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.
Figure 1: Spray drying process and key amorphous dispersion attributes.
|
Bend Research, a leader in the production of amorphous dispersions for pharmaceutical applications, has devoted a substantial
amount of work to the application of fundamental engineering principles to the spray drying of amorphous dispersions. Application
of fundamental knowledge has made it possible to obtain spray-dried amorphous dispersions with the desired stability and performance
attributes, smooth process scale-up, and downstream manufacturability. An overview of the process and product is shown in
Figure 1.
Performance
The 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.
Stability
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.
