Spray drying is a key process for manufacturing amorphous dispersions because of its breadth of applicability. The wide range of potential atomization techniques and controllable drying kinetics enables amorphous spray-dried dispersions (SDDs) to be produced from a wide variety of active pharmaceutical ingredients (APIs). Moreover, spray drying is a continuous, efficient, and well-characterized process that can be easily scaled up from development to pilot to production scale. The use of spray drying for pharmaceutical applications is important because amorphous dispersions are key delivery technologies for increasing the solubility of BCS Class II and IV drugs, which represent more than 50% of the compounds in pharmaceutical company pipelines.
PerformanceThe spray drying process is amenable to the manufacture of amorphous dispersions across a wide range of API physicochemical properties. Mechanistic understanding of the dissolution mechanism is critical during formulation selection. Dissolution of the primary solid dispersion particle to free drug or high-activity drug species is necessary to enchance the bioavailability of the amorphous solid.
To increase the efficiency and robustness of formulation selection, "guidance maps" are used that account for key API properties related to physical stability and performance. Drug loading and polymer selection can be efficiently optimized to achieve the desired performance attributes of the dispersion (1). The process space is then selected to provide a robust manufacturing window.
Physical stability during spray drying is maintained through the rapid drying kinetics of high-surface-area droplets. Rapid quenching of droplets to achieve a low mobility state, facilitated by use of a high-Tg polymer, is critical to achieving an amorphous dispersion. Atomization and drying conditions are both optimized to ensure a reproducible, robust process that achieves a molecular dispersion and promotes physical stability during in-process hold times.