: 313 K (Tg – 2 K), 325 K (Tg + 10 Figure 2. SEM images of the surface crystals of γ IMC K), and 333 K (Tg +18 K). In this temperature

grown at 313 K, 325 K, and 333 K. The samples were examined in cross sections, showing both lateral growth and penetration into the bulk. us is the velocity of surface crystal growth. ub is the velocity of bulk crystal growth.



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range, the solid glass transforms to a flowing liquid. From 313 K to 325 K, the crystalline region has the same average height as the amorphous surface region; there is no significant change in the crystal morphology or its relation to the amorphous phase (Figure 2). This is consistent with the relatively weak effect of heating above Tg on the growth kinetics of γ IMC surface crystals (Figure 1). At 333 K, the crystalline domain behind the growth front is significantly below the amorphous surface (Figure 2). Close examination shows significant curving up of the amorphous surface near the crystals, a feature confirmed by AFM (see later), consistent with liquid flowing toward the crystals. Despite this evidence of liquid flow, however, the surface growth of γ IMC remains active at this temperature. Figure 3 shows real-time AFM images of γ IMC surface crystals growing at 317 K (Tg + 2 K) and 329 K (Tg + 14 K). At both temperatures, the crystal growth front advances steadily into the amorphous region. The growth velocities from these AFM measurements agree with those from LM measurements (Figure 4).14 Note that the crystalline

Figure 3. Real-time AFM images of γ IMC crystals growing on the surface of amorphous IMC at 313 K and 329 K. Color scale = 300 nm

Figure 4. Lateral velocity of surface crystal growth on amorphous IMC (us). Solid circles are from Ref. (14) measured by light microscopy and open triangles are from this work measured by AFM.


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domains formed at these temperatures have similar textures and the surrounding amorphous surface is flat within the region of analysis, indicating undisrupted growth even well above Tg.

α IMC. Figure 5 shows the SEM images of α IMC surface crystals grown at different temperatures. In contrast to γ IMC, α IMC grows as segregated needles. In active growth (303 K or Tg – 12 K), the needles rise above the glass surface while spreading laterally and are surrounded by depletion zones; the tip of the needle is raised above the amorphous surface (Figure 5). At 323 K (Tg + 8 K), surface crystals have very different morphologies: they are not as high above the amorphous surface as they are during active growth at 303 K; they appear to partially sink into the liquid; the tip of the needle now touches the liquid (Figure 5). Meanwhile, the depletion zones flanking the needle-like crystal in active growth are no longer visible. Curiously, there are holes at the crystal/liquid boundary, which could be the remnant of the depletion zones after being filled by the incoming liquid. At 333 K, crystal sinking into the liquid is more evident (Figure 5). Together these results show that heating above Tg activates liquid flow and strongly alters the crystal/amorphous interface for this polymorph. Figure 6 shows real-time AFM images of α IMC surface crystals growing at different temperatures. Consistent with the SEM results, the surface crystals in active growth at 317 K are high above the amorphous surface, but at 323 K, Figure 5. SEM images to show the effect of

they do not rise as high and become wider. During real- heating on the growth of α IMC surface crystals at 303 K, 323 K and 333 K.



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time observations, many needles show little growth, and only a few show obvious growth (see the arrows in the 323 K images for an example); eventually the fastgrowing fibers slow down as well. Shown in Figure 4a are the growth velocities of the active-growing crystals measured by AFM, not the dormant ones. These results agree with those measured previously by optical microscopy.14 At 329 K, the liquid surface is clearly uneven, curving up toward the crystals. The bright spots at the tips of the crystals are regions of elevated liquid Figure 6. Real-time AFM images of α IMC levels. This feature is in sharp contrast to the relatively

growing on the amorphous surface at 317 K, 323 K, and 329 K. Color scale = 1500 nm. Arrows show the fast growing fibers.

flat amorphous surface surrounding γ IMC crystals and an indicator of liquid flow.

Embedding of PS particles. To test the possibility that slow-growing crystals can be embedded at the onset of liquid flow, PS microspheres (500 nm diameter) were deposited on the surface of IMC and their height was measured by AFM as a function of time. PS was selected because it has similar surface tension as IMC and can serve as a model for slow-growing IMC crystals. Our results show that PS spheres can indeed sink into amorphous IMC above Tg. For example, Figure 7a shows the process of embedding at 327 K observed by AFM. Figure 7b shows the height of the sphere as a function of time. The initial height is approximately 500 nm, the diameter of the PS spheres, and the height decreases over time.


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Figure 7c shows that the embedding process is reasonably well described as a process driven by surface tension and resisted by viscous drag. A velocity of embedding uembed was calculated for a sphere half embedded and half exposed (the slope of the red line in Figure 7b); the results are shown in Figure 7c. (As Figure 7b shows, uembed is also roughly the average embedding rate for the first 80 % of the embedding process.)

According

to

Daley

et

al.,26

uembed

is

approximately given by the characteristic rate of viscous relaxation F, defined as F = γ/2η, where γ is surface tension, and η is viscosity. For IMC, F has been measured from the viscous relaxation of surface gratings,5 and the results are displayed as solid circles in Figure 7c. The values of F at lower temperatures are further extrapolated assuming viscosity is proportional to the structural relaxation time.27,28 Notice the reasonable agreement between F and uembed of PS particles, which argues that viscous relaxation is the mechanism for the embedding of PS particles.

Figure 7. Real-time AFM images (a) and height vs. time plot of 500 nm PS spheres embedding into liquid IMC at 327 K (b). (c) The sinking velocities of PS particles (open symbols) overlain with the values of F measured from the decay of surface grating (solid symbols)

Surface Vs Glass-to-Crystal growth. In view of the finding of this work, it is of interest to compare the surface crystal growth on organic glasses to the so-called glass-to-crystal (GC) growth, especially their similar response to the onset of fluidity. GC growth is another surprisingly fast mode of crystal growth mode; it differs from the surface mode studied here in that it occurs in the bulk of molecular



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glasses.29,30,31,32 This growth mode causes crystal growth rate to vastly exceed the prediction of standard models,33,34,35 in which bulk diffusion is assumed to limit the rate of crystal growth. GC growth is currently known for 12 systems,36 and received several different explanations.30,31,32,37,38,39 A striking similarity between GC growth and surface crystal growth studied here is that both can be disrupted as glasses are heated above Tg to gain fluidity.14,30 Musumeci et al. reported that for GC growth to exist, the growth rate must exceed a threshold set by the level of fluidity: D/u < 7 pm; that is, for a GC growth process of linear velocity u, the diffusivity of the liquid must not exceed Dmax = (7 pm) u;36 the higher the GC growth velocity, the higher the Dmax. This study finds a qualitatively similar condition for the existence of surface crystal growth: in the case of γ IMC, the growth front advances so rapidly that the onset of fluidity has a minor effect on the process, but in the case of α IMC, the flanks of needle-like crystals grow slowly, allowing the flowing liquid to wet and embed the crystals and disrupt their growth. These similar responses of the two glassy-state crystal growth modes are consistent with the notion that surface mobility supports both processes. In surface crystal growth, the amorphous surface surrounding the crystals can rapidly supply molecules to them, at a rate much faster than bulk diffusion. In the bulk GC growth, it is speculated that voids and free surface are continuously created as the growth front advances, again allowing surface mobility to supply molecules to the crystals.39 In the case of γ IMC, both surface growth and bulk GC growth have been observed (Figure 1). Comparing their kinetics, we find that the surface process is perturbed to a lesser extent than the bulk process; that is, it is able to persist up to a higher temperature. Hasebe et al. have made similar observations for other molecular glasses – OTP and NIF, noting that GC growth is terminated more abruptly by fluidity than surface growth. The different responses of the two growth modes to the onset of liquid flow might be a result of their different growth environments. At the free surface, the high mobility of surface molecules supports the fast crystal growth, and the crystals can grow upward into


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free space. At the onset of liquid flow, the upward growth might allow the crystals to avoid the oncoming liquid and maintain the same growth mechanism that relies on surface mobility. In bulk crystal growth, however, the crystals are surrounded by the liquid and the activation of liquid flow could more effectively disturb the GC growth mode, causing a more abrupt termination.

CONCLUSION Organic glasses can grow crystals much faster on the free surface than in the interior, a result of their high surface mobility. A puzzling property of this process is that it is disrupted if the glass is heated above Tg to become a flowing liquid, with the disruption being stronger for the growth of segregated needles (α IMC) than the growth of compact domains (γ IMC). This phenomenon is counterintuitive since crystal growth slows down as molecular mobility increases. We find that the key factor controlling this phenomenon is whether liquid flow is fast on the timescale of crystal growth. For γ IMC, whose compact growth front advances rapidly and uniformly, its growth is only weakly perturbed. In contrast, the slow-growing flanks of α IMC allow significant liquid flow on the timescale of crystal growth, causing the wetting and embedding of the crystals and the termination of the growth mode. The viscous embedding of PS spheres demonstrates that a flowing liquid can indeed embed slow-growing crystals, thereby damaging the process of surface crystal growth. Previous studies have shown that surface diffusion supports the growth of surface crystals on molecular glasses.7 This work finds that upon heating above Tg, liquid flow is activated toward surface crystals and can damage their growth process. Together, these results are consistent with the notion that increasing temperature causes a change in the mechanism by which molecules come to the crystals, from surface diffusion at low temperatures to viscous flow at high temperatures. This change occurs because for a given temperature increase, viscous flow speeds up more rapidly than surface diffusion, eventually



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allowing viscous flow to dominate mass transport. The same change is observed in the decay of surface gratings on molecular glasses without crystallization: at a given wavelength, low-temperature decay occurs by surface diffusion, while high-temperature decay by viscous flow.5,6,7 This change of mechanism is ultimately responsible for the counterintuitive response of surface crystallization on molecular glasses to the onset of fluidity. A flowing liquid allows fast mass transport, but it wets and embeds surface crystals, disrupting their growth.

ACKNOWLEDGMENTS. We thank the NSF (DMR-1206724) for supporting this work.

REFERENCES

1 Shirota, Y. Photo- and electroactive amorphous molecular materials-molecular design, syntheses, reactions, properties, and applications. J. Mater. Chem. 2005, 15, 75-93. 2 Forrest, S. R.; Thompson, M. E. Introduction: Organic Electronics and Optoelectronics. Chem. Rev. 2007, 107, 923-925. 3 Yu, L. Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv. Drug Delivery Rev. 2001, 48, 27-42. 4 Crowe, J. H.; Carpentier, J. F.; Crowe, L. M. The role of vitrification in anhydrobiosis. Annu. Rev. Physiol. 1998, 60, 73-103. 5 Zhu, L.; Brian, C.; Swallen, S. F.; Straus, P. T.; Ediger, M. D.; Yu, L. Surface Diffusion of an Organic Glass. Phys. Rev. Lett. 2011, 106, 256103


Page 13 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


6 Brian, C. B.; Yu, L. Surface Self-Diffusion of Organic Glasses. J. Phys. Chem. A 2013, 117, 13303−13309. 7 Zhang, W.; Brian, C. W.; Yu, L. Fast Surface Diffusion of Amorphous o-Terphenyl and its Competition with Viscous Flow in Surface Evolution. J. Phys. Chem. B. 2015, 119, 5071–5078. 8 Wu, T.; Yu, L. Surface crystallization of indomethacin below glass transition temperature. Pharm. Res. 2006, 23, 2350-2355. 9 Sun, Y.; Zhu, L. Kearns, K. L.; Ediger, M. D.; Yu, L. Glasses crystallize rapidly at free surfaces by growing crystals upward. Proc. Natl. Acad. Sci., 2011, 108, 5990-5995. 10 Zhu, L.; Wong, L.; Yu, L. Surface-enhanced crystallization of amorphous nifedipine. Mol. Pharmaceutics, 2008, 5, 921-926. 11 Zhu, L. Jona, J.; Nagapudi, K.; Wu, T. Fast surface crystallization of amorphous griseofulvin below Tg. Pharm. Res. 2010, 27, 1558-1567. 12 Wu, T.; Sun, Y.; Li, N.; de Villiers, M. M.; Yu, L. Inhibiting surface crystallization of amorphous indomethacin by nanocoating. Langmuir 2007, 23, 5148-5153. 13 Gunn, E.; Guzei, I. A.; Yu, L. Does Crystal Density Control Fast Surface Crystal Growth in Glasses? A Study with Polymorphs. Crystal Growth & Design 2011, 11, 3979-3984. 14 Hasebe, M.; Musumeci, D.; Powell, C,T.; Cai, T.; Gunn, E.; Zhu, L.; Yu, L. Fast Surface Crystal Growth on Molecular Glasses and Its Termination by the Onset of Fluidity. J. Phys. Chem. B 2014, 118, 7638−7646.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 17

15 Hasebe, M.; Musumeci, D.; Yu, L. Fast Surface Crystallization of Molecular Glasses: Creation of Depletion Zones by Surface Diffusion and Crystallization Flux. J. Phys. Chem. B 2015, 119, 3304-3311. 16 Stephens, R. B. Stress-Enhanced Crystallization in Amorphous Selenium Films. J. Appl. Phys. 1980, 51, 6197-6201. 17 Sallese, J. M.; Ils, A.; Bouvet, D.; Fazan, P.; Merritt, C. Modeling of the Depletion of the Amorphous-Silicon Surface during Hemispherical Grained Silicon Formation. J. Appl. Phys. 2000, 88, 5751-5755. 18 Cao, C. R.; Lu, Y. M.; Bai, H. Y.; Wang, W. H. High surface mobility and fast surface enhanced crystallization of metallic glass. Appl. Phys. Lett. 2015, 107, 141606. 19 Wittman, E.; Zanotto, E. D. Surface Nucleation and Growth in Anorthite Glass. J. Non-Cryst. Solids 2000, 271, 94-99. 20 Fokin, V. M.; Zanotto, E. D. Surface and Volume Nucleation and Growth in TiO2-Cordierite Glasses. J. Non-Cryst. Solids 1999, 246, 115-127. 21 Yuritsyn, N. S. Crystal growth on the surface and in the bulk of Na2O⋅2CaO⋅3SiO2-glass. In Nucleation Theory and Applications, Editors: J.W.R.Schmelzer, G.Roepke, V.B.Priezzhev. Dubna, JINR, 2005, p.22-42.

22 Wisniewski, W.; Bocker,C.; Kouli M.; Nagel M.; Rüssel, C. Surface Crystallization of Fresnoite from a Glass Studied by Hot Stage Scanning Electron Microscopy and Electron Backscatter Diffraction. Cryst. Growth Des. 2013, 13, 3794–3800. 23 Chen, X.; Morris, K. R.; Griesser, U. J.; Byrn, S. R.; Stowell, J. G. Reactivity differences of indomethacin solid forms with ammonia gas. J. Am. Chem. Soc. 2002, 124, 15012-15019.


Page 15 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


24 Galdecki, Z.; Glowka, M. L. Rockz Chem. 1976, 50, 1139-1148. 25 Cox, P. J.; Manson, P. L. 2003, Acta Crystallog. Sect. E. 2003, 59, 0986. 26 Daley, C. R.; Fakhraai, M. D.; Ediger, M. D.; Forrest, J. A. Comparing Surface and Bulk Flow of a Molecular Glass Former. Soft Matter 2012, 8, 2206-2212. 27 Wojnarowska, Z.; Adrjanowicz, K.; Wlodarczyk, P.; Kaminska, E.; Kaminski, K.; Grzybowska, K; Wrzalik, R.; Paluch, M.; Ngai, K. L. Broadband Dielectric Relaxation Study at Ambient and Elevated Pressure of Molecular Dynamics of Pharmaceutical: Indomethacin. J. Phys. Chem. B 2009, 113, 1253612545. 28 Goresy, T. E.; Böhmer, R. Dielectric Relaxation Processes in Solid and Supercooled Liquid Solutions of Acetaminophen and Nifedipine. J. Phys.: Condens. Matter 2007, 19, 205134. 29 Greet, R. J.; Turnbull, D. Glass Transition in o-Terphenyl. J. Chem. Phys. 1967, 46, 1243-1251. 30 Hikima, T. Adachi, Y.; Hanaya, M.; Oguni, M. Determination of Potentially HomogeneousNucleation-Based Crystallization in o-Terphenyl and an Interpretation of the Nucleation-Enhancement Mechanism. Phys. Rev. B 1995, 52, 3900-3908. 31 Konishi, T.; Tanaka, H. Possible Origin of Enhanced Crystal Growth in a Glass. Phys. Rev. B 2007, 76, 220201/ 1-220201/4. 32 Sun, Y.; Xi, H.; Chen, S.; Ediger, M. D.; Yu. L. Crystallization near Glass Transition: Transition from Diffusion-Controlled to Diffusionless Crystal Growth Studied with Seven Polymorphs. J. Phys. Chem. B 2008, 112, 5594-5601.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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33 Wilson, H. A. On the Velocity of Solidification and Viscosity of Suprecooled Liquids. Philos. Mag. 1900, 50, 238-251. 34 Turnbull, D. On the Relation between Crystallization Rate and Liquid Structure. J. Phys. Chem. 1962, 24, 609-613. 35 Ediger, M. D.; Harrowell, P.; Yu, L. Crystal Growth Kinetics Exhibit a Fragility-Dependent Decoupling from Viscosity. J. Chem Phys. 2008, 128, 034709/1-034709/6. 36 Musumeci, D.; Powell, C. T.; Ediger, M. D.; Yu, L. Termination of Solid State Growth in Molecular Glasses by Fluidity. J. Phys. Chem. Lett. 2014, 5, 1705-1710. 37 Stevenson, J. D.; Wolynes, P. G. The Ultimate Fate of Supercooled Liquids. J. Phys. Chem. A 2011, 115, 3713-3719. 38 Caroli, C.; Lemaître, A. Ultrafast Spherulitic Crystal Growth as a Stress-Induced Phenomenon Specific of Fragile Glass-Formers. J. Chem. Phys. 2012, 137, 114506/1-114506/9. 39 Powell, C. T.; Xi, H.; Sun, Y.; Gunn, E.; Chen, Y.; Ediger, M. D.; Yu, L. Fast Crystal Growth in oTerphenyl Glasses: A Possible Role for Fracture and Surface Mobility. J. Phys. Chem. B 2015, 119, 10124−10130.


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For Table of Contents Use Only

Crystallization of Organic Glasses: How Does Liquid Flow Damage Surface Crystal Growth? Daniele Musumeci,ac Mariko Hasebe,a and Lian Yuab a

School of Pharmacy and b Department of Chemistry, University of Wisconsin – Madison, Wisconsin

53705, USA. c Current address: Department of Chemistry, York College of The City University of New York, Jamaica, NY 11451, USA

In active growth, α indomethacin surface crystals rise above the amorphous surface while extending laterally and are surrounded by depletion zones; in the disrupted state above Tg, the depletion zones vanish and the crystals are embedded by liquid flow.


Crystallization of Organic Glasses: How Does ... - ACS Publications

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