Visualization and Process Understanding of Material Behavior in the Extrusion Barrel during a Hot-Melt Extrusion Process Using Raman Spectroscopy

The aim of this research was to improve understanding of material behavior in pharmaceutical hot-melt extrusion by implementing a Raman probe in each section of the barrel. Fourier-transform infrared spectroscopy measurements were performed to confirm the Raman observations. Metoprolol tartrate (MPT) concentration (10 and 40% in Eudragit RSPO), extrusion temperature (100, 120, and 140 °C), and screw speed (80 and 160 rpm) were varied to examine their influence on polymer–drug solid state throughout the barrel. When extruding a formulation with a 40% MPT concentration, the broadening of MPT peaks indicates melting of MPT between sections 2 and 3, caused by the first kneading zone. Decreasing the concentration to 10% shows an additional spectral difference (i.e., peak shifts indicating interactions between MPT and the carrier) between sections 5 and 6, due to formation of a solid solution. At a 10% MPT load, increasing the extrusion temperature does not influence the solid state or the barrel section where the final solid state is obtained. At a drug load of 40%, the solid state of the end product is reached further down the barrel when the temperature decreases. Doubling the screw speed when processing a 10% MPT formulation does not affect the solid state of the product or the location where it is obtained. In contrast, at a 40% drug load, the section where the final product is produced, is situated earlier in the barrel, when applying a higher speed. The Raman spectra provide real-time information about polymer–drug behavior throughout the barrel, facilitating process understanding and optimization.