(M1030-06-34) Experimental and Theoretical Investigation of Rotary Atomization Dynamics for Control of Lipid Multiparticulate (LMP) Particle Size during Spray Congealing Process

Purpose: Rotary atomization has been employed in the pharmaceutical industry to produce LMPs via the rotary spray congealing process. This process is useful owing to its capacity to effectively process a wide range of formulations, achieve a broad range of release kinetics, and for its ability to controllably produce microspheres of a range of sizes with narrow distributions. Particle size control is directly related to atomization and is considered a critical-to-quality attribute, i.e., particle size is critical to performance attributes such as the drug release rate and downstream processing. Therefore, the objective of this study was to investigate the rotary atomization dynamics to gain a fundamental and cohesive understanding of the mechanisms that influence particle size; and to compare the results with respect to previously published predictive models, thus allowing for the extraction of accurate predictions and the development of a robust process.

Methods: predictive models, thus allowing for the extraction of accurate predictions and the development of a robust process. Two pharmaceutically representative model systems, an inviscid fluid and a high-loaded suspension, were used to carry out the experiments. They were conducted on a custom-fabricated, lab-scale melt-spray-congeal (MSC) unit equipped with a rotary disk atomizer. High speed images of the atomization process were captured with a Phantom v7.3 high-speed camera, and particle size was analyzed via laser light scattering. To explore a broad process space, the disk speed and flow rate were the main control handles.

Results: Figure 1 exhibits the Frost [1] atomization regime space for inviscid fluids overlaid with experimental observations labeled with D50 particle size. In general, the regime predictions are in good agreement, with the exception of the transitional and direct drop regimes. Furthermore, the particle size is dependent on the atomization regime. The direct drop regime created droplets larger than those of the ligament regime for a given disk speed, and with a bimodal distribution; whereas the ligament regime created droplets that were uniform and narrow in distribution. Lastly, particle size models were developed from existing literature. Modifying equations from Liu et al. [4] and Kitamura et al. [6] by adding a slope and offset and minimizing the error, the particle size for direct drop and ligament regimes can be well predicted. Illustrated by Figure 2 are the presence of standing and radially propagating wave film instabilities in inviscid fluids. Standing waves are created when the nozzle is eccentric to the disk center. These waves, when exiting the disk, create larger particles than the rest of the ligaments, thus skewing the particle size distribution. Radially propagating waves are created by Kelvin–Helmholtz instabilities and observed at the higher disk speeds and flow rates. These waves also influence the resultant particle size distribution by creating larger droplets. Figure 3 illustrates the Frost [1] regime predictions overlaid with the experimental results and D50 particle size for suspensions. Suspensions don’t encompass the Frost regime space and behave differently than inviscid fluids. The suspended particles aid in the breakup by creating perforations that dominate atomization and thus, effectively suppress the sheet regime and expand the ideal operating space. Furthermore, the particle size can be predicted by a single modified equation from Kitamura et al. [6].

Conclusion: In summary, experiments were conducted using model formulations that encompass inviscid fluids and suspensions with respect to the melt-spray-congeal process. This study determined the atomization dynamics and its influence on the quality attribute of particle size to design a robust process with accurate particle size control. The experimental atomization regimes were identified and cross referenced with existing literature, the ideal operating range was identified, predictive particle size models were developed, and a framework for designing a robust MSC process across a range of formulations was outlined.

References: 5.1 A.R. Frost, Rotary atomization in the ligament formation mode, J. Agric. Eng. Res. 26(1) (1981) 63–78. https://doi.org/10.1016/0021-8634(81)90127-X.
5.2 A. Mahmoud, M. S. Youssef, Characteristics of mean droplet size produced by spinning disk atomizers, J. Fluids Eng. 134(7) (2012) 071103. https://dx.doi.org/10.1115/1.4006819.
5.3 A. Mahmoud, M. S. Youssef, Influence of spinning cup and disk atomizer configurations on droplet size and velocity characteristics, Chem. Eng. Sci. 107 (2014) 149–157. https://dx.doi.org/10.1016/j.ces.2013.12.004.
5.4 J. Liu, Q. Yu, Experimental investigation of liquid disintegration by rotary cups, Chem. Eng. Sci. 73 (2012) 44–50. https://dx.doi.org/10.1016/j.ces.2012.01.010.
5.5 V.T. Mantripragada, S. Sarkar, Prediction of drop size from liquid film thickness during rotary disc atomization process, Chem. Eng. Sci. 158 (2016). https://dx.doi.org/10.1016/j.ces.2016.10.027.
5.6 Y. Kitamura, T. Takahashi, Atomization of highly viscous liquids by a spinning disk, At. Sprays 2(1) (1992) 61–71. https://dx.doi.org/10.1615/AtomizSpr.v2.i1.50.
5.7 E. Teunou, D. Poncelet, Rotary disc atomization for microencapsulation applications–predictions of the particle trajectories, J. Food Eng. 71(4) (2005) 345–353. https://dx.doi.org/10.1016/j.jfoodeng.2004.10.048.
5.8 M. Mackaplow, I.E. Zarraga, J.F. Morris, Rotary spray congealing of a suspension: effect of disk speed and dispersed particle properties, J. Microencapsul. 23(7) (2015) 793–809. https://dx.doi.org/10.1080/09687860600945446.
5.9 W.H. Walton, W.C. Prewett, The production of sprays and mists of uniform drop size by means of spinning disc type sprayers, Proc. Phys. Soc. A 62(6) (1949) (341). https://dx.doi.org/10.1088/0370-1301/62/6/301.
5.10 Y. Senuma, J. Hilborn, High speed imaging of drop formation from low viscosity liquids and polymer melts in spinning disk atomization, Polym. Eng. Sci. 42(5) (2002) 969–982. https://dx.doi.org/10.1002/pen.11006.
5.11 T. Kamiya, A. Kayano, Film type disintegration by rotating disk, J. Chem. Eng. Japan 5(2) (1970) 174–182. https://dx.doi.org/10.1252/jcej.5.174.
5.12 Vita, B.F.W. Gschaider, D. Prieling, H. Steiner, Thin film flow simulation on a rotating disc, in: ECCOMAS 2012 - Eur. Congr. Comput. Methods Appl. Sci. Eng. E-B. Full Pap., 2012: pp. 2590–2600.
5.13 G. Leneweit, K.G. Roesne, R. Koehler, Surface instabilities of thin liquid film flow on a rotating disk, Exp. Fluids 26(1) (1999) 75–85. https://dx.doi.org/10.1007/s003480050266.
5.14 G. Sisoev, D. Goldgof, Valentina N. Korzhova, Stationary spiral waves in film flow over a spinning disk, Phys. Fluids 22(5) (2010) 052106.
5.15 S. Thomas, A. Faghri. W. Hankey, Experimental analysis and flow visualization of a thin liquid film on a stationary and rotating disk, J. Fluids Eng. 113(1) (1991). https://dx.doi.org/10.1115/1.2926500.
5.16 B. Ozar, B.M. Cetegen, A. Faghri, Experiments on the flow of a thin liquid film over a horizontal stationary and rotating disk surface, Exp. Fluids 34(5) (2003). https://dx.doi.org/10.1007/s00348-002-0572-y.
5.17 M. Freystein, T. Borsdorf, T. Gambaryan-Roisman, Peter Stephan, Experimental investigation of dynamics and atomization of a liquid film flowing over a spinning disk, At. Sprays 23(7) (2013) 619–633. https://dx.doi.org/10.1615/AtomizSpr.2013006704.
5.18 E. Villermaux, C. Clanet, Life of a flapping liquid sheet, J. Fluid Mech. 462 (2002) 341–363. https://dx.doi.org/10.1017/S0022112002008376.
5.19 N. Bremond, C. Clanet, E. Villermaux, Atomization of undulating liquid sheets, J. Fluid Mech. 585 (2007) 421–456. https://dx.doi.org/10.1017/S0022112007006775.
5.20 B. Mulhem, G. Schulte, A.A. Ali, Effect of solid particles on breakup of suspension sheets (2017).
5.21 L. Rayleigh, On the instability of jets (1878). https://doi.org/10.1112/PLMS%2FS1-10.1.4.
5.22 D.J. Ryley, Analysis of a polydisperse aqueous spray from a high-speed spinning disk atomizer, Br. J. Appl. Phys. 10(4) (2002) 180. https://dx.doi.org/10.1088/0508-3443/10/4/306.
5.23 A. Kayano, T. Kamiya, Calculation of the mean size of droplets purged from the rotating disc, Proc. 1st Int. Conf. on Liquid Atomization-Spray Systems, Tokyo, pp. 133–138.
5.24 H. Peng, N. Wang, D. Wang, X. Lin, Experimental study on the critical characteristics of liquid atomization by spinning disk, Ind. Eng. Chem. Res. 55(21) (2016). https://dx.doi.org/10.1021/acs.iecr.6b00401.
5.25 N. Dombrowski, R.P. Fraser, A photographic investigation into the disintegration of liquid sheets, Proc. Math. Phys. Eng. Sci. 247(924) (1954) 101–130.

Figure 1: Atomization regime space, as predicted by Frost, overlaid with experimental results. The open circles represent direct drop, plus symbols represent transitional, asteriks symbols represent ligament, x symbols represent a sheet, and the white numbers indicate the D50 particle size. The bottom graph displays the particle size results for each flow rate with respect to the disk speed.



Figure 2: Film instabilities in inviscid fluids (left: standing waves, and right: radially propagating waves)



Figure 3: Predicted atomization regime space for a suspension with the resultant D50 particle-size. The bottom graph displays the particle size results for each flow rate with respect to the disk speed.