(641f) Modeling the Steady State of a Spray Drying Unit with Drying Gas Recirculation Accounting for Complex Thermodynamics Using Sequential Simulation

Solid dispersions are a way to aid the solubilization of molecules that are poorly soluble in water, and hence make them a candidate to be dosed orally. These intermediate materials are manufactured by spray drying a mixture of a chosen solvent(s), a polymer, and the drug [1]. Several modeling approaches have been proposed to address the drying dynamics in the spray drying unit. Ranging from the empirical model approaches [1] to the use of dimensional and dimensionless numbers [2], to bulk modeling approaches [3] to detailed models that incorporate the droplet level mechanisms [4] and complex measurement systems [5].

The reality of the industrial practice of developing a spray drying process is far from the well instrumented experimental settings in academia. The only real-time measurements available are those of the bulk (for both process and materials). Benchtop tests provide data of the state of materials at equilibrium (e.g. adsorption data generated by a dynamic vapor sorption instrument) however these will not account for the kinetics. As of the time of this work, acoustic droplet levitation technology remains mostly an academic asset and is not a common testing instrument found in industry. As such, the kinetics of drying (although important for particle morphology) remain an unobservable phenomenon given the bulk measurements available. Additionally, from a regulatory standpoint, the definition of process parameters for spray drying (operating conditions the process would be registered at) refer to static conditions representative of the steady state, assuming the process is in a state of control.

In the absence of particulate level information, practice is to control the environmental conditions of the process, with the assumption that keeping these in control will result in product quality control. This is common in granulation and coating processes where thermodynamic conditions as used as a surrogate to controlling the unobservable phenomena happening at the particulate or droplet level. This thermodynamic environment in the drying chamber of a spray drying unit is one of the main control mechanisms for the drying phenomena (aside from the atomization) and requires careful consideration of the way the physical properties of the gas phase are calculated.

This work presents the development and use of a steady state model for spray drying using Aspen Plus (Aspen Technology Inc.), accounting for complex thermodynamics and accommodating the different control schemes in the units. The details of the development of the flowsheet will be described, including the adjustments of the numerical method used by the simulator, necessary to solve the flowsheet.

[1] Friesen, D.T., Shanker, R., Crew, M., Smithey, D.T., Curatolo, W.J. and Nightingale, J.A.S., 2008. Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview. Molecular pharmaceutics, 5(6), pp.1003-1019.

[2] Garcia-Munoz, S. and Settell, D., 2009. Application of multivariate latent variable modeling to pilot-scale spray drying monitoring and fault detection: monitoring with fundamental knowledge. Computers & Chemical Engineering, 33(12), pp.2106-2110.

[3] Dobry, D.E., Settell, D.M., Baumann, J.M., Ray, R.J., Graham, L.J. and Beyerinck, R.A., 2009. A model-based methodology for spray-drying process development. Journal of pharmaceutical innovation, 4(3), pp.133-142.

[4] Oakley, David E. "Spray dryer modeling in theory and practice." Drying Technology 22, no. 6 (2004): 1371-1402.

[5] Schiffter, H. and Lee, G., 2007. Single-droplet evaporation kinetics and particle formation in an acoustic levitator. Part 1: Evaporation of water microdroplets assessed using boundary-layer and acoustic levitation theories. Journal of pharmaceutical sciences, 96(9), pp.2274-2283.

[6] Radnik, J., Bentrup, U., Leiterer, J., Brückner, A. and Emmerling, F., 2011. Levitated droplets as model system for spray drying of complex oxides: A simultaneous in situ X-ray diffraction/Raman study. Chemistry of Materials, 23(24), pp.5425-5431.