Impact of needle-like crystals on wet and solid-lipid extrusion processes

•Needle-like drugs impair the processability of wet and solid-lipid extrusions.•More isometric drug crystals were obtained by milling.•Isometric drug crystals yielded robust and reproducible extrusion performances.

The aim of the current work was to investigate systematically the impact of needle-like drug crystals on both wet and solid-lipid extrusion processes. Co-rotating twin-screw extrusion, through 0.5, 0.7 and 1.0 mm multi-holed capillary dies, was therefore used to assess the processability of formulations containing up to 80 wt.% of three needle-like, poorly soluble active ingredients, i.e. mesalamine, nimesulide and praziquantel. Their impact on both wet and solid-lipid extrusions was evaluated prior to and after an appropriate micronisation step aimed at reducing their particle size, and obtaining more isometric particles. Occlusion of die holes and a steady increase in extrusion pressure, whose extent was found to be dependent on both the drug loading and the morphology of the drug's crystal, was observed with all the active ingredients tested. A change in particle morphology, combined to a reduction in particle size, allowed the occlusion of die holes to be considerably reduced and/or prevented, and smooth and robust extrusion processes to be achieved.

Graphical abstractA route to generate a stable extrusion processes by controlling the drug particle morphology was demonstrated.Figure optionsDownload full-size imageDownload as PowerPoint slide