Preparation of self-dispersible eutectic mixtures for poorly soluble drugs: Hot-melt extrusion vs. melt casting.

Solid eutectic mixtures of self-dispersible polyethylene glycol-40-stearate with fenofibrate or ibuprofen - prepared by casting or by twin-screw extrusion - were compared in terms of processability and dissolution rate at, below, and above the eutectic concentration. Furthermore, the effects of extruding with two distinct screw configurations - a shear screw and a conveyor screw - were investigated. The eutectic mixtures containing ibuprofen had a poor recrystallization tendency and therefore did not yield the desired solid state in the casting process. In contrast, they could be successfully processed by extrusion due to the initiation of recrystallization by friction and shear forces. Fenofibrate-containing solid mixtures were obtained by both methods. The extrudates of all mixtures showed a decreasing API particle size (d50 ∼ 6 to 9 µm) with increasing API concentration up to a certain threshold. For the extrudates containing ibuprofen, smaller API particle sizes were obtained with the conveyor screw; for the fenofibrate extrudates, however, the particle sizes were similar regardless of the screw configuration. Compared to the physical mixtures and the pure API, all cast samples and extrudates exhibited a considerably higher dissolution rate, depending on the excipient to API ratio. Despite the differences in particle size, similar dissolution profiles were observed for the ibuprofen extrudates produced by both conveyor and shear screws. For the fenofibrate mixtures, the dissolution profiles were similar for both screw configurations as well as for the cast references below and at the eutectic concentration. The dissolution rate was superior for the extrudates containing fenofibrate above the eutectic concentration.