It has been shown previously that solid lipid extrusion with several drugs is uncomplicated and robust. In this work it has been shown for the first time that needle shaped drugs cause problems during solid lipid extrusion and sometimes such drugs cannot be processed. Extrusion performance could not be improved by i: changing the screw configuration or the die geometry by increasing the die diameter, ii: changing the type of lipid or iii: additives or iv: decreasing the drug load. In contrast milling the needle-shaped crystals before extrusion in order to obtain more isometric particles led to smooth reproducible processes. Praziquantel, mesalazine and caffeine were milled. Then both milled and unmilled powders were extruded using the same excipients and process parameters. The processing performance was compared, the surface texture of the extrudates was analysed and the drug crystals were investigated regarding their particle size and shape before and after milling and extrusion, respectively. The effect of milling on the process was significant for praziquantel and caffeine, whereas needle-shaped mesalazine crystals were broken down during extrusion and caused less problems during the process. (C) 2010 Elsevier B.V. All rights reserved.