Solid amorphous dispersions are frequently used to improve the solubility and, thus, the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Spray-drying, a well-characterized pharmaceutical unit operation, is ideally suited to producing solid amorphous dispersions due to its rapid drying kinetics. This paper describes a novel flowchart methodology based on fundamental engineering models and state-of-the-art process characterization techniques that ensure that spray-drying process development and scale-up are efficient and require minimal time and API. This methodology offers substantive advantages over traditional process-development methods, which are often empirical and require large quantities of API and long development times. This approach is also in alignment with the current guidance on Pharmaceutical Development Q8(R1). The methodology is used from early formulation-screening activities (involving milligrams of API) through process development and scale-up for early clinical supplies (involving kilograms of API) to commercial manufacturing (involving metric tons of API). It has been used to progress numerous spray-dried dispersion formulations, increasing bioavailability of formulations at preclinical through commercial scales.

This chapter discusses amorphous dispersions manufactured using the spray drying process, which are referred to as spray‐dried dispersions (SDDs). It covers key aspects of spray drying equipment, process development, and scale‐up. The spray drying process can be broken down into the following five key steps or focus areas: spray solution preparation; atomization; drying; product collection; and secondary drying. Scalable spray drying process for SDDs is based on integrated consideration of formulation variables and process parameters that control atomization and drying thermodynamics. The chapter lists some of the key formulation selection considerations that have a significant impact on spray drying process development. The goal of scale‐up is often to ensure that the SDD particle attributes (e.g., particle size, density, physical state, and morphology) remain consistent while achieving the necessary throughput to meet clinical and/or commercial demands. This can be achieved by matching droplet size and drying rate during scale‐up.