Spheronization of solid lipid extrudates: Elucidation of spheroid formation mechanism.

To explain the rounding mechanism of extrudates by spheronization method, two main concepts are found in literature: one proposed by Rowe (1985) and one proposed by Baert et al. (1993). These concepts are based on wet extrusion-spheronization method using microcrystalline cellulose as mains excipient. However, there are no concepts for the spheronization mechanism of extrudates based on solid lipids as spheronization aid. Therefore, the aim of this study is to systematically investigate the mechanism of pellet formation of lipid based extrudates by lipid spheronization method. Different lipid based extrudate formulations were spheronized and particle size distribution and shape of the pellets, at each minute of the process, were characterized. Additionally, visual investigations of the morphological alterations were performed by optical and scanning electron microscopy. Two main material temperature phases were identified as presenting important influence on the pellet formation during the process: (1) a "brittle phase", where the extrudates are broken into smaller particles and (2) a "plastic phase", where the material starts to partially melt, allowing the particles to deform. By the same token, different morphological stages, from cylindrical rods to sphere-shaped passing through a dumbbell-shaped particle, were observed and showed to be highly dependent on temperature and process time. Moreover, a new particle shape, defined as "two-spheres", was recognized and a sequential material overlapping (covering) phenomenon was identified. This particular dislocation of material, from the edges to the central region of the particles (increasing their mean diameter), was recognized at longer process times and led to the formation of a smooth surface and the final spherical shape. At the end, a new concept of pellet formation from lipid extrudates is presented considering the observed changes in the morphology and particle size of the pellets during the spheronization process.