Hot-melt Extrusion

Hot-melt extrusion (HME) is the processing of polymeric materials above their glass transition temperature (T_g) to effect molecular level mixing of thermoplastic binders and/or polymers with active compounds. Used in several industries, HME uses a combination of thermal and mechanical energy to improve continuous processing for reproducible processing of materials, along with dust and solvent reduction and online monitoring.

In pharmaceutical manufacturing, HME is used to disperse APIs in a matrix at the molecular level, thus forming solid solutions. This enables drug delivery systems for poorly soluble drugs or specialized drug forms such as films for transdermal patches.

The choice of an adequate polymer as a matrix to form stable solid solutions is crucial in HME. Polymers with a high solubilization capacity are particularly suitable because they can dissolve large quantities of drugs. Polymers for hot-melt extrusion experiments are based on different monomers and chemical structures, such as homopolymers, copolymers, amphiphilic copolymers as well as solubilizers and plasticizers. Consideration for each material must take into accountconsider the polymer's solubility in a solvent, which can vary from high lipophilicity to high hydrophilicity.

Polymers for hot-melt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature. In developing a HME drug system, the glass transition and melting temperatures are critical factors. The extrudability of a polymer is mainly determined by T_g or T_m and melt viscosity. Most polymers demonstrate thixotropic behavior where the viscosity reduces as a function of increasing shear stress.

In the hot-melt extrusion process, the API and the excipients are fed into the extruder. All components are sheared, heated, plastified, mixed and dispersed, and finally shaped by pressing them through a die opening. Developing a HME-based manufacturing project requires control of several processing parameters that affect final product quality: Residence time distribution and specific mechanical energy consumption (SMEC) must be considered, and also the temperature of the melt at the extruder die, the pressure at the die, and screw torque.

Identify drug candidates at lab scale

Thermo Scientific twin-screw extruders are built with similar geometries across their different sizes. This enables experimentation and feasibility projects developed with a lab-scale (11 mm screw) instrument to be scaled-up to commercial size using a scientific approach. Using a lab-scale extruder minimizes the use of expensive APIs and enables fast and easy clean-up between experiments.

Formulation development platform

Designed to fit between the development lab and production line, the modular Thermo Scientific Pharma 16 Twin-Screw Extruder can manage several drug formulation projects, including controlled release formulations, solubility enhancement, co-extrusion and implants, abuse deterrent formulations, and wet and melt granulation projects. A modular design enables formulation scientists to switch from hot-melt extrusion and continuous granulation projects without engineering the extruder system.

Production-scale HME

For consistent, controllable processing of hot-melt drug formulations that are suitable for utilizing PAT, the Thermo Scientific Pharma 24 Twin-screw Extruder promises reduced product changeover time and minimized scale-up risk, while allowing for fast and easy cleaning.

This platform includes integrated ancillary equipment for both project development and commercial production including pre-mixers, feeders, chill rolls, air-cooled conveyors, pelletizers, and sheet or blown film lines. GMP standard pharmaceutical versions of the ancillaries are available with stainless steel construction and dust-tight touch-screen operator interface.