Dispersion state analysis in hot melt extruded, highly drug-loaded 3D printing filaments applying Raman-microscopy

Highly drug-loaded polymer formulations are favorable intermediates in pharmaceutical applications for example for the individualized production of medicines via 3D printing with the maximum flexibility regarding dose strength and drug combination in a single dosage form. However, high disperse drug loads are challenging for the process itself and the (intermediate) product properties, making the knowledge about the dispersion state of the drug particles achieved by the production process helpful to overcome such challenges. Therefore, a novel dispersion state analysis technique based on scanning Raman microscopy is proposed in the present study and applied to HPMC filaments loaded with 20 wt.%, 40 wt.% and 60 wt.% theophylline. The qualitative and quantitative evaluations of the scans were correlated to melt viscosities, process data and mechanical properties of the filaments. The analyses revealed not only an increasing particle size reduction with increasing drug load and thus increasing viscosity and mechanical energy input. The particle size reduction also caused a change of the filaments’ mechanical properties from elastic ductile to rigid brittle. Furthermore, an alignment of the elongate drug particles with the frozen three-dimensional flow pattern of the extruder and not only with the extrusion direction was elucidated. Therefore, the necessity to investigate the dispersion state further is highlighted for future studies on highly drug-loaded polymer formulations, providing a novel measuring technique applicable for challenging pharmaceutical formulations.