Low-Temperature Hot Melt Extrusion: Solid-State Organization and Mechanical Performance of Lipid Filaments

The bioavailability of highly lipophilic, poorly soluble drugs can be improved effectively, when formulated in lipid-based systems. Solid lipids generally offer greater physical robustness than liquid lipids but slower release. Hot-melt extrusion (HME) and additive manufacturing (AM) enable personalized release by tailoring composition and geometry. However, the limited availability of suitable solid lipid-based materials, particularly for processing thermolabile and lipophilic drugs, restricts their application. Polyglycerol esters of fatty acids (PGFAs) represent a promising class of lipids due to their stable α-form, tunable hydrophilicity, and printability. Nevertheless, the interplay between lipid processing, solid state, and rheological behavior remains insufficiently understood for HME and AM. In this study, felodipine (Biopharmaceutics Classification System (BCS) class II drug) was incorporated into a PGFA matrix to obtain a fully dissolved system at the minimum processing temperature. Drug loading induced melting point depression, delayed crystallization, and introduced disorder in crystal packing, thereby weakening the crystal network and enhancing filament flexibility, enabling printability. Printable filaments were achieved at 95 °C, while an undetectable crystalline drug was observed at 120 °C. This work demonstrates that drug-lipid interactions can be employed to enhance processability: while low-temperature processing of PGFA was feasible, drug modifications into the lipid solid state impacted the rheological and mechanical properties essential for additive manufacturing. Beyond this specific system, this study provides a rational proof of concept for processing solid and liquid lipids via continuous melt-based technologies.