THE INFLUENCE OF 4 SELECTED PROCESSING AND FORMULATION FACTORS ON THE PRODUCTION OF SPHERES BY EXTRUSION AND SPHERONIZATION

A factorial designed experiment has been used to investigate the effect of formulation and extrudate production variables on the properties of spheroids produced by extrusion and spheronisation. The variables were the Avicel and water content of the formulation (which also contained lactose, and indomethacin as a model drug), extrusion speed and die length. The effects that were investigated were the force required for steady-state extrusion (ram extruder), the shape and size distribution of the spheroids, and the drug release profile from the products. The most important variable was found to be the water content, in particular the water content at the die wall during extrusion (and presumably at the surface during subsequent spheronisation) was found to be important. Factors which may be expected to decrease water availability at the die wall (decreased water and Avicel contents, increased extrusion speed and die length) were found to have detrimental effects on the product (in terms of size distribution and shape). All the variables had some effect on the dissolution performance of the spheroids, but those due to die length and extrusion speed were only significant when the Avicel content was low and the water content high.