Spheronization of solid self-dispersible eutectic extrudates: A small-scale feasibility study.

Recently, twin-screw extrusion has been identified to be a superior process for producing solid self-dispersible eutectics from polyethylene glycol-40-stearate and fenofibrate or ibuprofen compared to a simple casting method. Thus, for the development of lipid pellets as carriers for poorly soluble active pharmaceutical ingredients (APIs) and as fillings for patient-individualized capsules, the extrusion/spheronization process appears to be a promising method. However, due to their eutectic nature, the extrudates exhibit low and variable melting ranges depending on their composition, making them challenging to spheronize. The feasibility of extrusion/spheronization of extrudates from polyethylene glycol-40-stearate and fenofibrate or ibuprofen was investigated at concentrations below, at and above their respective eutectic concentration on a small scale (10 and 20 g batches), using a customized cutting tool and spheronizer. The study focused on the mechanical properties of the various extrudates and their effect on the spheronization process, as well as the impact of the spheronization process on the API particle size within the extrudates. Spheronization on a small scale was possible for all extrudates without API, those containing ibuprofen or containing fenofibrate below the eutectic concentration, respectively. However, to prevent the extrudates from sticking to the spheronizer jacket, the process temperature needed to be lowered as the API concentration increased. Furthermore, the rounding of the extrudates without API or containing fenofibrate was less effective compared to the extrudates containing ibuprofen, due to slight differences in resilience and considerable differences in hardness of the extrudates at the respective spheronization temperatures. The size of the API particles within the extrudates (d50 6 to 9 µm) decreased by 1 to 3 µm (d50) during the spheronization process for most formulations.