Explanation of Process

Recent advances in drug discovery have led to an increase in the number of active pharmaceutical ingredients (APIs) that are poorly water soluble (PWS). These PWS drugs cannot be formulated using traditional methods. Hot melt extrusion is emerging as a leading technology for increasing drug solubility and enhancing bioavailability.

Foster Delivery Science’s pharmaceutical hot melt extrusion is performed in a cGMP production facility using single and twin screw extruders qualified and designed for drug delivery applications. Our equipment and extruders allow us to work with as little as 3-10 gram batches of material for proof of concept and early formulation development. We can scale to a 27mm twin screw extruder for clinical trials and commercial manufacture.

Our single and twin screw extruders can be configured for a variety of processing approaches including tandem extrusion and coextrusion. Twin screw extruders are frequently used to prepare solid dispersions due to their high kneading and dispersing capacities, and short transit time. Screw design, screw rotation and screw speeds can be custom tailored for each formulation. Our feeders are designed to accurately dispense APIs, excipients and polymers in a wide range of forms, including powders, liquids or pellets. The twin screw hot melt extrusion process is self-wiping. Material is transferred from one screw element to the next, with mixing and pumping resulting in a combination of shear forces (compression and expansion) between the screw and barrel wall. Melt energy is derived from the input temperatures, the shear forces and the mechanical energy from the shafts.

Each formulation produced by hot melt extrusion has a “process energy”. Process energy is comprised of mechanical and thermal energies that ensure homogenous mixing without degradation of the API or excipients.

Mechanical energy influences the degree of mixing achieved in the process. Thermal energy determines the amount of heat the formulation experiences in the process. A number of variables are used to optimize the process formulation, including but not limited to barrel and screw designs. Extruder barrels are zoned in sections which are individually heated and cooled depending on the formulation process parameters. Extruder screws are individually constructed with components that assist in melting (via shear forces) and convey material through the barrel, while mixing and homogenizing the formulation.

To facilitate in process formulation development, our engineers characterize each formulation for thermodynamic and rheological properties. This data is for initial computer simulation of screw and barrel designs, and initial process conditions.

Initial processes are evaluated, optimized and scaled on one of several extruders in our development lab or cGMP suites.