(583d) Droplet to Particle Model Prediction By Coupling Solution Rheological Characterization, CFD and Phase Doppler Analysis

In the spray drying process, the rheological properties of the feed solution play a significant role on the droplet formation, coalescence and particle formation. The most used polymers in oral drug product formulations have influence on the viscosity of the feed solution and may contribute to a non-Newtonian behavior. During atomization, the feed solution is subjected to high shear rates (10^⁵ to 10^⁶ s^-1), which impacts the feed viscosity inside the nozzle. Thus, it is crucial to assess the rheological profiles and impact of the most used polymers at said conditions in order to better estimate the atomization profile and droplet size correlations.

Most common rheological analysis, such as rotational rheometry have a limited range of shear rates to be tested, with a maximum of 10^³ s^-1 shear stress (Figure A). To overcome this limitation, microfluidics rheological analysis can be performed to reach higher shear rates than standard analysis and without the solvent evaporation impact.

A database comprising the rheological characterization of standard polymers used in oral drug products was obtained using abovementioned rheological analysis. The effect of the polymer, concentration and solvent system on dynamic viscosity was studied to include typical shear rates observed in the nozzle orifice. Furthermore, by combining the rheological data with CFD modelling, it was possible to infer about feed pressure for a specific nozzle and flow rate, as can be seen in the Figure B. This allows for the prediction of unexpected outcomes and for the correction of the process parameters when working with formulations with a viscosity that interferes in the atomization. On the other hand, viscoelasticity studies (extensional rheometry) also provided information on key parameters (i.e. relaxation time) that directly correlates with polymer concentration and therefore will allow a more accurate prediction of droplet formation/size (Figure C).

By adding this data to modelling tools, the accuracy in the prediction of spray drying process parameters and droplet size will increase, as well as the confidence in scale-up and tech transfer processes – scale independent correlations i.e. droplet size vs Dv50. Furthermore, experimental tests using tools such as the phase-doppler can corroborate the optimized droplet size predictions and the correlation between the viscosity of the feed solution and the feed pressure (Figure - D).