(82d) Model Aided Scale-up of Spray Drying for a Sticky API (low Glass Transition Temperature)

Spray drying can be used to generate very fine powders for inhalable drugs and to improve the bioavailability of solid dosage drugs using amorphous solid dispersion. However, spray drying is quite a challenging process to optimize and scale-up. There are many interacting parameters including drying gas flow rate, temperature, nozzle type, design, location, & nozzle operating conditions (nozzle gas and liquid flow rate) that have a considerable impact on the product yield, residual solvent content, and the particle size and morphology. A traditional OFAT (One-factor-at-a-time), experiential, or a DOE based approach might not get an optimum due to the non-linearity and interactions between these parameters for Spray Drying and miss the detailed understanding from the mathematical model.

We have demonstrated a model-aided workflow along with the state of art process analytical characterization to optimize and transfer the process across three different Spray dryers for a sticky product. The material produced in this work has a very low Glass transition temperature resulting in yield loss due to the adhesion of the product to the wall. In this work, we model the droplet heat and mass transfer, droplet drying gas interactions, drying kinetics, and wall deposition for this sticky API. Mechanistic models (gFormulate®) and CFD models have been developed across three different equipment. gFormulate® model considers the droplet heat and mass transfer, drying kinetics, and heat loss from the wall. However, it doesn’t consider the residence time distribution of droplets, wall deposition, agglomeration, & coalescence in the Spray Dryer. gFormulate® models were used to estimate the sticky behaviour and the drying times based on the droplet size. CFD models have been developed using OpenFoam® to solve simultaneous heat and mass transfer between the droplets and the drying gas medium. CFD models were used to model the time to the wall for different droplet sizes, spray velocity, nozzle locations, distribution plate design, and drying gas velocity. Nozzle design and operating conditions have a significant impact on the process yield. The spray droplet size distribution is measured by Sympatec laser diffraction for the different nozzle designs and the operating conditions as an input to the model and experimental workflow. Mathematical models have been used to understand & optimize the impact of operating conditions on the product yield across the scale. The understanding developed using the workflow has enabled the production of API with greater than 80% yield across the scales. The advantages and limitations of the mathematical models & Spray Dryers across scales would be discussed in this presentation. Future work on the adhesion/cohesion of droplets in the Spray Dryer would be briefly discussed in this presentation.