Pharma Production: An Overview of Downstream Pharmaceutical Processes

When developing new drugs, it’s often best to integrate a cooling roller early in research, as using a chill roll from the outset can simplify scale-up. Its influence on the final product is particularly significant for amorphous solid dispersions (ASDs).

The chill roll is typically used in higher-throughput setups or to simplify milling steps—for example, during production of oral solid dosage forms.

Recent studies show that chill roll processing, which produces easily milled flakes, is superior to pelletizing the extrudate.

Producing consistent flakes with the chill roll is straightforward. The melt flows from the extruder die onto two cooled rolls set at a defined gap and speed. The rolls’ cooling rate is controlled by a thermostatic bath. Counterrotation forms a thin film and cools it, which is then peeled off, further cooled on a conveyor, and crushed into flakes by a rotating flaker. Flake size can be varied by adjusting the roll gap or flaker speed.

The chill roll’s main advantage is its precise, well-controlled cooling—essential for forming stable amorphous dispersions.

Other considerations come into play when cutting an extruded strand. The strand must not be so brittle that it breaks as it’s pulled for cutting, but not so elastic that it jumps or pops out of the pelletizer. Achieving the right strand behavior is essential for effective drug development and preparation.

In pelletizing, cooling of the extrudate is not required. The cutting knife sits immediately adjacent to the die, producing homogeneous pellets. Multiple die outlets allow higher throughput. Pellets are guided into a cyclone and can be shaped with rounded ends or edges. The face-cut and cyclone process generates more rounded pellets, while an accessory such as the Varicut Pelletizer—designed like a rotating knife—cuts extruded strands into cylindrical pellets of 1 to 3 mm in length.

For best results, use a highly filled, non-sticky product with 20–50% solid content in the melt. This allows shear stabilization and easy, consistent cutting.

Printing precision depends on the consistency of the filament diameter, which can be monitored with a laser gauge to ensure uniformity. To improve efficiency and product quality, it is essential to minimize pressure pulsation during extrusion, as fluctuations can affect filament diameter.

Using the same sheet-die setup and an appropriate formulation, the system can also produce adhesive patches. These patches deliver a controlled API dose through the skin into the bloodstream. HME is compatible with several patch types, such as single-layer systems where drug and adhesive are combined and extruded as a strand applied onto a carrier film.

This fast, cost-effective process supports production from various materials, including melt, pellets, or powders. Compared to other downstream equipment, injection molding yields products with high density, making it better suited for sustained-release formulations or implant applications rather than fast-release products.

The final product’s diameter depends on the die geometry, while its length is determined by the cutting frequency—both of which can be easily adjusted. This flexibility allows for efficient development and reproducible results across various dosage forms.