A FACTORIAL APPROACH TO HIGH-DOSE PRODUCT DEVELOPMENT BY AN EXTRUSION SPHERONIZATION PROCESS

Extrusion/spheronization technology has been used for preparing high drug-loaded pellets. Typical formulations include 40-60% microcrystalline cellulose (MCC) to impart the plastic characteristics required for this process. Studies have suggested that pellets containing greater than 80% drug are difficult to process and require special grades of MCC. Most of these studies focused on either the process or formulation aspects of the product and failed to explore the interactions of process and product. Statistical experimental designs are well suited for exploring both process and product variables and their interactions with each other. This study addresses pelletization of a high dose drug with low density. A Nica(R) radial (basket-type) extruder was used in extrudate preparation, followed by spheronization on a serrated plate spheronizer. A Plackett-Burman screening design was employed to investigate product and process parameters affecting final pellet drug content, density and roundness. MCC type and concentration, water concentration, spheronizer speed and residence time and extruder screen size were found to be statistically significant in imparting desirable attributes to the final product. Wet mixing time, extruder feed rate and extrusion rate did not significantly affect pellet properties.