Model Assisted Development of an Amorphous Solid Dispersion Formulation in a Dry Granulated and Film Coated Tablet Considering Dissolution As the Process and Material-Dependent Response

This work describes the modeling approach followed in the development of the manufacturing process of a solid oral dosage form for an amorphous solid dispersion formulation using dry granulation. Bench scale work was essential to generating target values for intermediate material properties that ensured acceptable product performance. These targets were used as a criterion for the design exercise performed using an empirical model with historical data that was leveraged to scale up the process without any experimentation on the intended commercial scale. Following this first campaign, new sets of conditions were designed using a physics-informed model to guide the experimental work. A hybrid model was built for the entire manufacturing train considering all of the dependencies across materials and processes including the kinetics of the changes in tablet dissolution that were attributed to the exposure of the core tablet to temperature and humidity. The model was used in finding feasible operational ranges across unit operations, accounting for operational constraints and expected variations in the incoming materials.