Non-Needle-like Morphology of Î²-Glycine Particles Formed from

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Non-Needlelike Morphology of #-Glycine Particles Formed from Water Solutions via Monodisperse Droplet Evaporation David I Trauffer, Anna K Maassel, and Ryan C. Snyder Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.5b01445 • Publication Date (Web): 03 Mar 2016 Downloaded from http://pubs.acs.org on March 6, 2016

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Crystal Growth & Design

Non-Needlelike Morphology of β-Glycine Particles Formed from Water Solutions via Monodisperse Droplet Evaporation David I. Trauffer, Anna K. Maassel and Ryan C. Snyder* Department of Chemical Engineering, Bucknell University, Lewisburg, Pennsylvania 17837, USA Phone: 570-577-2346 E-mail: [email protected] ABSTRACT The morphology and polymorphism are presented for crystalline glycine particles formed via monodisperse droplet evaporation. The resulting glycine particles are monodisperse with characteristic sizes of ~10 microns. The crystalline particles are found to exclusively consist of the metastable β polymorph regardless of being formed from water-ethanol solutions, wateracetone solutions or even pure water solutions. While the formation of β-glycine is expected in some solvent mixtures based on previous work, this work represents a unique environment to obtain β-glycine: from pure water solutions, where the solution droplets only interface with air, at the micron scale. Looking at morphology, the resulting particles are solid and not hollow, which is characteristically different from many other small molecular organic particles formed via monodisperse droplet evaporation. Further, the morphology within the particles shows varying degrees of plate-like crystal morphology and an absence of the typical needle-like habit of β-glycine usually found through other techniques. The presented polymorphism and morphology provide insights into the respective nucleation and growth mechanisms of β-glycine and further demonstrate the use of monodisperse droplet evaporation as a potential tool to enhance the study of particle engineering and investigate the formation of metastable polymorphs.

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Non-Needlelike Morphology of β-Glycine Particles Formed from Water Solutions via Monodisperse Droplet Evaporation David I. Trauffer, Anna K. Maassel and Ryan C. Snyder* Department of Chemical Engineering, Bucknell University, Lewisburg, Pennsylvania 17837, USA

Email: [email protected]


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ABSTRACT The morphology and polymorphism are presented for crystalline glycine particles formed via monodisperse droplet evaporation.

The resulting glycine particles are monodisperse with

characteristic sizes of ~10 microns. The crystalline particles are found to exclusively consist of the metastable β polymorph regardless of being formed from water-ethanol solutions, wateracetone solutions or even pure water solutions. While the formation of β-glycine is expected in some solvent mixtures based on previous work, this work represents a unique environment to obtain β-glycine: from pure water solutions, where the solution droplets only interface with air, at the micron scale. Looking at morphology, the resulting particles are solid and not hollow, which is characteristically different from many other small molecular organic particles formed via monodisperse droplet evaporation.

Further, the morphology within the particles shows

varying degrees of plate-like crystal morphology and an absence of the typical needle-like habit of β-glycine usually found through other techniques.

The presented polymorphism and

morphology provide insights into the respective nucleation and growth mechanisms of β-glycine and further demonstrate the use of monodisperse droplet evaporation as a potential tool to enhance the study of particle engineering and investigate the formation of metastable polymorphs.


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Introduction When designing a process for organic molecular crystalline products, both polymorphism and morphology (in this work referring to both the external particle morphology or habit as well as the internal morphology or the shape of the particle away from the surface) are critical in the resulting product properties.1 Polymorphism and morphology of organic molecular systems impact industries including pharmaceuticals, food products and specialty chemicals.2-5 In crystallization, the resulting morphology and polymorphism are dependent on both the chemical environment and the process by which crystals are formed. Many methods exist for controlling polymorphism and morphology including changing the solvent,6 adding other chemical agents,7 crystallizing from the melt or sublimate,8 and forming crystals under polarized light.9 In this work, we demonstrate the effect of using a unique process, growth via monodisperse droplet evaporation, along with the associated solvent choice on the polymorphism and morphology of glycine. Glycine is the simplest amino acid and provides a diversity of both crystal forms and crystal morphologies. Glycine is known to crystallize in at least five different polymorphs, three of which can be formed at atmospheric conditions: alpha (α), beta (β), and gamma (γ). At atmospheric conditions, γ-glycine is the most stable. While α-glycine is the most common and can be obtained through a cooling crystallization of a glycine-water solution, β-glycine typically requires more care to isolate. It has been grown from water-ethanol and water-methanol mixtures, but glycine is almost completely insoluble in alcohols, leading to very low yields.10,11 Sublimation of α or γ-glycine can lead to the β form crystallizing, but requires multiple additives in the sublimate.12 Freeze-drying a glycine solution in water has also led to forming β-glycine with an extremely slow temperature ramp, and β-glycine can also be formed in a glycine-ice eutectic mixture.13,14 Other nucleic acids have also been used successfully as additives to force


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the selective crystallization of β-polymorph.15 Other methods of obtaining β-glycine include rapidly mixing an aqueous solution of glycine and acetic acid with acetone,16 spray drying with a supercritical solution of carbon dioxide and ethanol at a pressure of 100 bar,17 crystallization from macromolecular emulsions,18,19 crystallization on bifunctional patterned surfaces20 and crystallization in nanoscale chambers.21, 22 Finally, growth on self-assembled monolayers,23 and growth on Pt Substrates have been used to obtain a mixture of α and β-glycine.24 Spray drying from water solutions has previously shown both mixtures of α and β-glycine25 as well as only αglycine26, depending on the conditions.

Glycine’s polymorphs also present a diversity of

morphologies. While the γ and α polymorphs often present block-like morphologies, with bipyramidal and coffin shapes respectively27, the β polymorph typically presents a needle-like habit28. In this work, we investigate the use of monodisperse droplet generation and evaporation, specifically the use of a vibrating orifice aerosol generator (VOAG), to produce crystalline glycine particles.

We will demonstrate unique conditions to form β-glycine and unique

morphologies of β-glycine. The demonstrated polymorphism and morphologies impact theories regarding the nucleation mechanisms of glycine and the crystal growth mechanisms for β-glycine respectively. The VOAG, a monodisperse droplet generators (MDG), is similar to small-scale spray driers; however, they provide specific advantages over spray drying technology in both control of droplet size and droplet environment. Monodisperse droplet generators lead to a narrow range of droplet distributions which avoids complications in using spray dryers such as inconsistencies in morphology and moisture content of the resulting particles.25,29 Additionally, the VOAG is designed to disperse the droplets from one another after their generation, allowing for microscopic isolation of each droplet leading to an enhanced drying rate. The rapid drying from MDGs has previously led to several studies focusing on the amorphous character of the


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formed particles, and comparatively little study on the crystallinity or more specifically polymorphism of the resulting particles. Nonetheless, recent work by this group has shown an example of this rapid drying leading to the preferential formation of metastable crystalline polymorphs, specifically for succinic acid, rather than amorphous structures.30 This work with glycine offers several important advantages over the previous work30. First, the previous work was only able to show a mixture of metastable and stable polymorph, whereas this work presents an opportunity to demonstrate pure metastable polymorph formation. Thus, with glycine being such a well-studied, polymorphic, organic molecular crystalline system it is ideal to consider as a second case for crystallization using monodisperse droplet generators. This can demonstrate that the effects are not specific to one specific solute, but rather potentially generalizable to many systems. Also, the choice of glycine allows for direct comparison to the products of spray drying glycine from water solutions which can provide insight into the mechanism driving the metastable polymorph formation that was not possible with the previous work. Further, there is potential in this work to demonstrate a larger impact on morphology since succinic acid already demonstrated a plate-like or blocky morphology, the differences in the resulting particles was limited. Finally, the results have the potential to provide a valuable data point for computational researchers interested in the underlying formation mechanism of the metastable β-glycine polymorph. The remainder of this work is outlined as follows. First, the materials and methods used to generate and analyze particles are described.

Next, the results for the overall particle

generation as well as the crystal polymorphism are presented and discussed. Then, the internal and external morphology (habit) of the glycine particles is presented, both as a function of solvent as well as in comparison to the morphology of glycine grown from other solution based processes. Finally, conclusions and implications for future work are discussed.


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Experimental Section

Solution and Sample Preparation Solutions are prepared using glycine (Alfa Aesar, 99+ %) as the solute and water, waterethanol mixtures, and water-acetone mixtures as the solvents. The water is obtained from a simplicity ultrapure water purification system (Millipore). Ethanol and acetone (Amresco, 99.5+ %) are used with no additional purifications. The solutions are prepared with solute concentration of 16.6 g/L in each solvent or solvent combination (the initial concentration was chosen as a balance between the desire for particles to be formed in the 10-20 micron size range with the need to stay below an initial droplet concentration of ~50% of the solubility limit, in all solvent mixtures, which can cause instrument clogging). Solvent ratios range from 0-30% by volume, at room temperature, of ethanol or acetone combined with water. All solutions are clarified with 0.45 µm FluoroporeTM filters (Millipore) before being introduced into the experimental equipment.

Crystallization in Evaporating Microscopic Droplets Particles are prepared through the evaporation of solution droplets created using a modified vibrating orifice aerosol generator (TSI, Inc., model 3450). The VOAG contains a syringe pump that leads to an orifice through which the solution flows. Through an externally applied frequency disturbance, the solution jet is broken up into nearly monodisperse droplets. For this work, the VOAG is operated with a 20 micron diameter orifice, resulting in an initial droplet diameter of ~46 microns. The dispersion air (~1500 cc/min) serves to disperse the


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droplets after formation and dilution air (~40L/min) provides for a constant supply of dry air for rapid droplet evaporation leading to glycine crystallization. The VOAG is operated using an inverted setup, with a six foot drying column. For a more detailed description as well as a diagram of the modified VOAG setup used here, see Carver and Snyder.30 The particle samples are collected at the base of the drying column on steel discs, sometimes with carbon tape, for morphology determination and on single crystal Si zero background sample disks (PANalytical) for structural analysis. The duration of the VOAG runs and concurrent collection is directly related to the density of particle collection desired for analysis and typically ranges between 30 (for particles that are relatively isolated from one another on the collection disc) and 120 minutes (for multiple layers of particles on a collection disc).

Characterization Particles are analyzed for both structure and morphology after they are collected at the bottom of the column. A scanning electron microscope (SEM) is used to image the samples, leading to an analysis of the particles’ morphology. Samples are analyzed using powder X-ray diffraction to collect data regarding the structure of the crystals. Samples are transported from the column to the X-ray diffractometer in a desiccating environment since β-glycine is known to be stable for long periods in dry environments, but polymorph conversion often occurs in a humid environment.11 For each of the structure, internal morphology and external morphology determinations respectively, the powder X-ray scans, particle breakage or gold coating for SEM analysis typically takes place within 20 minutes (enough time to disassemble the VOAG and transport the samples to the analysis instruments) of concluding a collection of particles. To view images using SEM, samples are collected on steel disks covered with carbon tape. To visualize the morphology directly from the experiment, a conductive gold coating is


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immediately applied to the samples via a gold sputter coater (Denton, Vacuum Desk IV). The resulting samples are viewed with a scanning electron microscope (JEOL, JSM-6390LV). To view the internal morphology of the particles, samples are first collected directly on steel disks.

The particles are then broken using either a 100-µm flat punch tip from a

nanoindenter (Hysitron, TI 950 TriboIndenter) or using the edge of a spatula.

Immediately

following application of the particle breakage techniques, samples are coated with a conductive layer as described previously then imaged with the SEM. For powder X-ray diffraction (PXRD), samples are collected on single crystal Si zero background sample disks (PANalytical). PXRD is performed using an x-ray diffraction system (PANalytical, PW 3040-X’pert Pro) operating at 40 kV and 45 mA. The step size and scanning rate are adjusted for individual samples to provide for high quality scan results, with typical scanning rates in the range of 3° to 5°, 2θ hr-1. The scanning range is chosen to highlight the region of interest for each of the glycine polymorphs. Resulting data are compared to predicted patterns (GLYCIN24 for α-glycine and GLYCIN27 for β-glycine) from the Cambridge Structural Database31.

Results and Discussion

In order to demonstrate the impact of monodisperse droplet evaporation on the polymorphism and morphology of glycine, first a typical monodisperse particle sample is presented. Then, the polymorphism of glycine, formed from water, water-ethanol and wateracetone solutions, is presented and discussed. Next, the morphology is compared to glycine obtained from a batch, anti-solvent crystallization.

Finally, both the internal and external


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morphology is presented and discussed as a function of the solvent choice and considered in relation to morphologies obtained for other solutes from monodisperse droplet evaporation. As seen in Figure 1 for a set of particles produced from water-ethanol solutions, the VOAG leads to relatively monodisperse particles of glycine, where a large majority of the particles are within 3-4 microns in diameter of one another. The degree of collection (density of the particles) seen in Figure 1 is typical of that obtained for trials to determine particle morphology or demonstrate monodispersity.

For the next section where polymorphism is

considered, significantly more particle collection is obtained while less collection is sometimes used to analyze the morphology of a single glycine particle.

Figure 1. SEM image for the collection of crystalline glycine particles grown via monodisperse droplet evaporation from an 80-20 volume %, water-ethanol solution. Lesser collection is typically obtained for morphology studies, while greater collection is obtained for crystal structure analysis.

Glycine Polymorphism from Droplet Evaporation Glycine particles were formed via monodisperse droplet evaporation from solutions with equal concentrations of glycine in water, water-ethanol mixtures and water-acetone mixtures. Ethanol and acetone are both anti-solvents for glycine which imposes a limit on the amount of each antisolvent present to maintain the same initial concentration and desired particle size. For this study, the maximum ethanol and acetone content in the solutions is therefore limited to 30%


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by volume. The crystallinity and polymorphism of the particles produced in each experiment using the solution concentrations provided in the methods is analyzed using PXRD and the results are highlighted in Figure 2. The PXRD results shown in Figure 2 using solvent mixtures are characteristic of all results in the range of solvent ratios considered. The results show that particles formed, regardless of solvent and even from pure water exclusively contain the metastable β polymorph.

Figure 2. Powder XRD patterns (a and b) simulated from the α and β polymorph crystal structures via the Cambridge Structural Database (GLYCIN24 and GLYCIN27 respectively) are compared with crystals obtained from monodisperse droplet evaporation of (c) glycine formed from pure water solutions, (d) glycine formed from 80-20 volume % water-ethanol solutions and (e) glycine formed from 70-30 volume % water acetone solutions. The β polymorph was exclusively obtained in each experiment, even for glycine from pure water solutions.

While the formation of the β polymorph is expected for the water-ethanol or wateracetone mixtures since at least some of the β polymorph forms in those same mixtures in milliliter and larger-sized batch crystallizations, the β polymorph is not generally found in typical


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crystallization experiments from pure water32. While the β polymorph previously was isolated in water solutions on the nanoscale (several dozen nm) through nano-confinement22, the size of these particles, on the order of several microns, demonstrates that they can be grown to a much larger size. They showed that the formation of the β polymorph at sizes of less than 25nm resulted in the β polymorph being stable for over a year. While the lack of residual solvent in the particles also allows our β glycine to be stable for at least a month in a dry (desiccated air) environment, it readily transforms to the α polymorph over the course of 24-48 hours at ambient conditions (e.g. relative humidity of 30%). Other previous work has shown that mixtures of the β and α polymorphs25 or only the α polymorph26 have been found from traditional spray drying, highlighting the importance of the monodisperesed droplets which are well separated from one another as considered in this work. While the droplet environment and formation process are more similar to that of spray drying, the results are more similar to those found from macromolecular emulsions of aqueous solutions;18 however, the droplet oil interface in that work is replaced with a droplet air interface in our work. The water-air interface alone does not tend to itself template the formation of β-glycine in other experiments where it is present (e.g. spray drying, cooling or evaporative crystallizations in a beaker).

Based upon our results in

consideration of previous work, the most likely mechanism to explain our isolation of the β polymorph is a combination of both isolated nucleation of the β polymorph exclusive of the α polymorph and the kinetic trapping of the resulting crystal. Both the isolated nucleation and kinetic trapping are made possible through the very rapid evaporation from droplets formed through the monodisperse droplet generator. Ostwald’s rule of stages suggests, and previous work has demonstrated for glycine, that the metastable polymorphs are formed first in solution. Since other microscopic methods, such as spray drying, have found that some β-glycine existed through other means of forming crystals while also having a significant presence of the α form, it


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is likely that we have been able to achieve two simultaneous features necessary to isolate the β polymorph. First, the efficient droplet dispersion and lower droplet production rates from the VOAG has likely led to a less humid air condition around each droplet (in comparison to a spray dryer).

This dryer air leads to rapid evaporation in our system driving a high enough

supersaturation to show an exclusive preference for the formation of the β polymorph over any others. Second, the solvent fully evaporates on a time scale fast enough that none of the α polymorph forms, since when the alpha form is present there is typically a rapid solventmediated phase transformation of β to α. This mechanism for isolating β-glycine, where higher evaporation rates lead to less stable polymorphs, is further supported by previous work showing the opposite trend for very slow evaporation of water from glycine solutions.33 In that work, the most stable γ-glycine polymorph was obtained through the evaporation of microdroplets over several hours. While this theory is not new in and of itself, it is important to note that the rate of generation of supersaturation can be the dominant feature in controlling the polymorphism of glycine superseding previously considered dominant features such as solvent.

Thus, this

represents further evidence that with an appropriate driving force, β-glycine can be exclusively formed from pure water solutions and grown to the micron scale without the formation of αglycine.

Further, among the many theories that currently are considered for glycine

nucleation,34-37 these results could be considered in validating their fidelity in particular as it relates to nucleation from aqueous solutions.

Morphology from Droplet Evaporation Compared to Bulk Since the glycine crystals formed via monodisperse droplet evaporation are exclusively the β polymorph even in pure water, a morphological comparison can be made to β-glycine formed through other methods.


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The crystal habit of β-glycine typically takes on a long rod or needle-like shape21,28 when obtained from water-ethanol solutions. Needle-like shapes are particularly problematic with regards to post processing steps such as filtering and drying, and the habit is often avoided when it is possible to stay within other constraints (e.g. maintaining the polymorph).38 Figure 3 shows the needle-like habit, grown from an antisolvent crystallization using water as the solvent and ethanol as the antisolvent in a batch crystallizer, compared to the external morphology obtained from a similar solvent concentration (90-10 volume % water-ethanol solution) for particles obtained through monodisperse droplet evaporation from the VOAG. The needle-like habit is similar to those seen in other work.

The crystalline, β-glycine particles formed from

monodisperse droplet evaporation takes on a rounded external morphology (which is commonplace through droplet evaporation); however, no aspects of the resulting particle have any needle-like properties. Rather, the particle appears to be made up of a series of sheets (each of which may represent one or more individual crystals) as opposed to needles. In both cases there is a very high driving force for crystallization; however, one explanation for the morphological differences could be that by the time the particle forms from droplet evaporation, the preferential evaporation of ethanol to water from the droplet, may have reduced the concentration of ethanol in the system to levels much lower than in the antisolvent crystallization. Nonetheless, since the β-glycine also is obtained from pure water solutions, monodisperse droplet evaporation produces β-glycine in more favorable non-needle-like morphologies.


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Figure 3. A comparison of the external morphology of β-glycine obtained from both (a) a 3 mL batch antisolvent crystallization (optical microscopy) and (b) monodisperse droplet evaporation from a pure water solution (SEM). The long needle-like habit seen in (a) is typical of the habit found from many experimental techniques while the spherical external morphology primarily considered in this work is potentially more desirable from a processing perspective. Note the small bipyramidal crystal in (a) is an α-glycine crystal.

Morphology from Droplet Evaporation as a Function of Solvent Particle morphologies from droplet evaporation take on a wide range of morphologies. Classification systems for those particles are available elsewhere

30,39-41

. Previous work of this

group demonstrated that in classifying the morphology, it is important to not only consider the external morphology, but also to consider an investigation of the morphology inside of the particle. The external morphology of β-glycine as a function of solvent, including pure water, water-ethanol mixtures and water-acetone mixtures, is shown in Figure 4. The particles grown from water and water-ethanol solutions have a shape displaying a series of layered (order 1 for every micron) slices throughout the particle.

The particles grown from water-acetone solutions,

based upon the outside of the particle seen in the images of Figure 4, appear to have a nearly solid shell surrounding the particle. However, in order to further understand each of these morphologies, studying the internal morphology through particle breakage is desired.


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Figure 4. SEM images of β-glycine obtained through monodisperse droplet evaporation from (a) pure water solution, (b) 95-5 volume % water-ethanol solution, (c) 90-10 volume % water-ethanol solution, (d) 70-30 volume % water-ethanol solution, (e) 95-5 volume % wateracetone solution (f) 90-10 volume % water-acetone solution, (g) 70-30 volume % water-acetone solution. All morphologies are similar in that they have a ridged structure; however, the ridging with water or water-ethanol as the originating solvent is distinctly larger than the ridging with water-acetone as the originating solvent. Note that the orientation of the image in (d) and (e) shows a location where nucleation may have begun in the particle. The top of the particle in (d) and about 5 microns left of the center of the particle in (e).

Figure 5 shows the result of breaking the β-glycine particles formed from water, waterethanol and water-acetone mixtures. The internal morphology of the particles formed from water and water-ethanol mixtures confirms the expectations from the images of unbroken particles. Indeed the particles are relatively solid other than the space left between the ridges which, as was seen in Figure 4, are approximately 1 micron in spacing. Looking at Figure 5, the internal morphology of the particles formed from water-acetone mixtures, reveals that the resulting cleavage when breaking these particles is actually very similar to those formed from water and water-ethanol mixtures. While the outside of the particle appears fairly solid, the resulting


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breakage planes indicate that the morphology may actually have much more closely stacked planes along the ridges of the particles seen in Figure 4. Thus, the impact of the solvent seems to be that adding acetone increases the density of the particles since there is little visible void space between any of the breakage planes in the particles formed from water-acetone mixtures. Increasing the amount of acetone or ethanol in the solvent mixture tends to increase the droplet evaporation rate. The addition of the ethanol does not seem to have any noticeable impact on the morphology in comparison to the pure water solvent whereas the addition of acetone does impact the morphology in comparison to the pure water solvent. Further, there is not a significant difference in the morphology when additional ethanol or acetone is added beyond the 10 volume percent. Based on these two facts, neither the difference in solubility (which decreases as ethanol or acetone volume percent is increased) or the evaporation rate (which increases as ethanol or acetone volume percent is increased) can explain the morphology differences. Thus, it is reasonable to conclude that the morphology differences seen in particles formed from the water-acetone solvent mixtures in comparison to the particles formed from the pure water solvent or water-ethanol solvent mixtures is likely due to solvent-solute interactions between the acetone and glycine.


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Figure 5. SEM images of broken β-glycine obtained through monodisperse droplet evaporation from (a-b) 90-10 volume % water-ethanol solution, (c-d) 90-10 volume % wateracetone solution. The noted ridging on the external aspects of the particles continues throughout the inside of the particle as well. The internal aspects of broken β-glycine particles are representative of all concentrations of the mixed solvents, and internal aspects of broken βglycine from water shows the same characteristics as that of β-glycine from the water-ethanol solutions.

Again, there does not appear to be any aspect of the typical needle-like morphology seen for β-glycine. The morphologies show some similarities to those formed from aqueous solutions in macromolecular emulsions;19 however, they did not break the particles to reveal the resulting overall morphology. Also, there was not as pronounced ridging of the particles as found in this work. The rapid formation of the particles in this work, potentially placed additional stress on the system which did not allow the crystals to completely fill the sphere in the particles from water and water-ethanol mixtures. Also, those particles did not contain as Most recently, other work has shown “brick-shaped” β-glycine crystals grown from solutions without additives for habit modification which is attributed to the influence of microscale physics.42 Along with the


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high levels of supersaturation, a similar importance of the microscale physics mechanism also explains the resulting morphologies in this work. Based on existing classification schemes for morphologies of particles formed from monodisperse droplet evaporation,30 the particles appear to be solid and slightly porous, with no shell surrounding the particle. Further, the particles appear to have a location on the surface where nucleation may have begun (see the top of the particle in Figure 4d and ~5 microns left of center in Figure 4e) with the remaining solute then crystallizing rapidly into the layer like structures from that location. Thus, the particles likely grew starting at one point on the outside of the droplet and quickly incorporated the remaining solute. This is consistent with the fact that rapid droplet evaporation would lead to a higher supersaturation at the surface of the droplet.

Conclusions Using monodisperse droplet evaporation is demonstrated to be a useful technique to investigate the structure and morphology of the resulting crystalline particles. Using glycine as the solute of interest, exclusively the β polymorph was found in all cases considered regardless of the solvent composition. It is particularly notable that β-glycine was formed from water solutions, in a droplet, on a micron scale with only an interface with air. This is particularly of note since similar experiments in a spray dryer with glycine in water solutions were not able to isolate β-glycine. Thus, we hypothesized the ability of the VOAG to both rapidly form the βglycine polymorph due to the relative isolation of the droplets in comparison to spray drying, and a resulting trapping of the pure β-glycine through complete solvent evaporation. Additionally, the resulting morphology of the particles showed an absence of needle-like structures typically seen for β-glycine crystals. Rather, the particles were porous and solid, containing sheet or platelike internal breakage planes, with the solid formation seeming to emanate from a location on the


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surface of the particle.

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Thus, the VOAG enabled a significant change in the external

morphology or habit of the system.

The characteristic spacing between breakage planes

significantly smaller, or even unnoticeable from an external view, for particles obtained from the water/acetone solution as compared to those obtained from the water or water/ethanol solutions. This work further demonstrated this technique as useful in exploring metastable polymorphs of other organic molecular compounds. Further, it could be used as a model system to consider particle formation methods with regards to morphology or the formation of amorphous structures.


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AUTHOR INFORMATION Corresponding Author *Phone: (570) 577-2346; e-mail: [email protected]

ACKNOWLEDGMENTS We thank the Bucknell University Geology Department for use of the X-ray diffractometer and Brad Jordan for his assistance with X-ray diffraction. Funding for D. I. Trauffer and A. K. Maassel was provided through the Bucknell Program for Undergraduate Research.


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For Table of Contents Use Only

Non-Needlelike Morphology of β-Glycine Particles Formed from Water Solutions via Monodisperse Droplet Evaporation David I. Trauffer, Anna K. Maassel and Ryan C. Snyder*

The impact of solvent or solvent mixture is shown for the formation of β-glycine via monodispersed droplet evaporation produced from a Vibrating Orifice Aerosol Generator (VOAG). Exclusively the β-glycine polymorph is formed even in pure water solutions, which is characteristically different than results generated through traditional spray drying.


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Non-Needle-like Morphology of Î²-Glycine Particles Formed from

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