The role of steam as a medium for droplet crystallization

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The role of steam as a medium for droplet crystallization Amanda Lum, Nicholas Cardamone, Ron Beliavski, Shahnaz Mansouri, Karen Hapgood, and Wai Woo Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/acs.iecr.9b00561 • Publication Date (Web): 23 Apr 2019 Downloaded from http://pubs.acs.org on April 23, 2019

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Industrial & Engineering Chemistry Research

The role of steam as a medium for droplet crystallization Amanda Lum a , Nicholas Cardamone a , Ron Beliavski a , Shahnaz Mansouri a , Karen Hapgood b , Meng Wai Woo a,c* a Department b School c Department

of Chemical Engineering, Monash University, Clayton, Victoria, Australia of Engineering, Deakin University, Waurn Ponds, Victoria, Australia

of Chemical and Materials Engineering, Faculty of Engineering, University of Auckland, Auckland, New Zealand *Corresponding email: [email protected]

ABSTRACT Mannitol and sodium chloride (NaCl) were spray dried using a counter current superheated spray dryer. Superheated steam was found to induce relatively high nucleation during the solidification of the sprayed droplets when compared to hot air. This allowed the production of spherical mannitol particles with very fine crystals at a lower temperature. In addition, superheated steam led to the formation of unique salt microspheres consisting of hollow hopper like sodium chloride crystal. These unique particle morphologies were not observed in hot air spray drying. Further analysis revealed that higher droplet temperature during the constant rate drying period, under superheated steam conditions, led to the high nucleation phenomenon. Results from this work illustrates the potential of superheated steam as a useful medium for in-situ crystallization control in spray dryers.

Keywords Spray drying; Superheated Steam Drying; Mannitol; Crystallisation; Surface Modification; Morphology

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1.0 INTRODUCTION Spray drying is a process widely used in the food and pharmaceutical industry as a one-step process to manufacture products in the particulate form. There has been considerable interest in the control of the crystallinity of powders produced from spray drying. Crystalline powder offers higher stability during storage.1,2 In addition, the different degrees or forms of crystallinity produced in the spraydried particles will further affect the functionality of the particles.3 There are various strategies proposed in the literature for the control of in-situ crystallization during the spray drying process. For fast to crystallize material (eg. mannitol which forms well defined crystals when spray dried), one strategy is to manipulate the drying rate of the droplets so that different degrees of super-saturation can be produced during the drying process, leading to different crystalline morphology.4,5 There has been a mix of reports in the literature proposing the manipulation of this drying behaviour by using different drying temperatures, controlled either by increasing or decreasing the inlet or outlet temperature of the spray dryer.4,5,6,7 Some workers in this area also suggest precise manipulation of the drying history, specifically controlling specific durations of the drying process. A theoretical framework was proposed by Feng et al.8 who suggested that crystallization can be controlled by manipulating the drying time for the droplet to reach supersaturation. In similar veins, Woo et al. 6 and Shakiba et al.7 suggested that insitu crystallization in spray drying is highly dependent only on the intermediate stage of the drying history. Manipulation of the local humidity within the chamber, by water mist injection, is one possible approach to control the intermediate stage of drying for crystallization. Along this line, there is also development of a narrow tube spray dryer technique to provide direct control of the drying history for crystallization control and study.9 For the spray drying of hard to crystallize materials (eg. lactose which typically forms amorphous particles in spray drying), the control of crystallinity based on the solid phase transition of particles within the spray dryer has been proposed.10,11,12 This approach mainly involves controlling the outlet temperature of the spray dryer or the humidity within the chamber such that there is sufficient plasticisation to the particles to induce solid phase transition. The glass transition theoretical framework forms the basis for this approach of crystallization control in spray dryers. While the strategies discussed above focused on the operation of the spray drying process, there are minimal reports on the manipulation of the drying medium as an avenue for crystallization control. Islam and Langrish evaluated the use of carbon dioxide as a potential drying medium for crystallization control (not to be mistaken for supercritical fluid processing).13 Woo et al. proposed the use of


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ethanol vapour or steam as the drying medium as the antisolvent vapour to precipitate water soluble and insoluble solute from within droplets in spray drying.14 Recently, in further exploration of superheated steam (SHS) as a drying medium for convective droplet drying, unexpectedly, the use of SHS led to a unique salt crystallization behaviour15. In that earlier report, SHS was found to be able to lead to relatively high nucleation rates during droplet solidification when compared to hot air drying at the same drying temperature. This was despite SHS exhibiting lower drying rates when compared to hot air drying (2.94 x 10-5 vs 1.08 x 10-4 kgm-1s-1, respectively). The higher nucleation rate was due to the droplet experiencing a high temperature during the constant rate drying period, corresponding to the saturation temperature, which leads to the in-situ crystallization phenomenon. Such higher temperature during the constant rate drying period was also previously observed to be the reason behind the higher propensity for browning when drying milk droplets with superheated steam.33 It is noteworthy that these early exploratory work on modifying the crystallization behaviour was done using the single droplet drying technique in which a relatively large droplet (thousands of microns) was suspended and dried at time scales of two order magnitude larger than that in a typical spray drying process (60 – 220 seconds). In view that crystallization is a time scale dependent phenomenon, there is a scientific need to evaluate if this high nucleating potential of SHS still manifests in an actual spray drying system in which the time scale is significantly shorter due to a smaller droplet length scale (tens or hundreds of microns). Therefore, this study aims to fill this gap in knowledge by using SHS as the drying medium to produce and control the crystallinity of spray dried particles via a lab scale spray dryer. Mannitol and NaCl were chosen as model materials representing organic sugar and ionic materials, which are fast to crystallize within the spray drying time scale. This work elucidates how SHS, which provides a significantly different droplet drying history when compared to hot air, will provide a wide potential for crystallization control in spray dryers.

2.0 MATERIALS AND METHOD 2.1 Materials Solutions of D - Mannitol (D-Mannitol, Sigma Aldrich) and Sodium Chloride, NaCl (Natural Rock Salt 99.8% NaCl, SAXA) at 15wt% were prepared by dissolving the crystalline material with miliQ water. Fifteen minutes of stirring was sufficient to ensure all the crystals were fully dissolved. The D-mannitol used was analysed with XRD, showing beta polymorph characteristics (Figure 3 and 4).



2.2 Spray Drying A counter current spray dryer was used in this work. Figure 1 shows the dimensions and schematic of the dryer. The counter current spray dryer allows the use of hot air or superheated steam as the drying medium. Key features of this dryer setup was a T-section, which allowed the switch between the drying medium (steam and the hot air) and an air heater (Compact Hot Air Blower, Techspan). The air heater in which the flow rate and the air temperature can be independently controlled were used to preheat the chamber for at least 30 minutes prior to switching to the superheated steam to condition the chamber for another 20 minutes before the drying takes place. Superheated steam was generated by superheating (via the inline pipe heating tapes shown in the figure) saturated steam from an ambient pressure steam generator. Prior to superheating, a T-shaped bend in the pipe with a bottom drain was designed to remove saturated droplets which are part of the saturated steam. This ensured that heat transfer from the downstream superheater was effectively utilized to superheat the vapour component of the saturated steam, minimizing the need to vaporize the droplet component of the saturated steam. Due to the difference in density (0.53 kg/m3 for SHS and 0.92 kg/m3 for air at 140oC) which led to different velocities within the drying chamber, much lower superheated steam flow of 1.4kg/hr was used as compared to hot air at 16 kg/h. Preliminary testing revealed that higher steam flow rates led to undesired full upward entrainment of the particles due to the counter current configuration of the spray drying tower. For each medium, two temperatures of 140 and 180 oC were used. This temperature range was selected to provide significantly different drying history to the spray dried droplets. Another unique feature of the counter current superheated steam spray dryer was that the outlet valve of the bottom of the conical section of the chamber and the top outlet valve from the chamber was opened to ambient air. The upwards moving drying medium will entrain a bit of ambient air into the chamber via the outlet at the bottom conical region. Spray dried products were collected via the bottom outlet; particles which settled downwards, not entrained by the upwards moving drying medium. The drying chamber was also wrapped with heating tapes and was insulated to ensure the chamber wall temperature was always kept above 100 oC to avoid condensation of steam within the column. There were two main purposes for bleeding open the bottom outlet valve of the chamber. Firstly, it allowed continuous collection of the product in ambient temperature condition to avoid overheating of the product. Secondly, the inward entrainment of ambient air was important to prevent the accumulation of steam at the conical region of the chamber leading to undesired condensation. Initial design with a heated conical and double block valves to allow periodic removals of the products did not prevent undesired condensation of the steam; hence the bottom valve had to be kept open to prevent steam accumulation at the bottom conical region.


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The reported superheated steam and hot air temperature reported in this work were measured via a thermocouple inserted into the axis of the chamber approximately 15 cm above the inlet bend. The feed solution was atomised from the top into droplets using a misting nozzle with an orifice dimeter of 0.1 mm with atomising pressure of 3 Bar. All the results reported here were repeated in triplicate.

2.3 X-ray powder diffraction (XRD) Characterisation X-ray diffraction (XRD) (Rigaku, MiniFlex 600 XRD) characterisation was carried out with Cu Kα radiation to identify the crystalline phases or polymorphs of the spray dried powder. The analysis was carried out in the range of 0–40° for Mannitol and 20 – 80o for salt as the main diffraction peaks of the materials from this study representing their crystalline phase can be observed within this range. The scanning speed was set at 2°/s to provide providing sufﬁcient detection and resolution for the materials. The XRD peaks obtained from the experiment were compared with its pure form as purchased.

2.4 Particle morphology The morphology and crystal patterns of spray dried mannitol and salt were analysed using scanning electron microscopy (SEM) (Phenom XL, Australia) at 5kV accelerating voltage. Sample powders were spread across adhesive carbon tapes fastened on the SEM sample holder and were coated with a thin layer of platinum metallic coating via a sputter coater prior to the image analysis.

3.0 RESULTS AND DISCUSSION 3.1 Mannitol drying and crystallization All the spray dried mannitol particles, regardless of the different drying medium, were spherical and was composed of agglomerated high aspect ratio (long) individual crystals.

Comparing the

morphology obtained at 180 oC, SHS produced significantly fine crystal grains relative to that produced via hot air (Figure 2). Although the same drying inlet temperature was used, this observation suggests that the droplets underwent different drying histories during solidification. The fine crystalline morphology via the SHS suggested a condition which induced a relatively high nucleation rate coupled by low crystal growth rate of the mannitol, during the drying process. Additional studies were performed at lower temperatures to further understand the effect of the SHS temperature on the morphology of the mannitol particles. Lowering the SHS drying temperature to 140 °C produced larger single grain crystals (Figure 2c) as compared to those dried at 180 oC SHS.



Drawing from conventional understanding reported in the literature from air drying, this was expected as lower drying temperature will provide lower drying rates thus lower supersaturation rates. The general understanding in the literature is that this will provide a longer duration during the solidification period for the growth of the crystalline grains.16,17 Preceding the growth dominated phase of the crystalline grains, the lower drying rate was also expected to lead to lower supersaturation during the solidification process leading to lower nucleation rates, hence less crystalline grains. Similar trends were obtained from the air drying runs. The unexpected observation was that the reduction in the air drying temperature led to more significant change in crystallization, resulting in large crystalline chunks (indication of lower initial nucleation rates) when compared to the long crystalline structure at the higher temperature (Figure 2a,b). This is an indication that the use of SHS in spray drying facilitates high material nucleation. In support of this possibility, another observation was that the 140 °C SHS run, which was expected to have a lower drying rate when compared to the 180 °C hot air run, produced crystalline grain sizes which were qualitatively comparable to that of the 180 °C hot air run. Overall, the crystalline edges and the grain morphology from the SHS runs were also more defined when compared to the hot air runs. All these evidences suggested that there are other factors, apart from the effect of drying rates, which affects the formation of the crystalline grains. This will be elucidated in the discussion section later. Mannitol powder produced via hot air and SHS revealed identical X-ray spectrums, indicating similar form of D-mannitol being produced by both mediums. A direct comparison between the powder Xray patterns of 3 different pure polymorphs (alpha, beta and delta) of D-mannitol showed the presence of a mixture of α and β-polymorphs within both air and SHS dried mannitol. The presence of characteristic peaks of 13.7 and 17.3 o2θ for the α-polymorph as well as 14.6 o2θ in β-polymorph in the spray dried product are aligned as reported in literature.18 Other peaks from the experimental powders as marked in Figure 2 also showed corresponding peaks to its pure β as well as α polymorph at 18.7, 25.1, 38.2 o2θ and 27.5, 34.1 o2θ respectively. The product of both drying mediums showed no signs of δ-polymorph with the absence of the characteristic peaks of 9.7 and 24.6 o2θ reported in the literature. Owing to the difference in molecular arrangements of the various polymorphic forms of D-mannitol, the FTIR spectra (Figure 4) of both spray dried mannitol also showed good correlations with those of α and β-polymorphs and were coherent with the XRD identifications. Both SHS and air-dried mannitol had corresponding peaks and deformations to those in pure α and β- polymorphs as indicated in Figure 3. Similarly, the FTIR spectrum of the commercial powder also showed agreement with the XRD interpretation of the existing β-polymorphs. Based on the general nucleation theory, the nucleation rate of polymorphic forms are highly dependent on various factors which includes temperature,


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supersaturation and interfacial tension. Some studies have shown that the nucleation of the more stable forms such as the δ-polymorph occurs generally at lower temperatures.19 Besides that, Cornel et al have also reported a supersaturation threshold at which above the threshold, the metastable α polymorphs would always nucleate first then transforms to β and subsequently the δ form.20 The high temperature conditions used in this study could have generated sufficient supersaturation and caused the nucleation of metastable forms such as α and β-polymorphs to dominate. Given the consistency between the XRD and FTIR analysis, SHS or air did not influence the final product polymorphs.

3.2 Salt drying and crystallization Salt particles produced from SHS spray drying displayed a mixture of particle morphologies. This was because of the wide range of droplet sizes produced from the nozzle atomizer. The different droplet sizes will exhibit different inertia, drag characteristics and evaporation behaviour, leading to different in-situ crystallization histories. Therefore, within the same experimental condition, a mixture of particle morphologies was obtained. Figure 5a illustrates the morphologies observed from the 180°C runs. One of the main structure observed was large cubic salt crystals, which are expected from the spray drying of salt (Figure 5b). Of particular interest was that hollow microsphere consisting of similar smaller cubic crystals salt microspheres were also observed. These microspheres resembled those reported in a patent by Tate & Lyle Ingredients Americas Llc (WO 2015015151 A1).21 In the reported patent, the spray dried particles were produced using a small (co-current) laboratory scale Buchi spray dryer. The key difference, when compared to the current work, is that the approach proposed by Tate and Lyle necessitated the spray drying of salt-organic binder mixtures, in which the organic binder functioned to hold the individual salt crystals into the spherical form. The current salt microspheres produced did not require the use of organic binders and utilized a counter current spray drying approach. During the droplet drying process, salt crystals may start forming on the surface of the droplet (due to surface solute enrichment). As the droplet evaporates, the precipitated crystal on the surface of the droplet will then be set and ‘locked’ into a spherical form following the shape of the progressively shrinking droplet. It is noteworthy that the cubic salt crystal microspheres observed in this work was not entirely hollow (with just a layer of outer crystal shell/crust) but also consist of cubic salt clustered within the particle core. Therefore, in addition to the precipitation of the crystals on the surface, salt crystals may also form within the droplet. In addition to these clustered cubic crystals individual cubic crystals were also observed (Figure 5b). Another unique morphology observed from the SHS runs were hopper like salt particles. These hopper like particles manifested in two forms. The first form was observed in relatively large single unit cubic salt crystals in which concentric hollow layers were formed within the cubic structure resembling



hollow hopper structure with distinct steps (Figure 5c). In an analogous manner, the second form of the hopper structure was hollow bi-pyramidal salt crystals with smooth surfaces, instead of distinct steps (Figure 5d). These bi-pyramidal salt crystals, which were relatively smaller when compared to the step-wise hopper structure, were found to manifest as microspheres of the bi-pyramidal crystals; although broken off individual crystals were also observed.

In all the bi-pyramidal crystal

microspheres examined, the hollow pyramid structure also seemed to be oriented on the surface of the microsphere. The consistency of this observation suggested that the formation of the hopper bipyramidal structure could be highly related to the direction in which moisture was removed (radially away from the droplet) during the drying process. In contrast, the formation of the step-wise structure in the single unit larger individual hopper like crystals (Figure 5c) seemed to occur on all faces of the cubic structure. These will be discussed in detail later in the manuscript. It is noteworthy that the formation of the bi-pyramidal salt crystals via spray drying has not been reported before in the literature, apart from our earlier report utilizing the SHS single droplet drying technique to convectively dry salt droplets to mimic SHS spray drying15. When the temperature of the SHS was reduced to 140 oC, similar observation was obtained where a mixture of particle morphologies were produced similar to those in Figure 5 (not shown here for brevity – refer to Supplementary Information). The main difference when compared to the high temperature runs was that the cubic crystalline structure became less distinct and the hollow bipyramidal structures had less indentation (less hollow). This is shown in Figure 5e. In fact, only small bi-pyramidal dents were observed in some cubic salt crystals. These observations seemed to suggest the occurrence of a transition phase between the formation of the solid cubic crystals and the hopper crystal structure (slight dent, bi-pyramid, distinct steps), where the transition may be dependent on the drying intensity. In the hot air-drying runs, only cubic salt structures were observed; no hopper like crystal structure was seen. Hollow microspheres formed by numerous individual cubic crystals were also observed as those from SHS (Figure 6a). A reduction of hot air temperature similarly resulted in the cubic crystal structures becoming less distinct as shown in Figure 6b. Despite the different morphologies observed, XRPD analysis on the SHS and air dried NaCl crystals resulted in similar diffraction spectrums, at both spray drying temperatures evaluated, as shown in Figure 7. This reveals that both spherical salt particles with discrete crystallites produced through air drying and the bi-pyramidal salt structures yield from SHS drying had the same basic crystalline structure.

The different morphologies observed were mainly different secondary crystalline

structures. This differences in the secondary crystalline structure was due to the different secondary nucleation rate of the same basic crystalline structure, induced by the different drying medium (will be discussed in Section 4.2). This observation lend more evidence to the transition theory eluded from


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the observations of the solid cubic crystals and the different forms of the hopper crystal structure (slight dent, bi-pyramid, distinct steps).

3.3 Understanding the drying rates of the different drying medium An important component of the proceeding discussion was to firstly determine the drying rates of the droplet under the different drying medium used. This will be useful to assess how the drying rates affect (or did not affect) the crystallization process. Taking the evaporation of pure water droplets as a basis and the actual drying medium flow rates used in the experiments, we computed the indicative evaporation rates of droplets within the drying chamber. The calculations of the droplet evaporation represented as the mass flux of water were carried out based off the reported work of Costa and Silva.22 Detailed calculations are given in the Supplementary Information. It was found that within the possible operating temperature range of the experimental rig used, the drying rate under SHS conditions will be consistently lower than that of hot air drying. This was mainly because of the lower mass flow rate of SHS used (1.4 kg/hr). Even if the mass flow rate of SHS was similar to that of hot air (16 kg/hr), the temperatures used in the experiment was below the inversion temperature (Supplementary Information). While these calculated drying rates are indicative and is not full reflection of the entire drying history, particularly for the falling rate period, it does give an indication of the drying rates at the constant rate period leading to the solidification or crystallization of the droplet. Slower droplet evaporation, which leads to a slower increase in droplet solute concentration, is generally expected to result in a low nucleation rate leading to the formation of larger mannitol crystals.23 Based on the analysis presented in Figure 8, in which SHS will exhibit significantly lower drying rates, SHS would have been expected to produce mannitol particle constituting fewer but larger crystals. Observations as previously discussed in Figure 2 revealed the opposite where the SHS dried particles was composed of finer crystals indicating higher rates of nucleation during crystallization. Hence, there must be other factors that led to such high nucleation conditions.

3.4 Effect of drying medium on the nucleation behaviour of droplets Apart from the differences in the drying rates, another main difference in drying history is the temperature experienced by the droplets during the constant rate period. It is well known from past reports on SHS drying, that the droplet will rapidly heat up to and will maintain at the saturation temperature (100°C in the current experiments – ambient pressure steam) throughout the constant



rate period, whereas in hot air, the droplet will maintain at the wet bulb temperature (44oC and 49oC, approximated for the 140°C and 180°C runs, respectively). Nucleation rates of mannitol and other materials is known to positively correlate with temperature.23,24 The higher temperature during the constant rate period could have accelerated the nucleation rate during the solidification process. Even if the solidified droplets were to approach the same temperature towards the end of the drying process (if the same inlet temperature was used) or if the droplets were to achieve supersaturation at different drying time (due to the different temperature and evaporation history), the superheated steam environment would have induced a higher droplet temperature throughout the drying history. Similar phenomenon was also observed from the salt particle experiments. The observation of the hopper like structure only under SHS condition (Figure 5) is a direct indication of a high nucleation environment during dehydration, despite the lower drying rate. Hopper growth was reported in the literature from cooling crystallization experiments at conditions of high secondary nucleation.25,26,27 The formation of the hopper structure can be further explained by the Berg effect in which secondary nucleation will firstly occur at the edge of the initial cubic crystallite, due to exposure to a greater volume of the mother liquor, which then grows inwards across the cubic face.28 Hollow hopper structures are then formed from an additive manner by a competing rate of inwards face covering growth and the rate of addition of new crystal layers starting from the edge of the cubic face (Figure 9). In these past reports, the high secondary nucleation environment which is the basis for the hopper structure formation, was produced by using relatively high supersaturation.25,29,30 Because of the lower drying rate of the SHS, the supersaturation of the solute in the droplets would have been lower when compared to the air-drying runs.

Therefore, the relatively high droplet temperature

(corresponding to the saturation temperature of the steam) during the constant rate period would have then been the only factor increasing the nucleation rate during the dehydration process leading to the formation of the hopper structure. In view that similar observations were also obtained in the SHS single droplet drying experiments with salt droplets15 (single droplet drying time scale in the order of minutes, while the current drying time scale is in the order of seconds or fraction of second), this high nucleation phenomenon in SHS is not rate or process time scale dependent. From the discussion above, this is because the key to such high nucleating condition is the relatively high steam saturation (boiling) temperature which is an inherent physical characteristic of steam. This theoretical framework also explains why the hopper structure of the individual crystals of the hopper microsphere (Figure 5d) was outward facing. As the cubic salt particle crystallizes on the surface of the droplet, only the outer facing side of the crystal will have sufficient supersaturation due to the droplet surface enrichment during rapid evaporation (and the high droplet temperature) leading to the additive formation of the hopper structure. For the relatively large step-wise hopper


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like crystals (Figure 5c), the large size of the crystal indicates that the crystal was formed individually within the droplet in contrast to the precipitation as crystals on the droplet surface. Therefore, the formation of the hopper structure occurred in all the faces of the cubic structure instead of only one side of the crystal. This use of SHS will offer a non-chemical based avenue for such manipulation of salt crystal morphology. There are reports in the literature utilizing the addition of organic ligands and other additives to produce similar hopper like salt structure (Zhang et al30,31 and Qin et al32). It was claimed that the chemical based approach used a different type of mechanism which inhibits the growth rates specific plane in the crystallizing salt nuclei. This is in contrast to the additive mechanism responsible for the hopper morphology obtained from SHS spray drying. The steam saturation temperature, which is the key to the unique in-situ droplet crystallization temperature in superheated steam, is a thermodynamic property of steam, which is directly related to the steam pressure. One way to control the crystallization process would then be to vary the steam pressure (also changing the chamber pressure) to result in different steam saturation temperatures. Coupled with the possibility of using different degree of superheating at different chamber pressures, it will be of interest for future work to evaluate different combinations of ‘crystallization’ temperature (delineated by the steam saturation temperature) and the drying rate (delineated by the degree of steam superheating) on the in-situ crystallization behaviour. Along the line of varying the possible drying rates, one possible approach is for further evaluation using a co-current drying configuration. The same mechanism leading to different in-situ crystallization behaviour will still apply, as the steam saturation temperature is a characteristic of superheated steam independent of the drying configurations. The only differences expected in a co-current configuration are: (1) shorter total drying time and (3) higher wet bulb drying temperature; both differences are due to the initial contact of the droplets with a hotter drying medium in the co-current configuration. How these two differences in the drying history augments the significance of the drying medium on the in-situ crystallization will need to be determined experimentally in a co-current superheated steam/hot air spray drying facility.

4.0 CONCLUSION Mannitol and salt particles were produced with a counter current spray dryer using SHS and hot air as the drying media. When compared to hot air, SHS produced particles which was composed of finer crystals. This showed that SHS had the potential to generate relatively higher nucleation of the solutes in the droplet during drying despite providing a slower drying rate in the current experiments.



Superheated steam spray drying of salt (NaCl) in both air and SHS condition led to the formation of hollow microspheres composed of individual cubic crystals. However, drying under SHS led to the formation of a unique hollow hopper like salt crystal structures which was not observed in hot air. This suggest that SHS can be used to manipulate crystals formations during drying and thus offers a potential cleaner non-chemical avenue for crystal manipulation when compared to the approaches available in the literature. Results from this work contributes to further understanding of the effect of SHS on the formation of crystals from droplets and thus illustrates the potential use of SHS as a useful medium for crystallization control to potentially engineer specific crystal structures in spray drying.

5.0 ACKNOWLEDGEMENT The first author would like to acknowledge the scholarship support from Monash University. Special thanks to Professor Sakamon Devahastin (King Mongkut University of Technology Thonburi) for the idea on the separation of the saturated steam droplets prior to superheating.

6.0 SUPPORTING INFORMATION Calculations to estimate and compare drying rates within the drying chamber under different drying mediums. SEM images of particles from the low temperature superheated steam experiments.

7.0 REFERENCES (1) Vehring, R. Pharmaceutical Particle Engineering via Spray Drying. Pharm. Res. 2008, 25, 999. (2) Costantino, H.R.; Andya, J.D.; Nguyen, P.A.; Dasovich, N.; Sweeney, T.D.; Shire, S.J.; Hsu, C.C.; Maa, Y.F. Effect of Mannitol Crystallization on the Stability and Aerosol Performance of a SprayDried Pharmaceutical Protein, Recombinant Humanized anti-IgE Monoclonal Antibody. J. Pharm. Sci. 1998, 87, 1406. (3) Burger, A.; Henck, J.O.; Hetz, S.; Rollinger, J.M.; Weissnicht, A.A.; Stöttner, H. Energy/temperature diagram and compression behavior of the polymorphs of D-mannitol. J. Pharm. Sci. 2000, 89, 457. (4) Buckton, G.; Chidavaenzi, O.C.; Koosha, F. The effect of spray-drying feed temperature and subsequent crystallization conditions on the physical form of lactose. AAPS PharmSciTech 2002, 3, 1. (5) Chidavaenzi, O.C.; Buckton, G.; Koosha, F. The impact of feed temperature on the polymorphic content of spray dried lactose. J. Pharm. Pharmacol 2011, 50, 184. (6) Woo, M.W.; Lee, M.G.; Shakiba, S.; Mansouri, S. Controlling in situ crystallization of pharmaceutical particles within the spray dryer. Expert Opin Drug Del. 2017, 14, 1315.


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(7) Shakiba, S.; Mansouri, S.; Selomulya, C.; Woo, M.W. In-situ crystallization of particles in a counter-current spray dryer. Adv. Powder Technol 2016, 27, 2299. (8) Feng, A.L.; Boraey, M.A.; Gwin, M.A.; Finlay, P.R.; Kuehl, P.J.; Vehring, R. Mechanistic models facilitate efficient development of leucine containing microparticles for pulmonary drug delivery. Int. J. Pharm. 2011, 409, 156. (9) Lee, M.G.; Mansouri, J.P.; Mansouri, S.; Hapgood, K.; Woo, M.W. New narrow tube spray dryer for precise drying history control. Drying Technol. 2018, 36, 178. (10) Islam, M.I.U.; Langrish, T.A.G.; Chiou, D. Particle crystallization during spray drying in humid air. J. Food Eng. 2010, 99, 55. (11) Islam, M.I.U.; Langrish, T.A.G. An investigation into lactose crystallization under high temperature conditions during spray drying. Food Res. Int. 2010, 43, 46. (12) Woo, M.W.; Rogers, S.; Selomulya, C.; Chen, X.D. Particle drying and crystallization characteristics in a low velocity concurrent pilot scale spray drying tower. Powder Technol. 2012, 223, 39. (13) Islam, M.I.U.; Langrish, T.A.G. The Effect of Different Atomizing Gases and Drying Media on the Crystallization Behavior of Spray-Dried Powders. Drying Technol 2010, 28, 1035. (14) Woo, M.W.; Mansouri, S.; Chen, X.D. Antisolvent vapor precipitation: the future of pulmonary drug delivery particle production? Expert Opin. Drug Del. 2014, 11, 307. (15) Lum, A.; Cardamone, N.; Beliavski, R.; Mansouri, S.; Hapgood, K.; Woo, M.W. Unusual drying behaviour of droplets containing organic and inorganic solutes in superheated steam. J. Food Eng. 2019, 244, 64. (16) Earle, R.L. Chapter 9: Contact Equilibrium Separation Processes, Unit Operations in Food Processing, Elsevier, 20132013, pp. 116. (17) Choudhury, M.D.; Dutta, T.; Tarafdar, S. Growth kinetics of NaCl crystals in a drying drop of gelatin: transition from faceted to dendritic growth. Soft Matter 2015, 11, 6938. (18) Nunes, C.; Suryanarayanan, R.; Botez, C. E.; Stephens, P. W. Characterization and crystal structure of D-mannitol hemihydrate. J. Pharm. Sci. 2004, 93, 2800. (19) Lee, E.H. A practical guide to pharmaceutical polymorph screening & selection. Asian J. Pharm. Sci. 2014, 9, 163. (20) Cornel, J.; Kidambi, P.; Mazzotti, M. Precipitation and Transformation of the Three Polymorphs of d-Mannitol. Ind. Eng. Chem. Res. 2010, 49, 5854. (21) Shen, A.J.H.; Butler, S. Method of producing salt composition, WO 2015015151 A1, Tate & Lyle Ingredients Americas Llc, Tate & Lyle Technology Limited, 2015.



(22) Costa, V.A.F.; Neto da Silva, F. On the rate of evaporation of water into a stream of dry air, humidified air and superheated steam, and the inversion temperature. Int. J. Heat Mass Transf. 2003, 46, 3717. (23) Littringer, E.M.; Paus, R.; Mescher, A.; Schroettner, H.; Walzel, P.; Urbanetz, N.A. The morphology of spray dried mannitol particles — The vital importance of droplet size. Powder Technol. 2013, 239, 162. (24) Judge, R.A.; Jacobs, R.S.; Frazier, T.; Snell, E.H.; Pusey, M.L. The Effect of Temperature and Solution pH on the Nucleation of Tetragonal Lysozyme Crystals. Biophysical J. 1999, 77, 1585. (25) Desarnaud, J.; Derluyn, H.; Carmeliet, J.; Bonn, D.; Shahidzadeh, N. Hopper Growth of Salt Crystals. J. Phys. Chem. Lett. 2018, 9, 2961. (26) Sunagawa, I. Growth and Morphology of Crystals, Forma 1999, 14, 147. (27) Scheel, H.J. Developments in crystal growth from high-temperature solutions. Prog. Crystal Growth Charac. 1982, 5, 277. (28) Berg, W.F. Crystal growth from solutions, Proceedings of the Royal Society of London. Series A Mathematical and Physical Sciences 1938, 164, 79. (29) Yan, S.; Xie, C.; Zhang, X.; Zhou, L.; Hou, B.; Huang, J.; Zhou, L.; Yin, Q. Influence of Crystal Growth Conditions on Formation of Macroscopic Inclusions inside Thiourea Crystals. ChemistrySelect 2018, 3, 2293. (30) Zhang, J.; Zhang, Z.; Ji, Q.; Jiang, Y.; Zhang, S.; Wang, Z. General Strategy for Fine Manipulating Crystal Growth of Water-Soluble Salts. Crystal Growth & Des. 2014, 14, 1520. (31) Zhang, J.; Zhang, S.; Wang, Z.; Zhang, Z.; Wang, S.; Wang, S. Hopper-Like Single Crystals of Sodium Chloride Grown at the Interface of Metastable Water Droplets. Angewandte Chemie 2011, 50, 6044. (32) Qin, Y.; Yu, D.; Zhou, J. DNA action on the growth and habit modification of NaCl crystals. CrystEngComm 2017, 19, 5356. (33) Lum, A.; Mansouri, S.; Hapgood, K.; Woo, M.W. Single droplet drying of milk in air and superheated steam: particle formation and wettability. Drying Technol. 2018, 36, 1802.


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0.32m Spray Nozzle

Thermocouples

3.1m

Heating Tapes T-Connector

Drying Medium Inlet

Collection Valve

Figure 1: Schematic diagram of the lab scale counter current spray drying design.



(a)

100 µm

30 µm

(b)

110 µm

50 µm

170 µm

50 µm

140 µm

50 µm

(c)

(d)

Figure 2: SEM micrographs of D-Mannitol spray dried at under (a) Hot air at 140 oC (b) Hot air at 180 oC, (c) Superheated steam at 140 oC and (d) Superheated steam at 180 oC


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Alpha Form

*

*

#

Beta Form #

#

#

Sigma Form #

Commercial

#

# #

SHS Dried #

*

*

#

#

Air Dried # #

0

10

20

*

* 30

40

Figure 3: XRPD of pure polymorphs, commercial and spray dried D-Mannitol and under superheated steam and hot air at 180 oC



*

*

* Alpha Form

#

#

#

Beta Form

Sigma Form #

#

#

#

#

Commercial

*

*

*

#

* 1400

#

SHS

#

*

* 1200

1000

#

Air 800

Figure 4: FTIR Spectrum of various form of mannitol polymorphs, commercial and spray dried under superheated steam and hot air at 180 oC


Page 18 of 24

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30 µm

30 µm

(c)

(b)

100 µm

(d) Reduced SHS temperature

300 µm

30 µm

(e)

(a)

Figure 5: Different salt morphologies obtained from SHS drying at 180°C: (a) Overall view of the SEM sample containing a mixture of morphologies, which includes (b) microspheres of cubic salt crystals and large single crystals, (c) large concentric hopper like crystals and (d) microspheres of by-pyramidal hopper like crystals. When the steam temperature was reduced to 140°C, (e) illustrates the relatively shallow by-pyramidal hopper structure observed; resembling more of slightly indented cubic crystals.



80 µm

50 µm

(a)

(b)

Figure 6: Salt morphologies obtained from hot air drying at: (a) 180°C in which microsphere of distinct cubic structure was obtained, (b) 140°C in which the cubic crystals of the microsphere became less distinct.


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Air SHS Database

Intensity/cps

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


(200) (220) (111) 20

25

30

35

40

45

50

(222)

(400)

55

65

60

70

(420) 75



2( )

Figure 7: Comparison of XRD pattern of NaCl dried under air and SHS dried at 180 oC as well as those reported in the literature


80


Figure 8: Theoretical comparison of the droplet drying rates under SHS and hot air conditions in the spray tower.


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Figure 9: Growth pattern of hopper formation where new layers will start to nucleate and develop at the subsequent edges before the underlying layers is fully formed.



The role of steam as a medium for droplet crystallization Amanda Lum a , Nicholas Cardamone a , Ron Beliavski a , Shahnaz Mansouri a , Karen Hapgood b , Meng Wai Woo a,c* a

Department of Chemical Engineering, Monash University, Clayton, Victoria, Australia b

c

School of Engineering, Deakin University, Waurn Ponds, Victoria, Australia

Department of Chemical and Materials Engineering, Faculty of Engineering, University of Auckland, Auckland, New Zealand *Corresponding email: [email protected]

For Table of Contents only

Hot air spray drying

Superheated steam spray drying

S1 ACS Paragon Plus Environment

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The role of steam as a medium for droplet crystallization

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