BEAD MANUFACTURE BY EXTRUSION SPHERONIZATION - A STATISTICAL DESIGN FOR PROCESS OPTIMIZATION

Our recent experience in developing bead formulations for a hydrophili c drug using an extrusion/spheronization technique highlighted several critical processing factors. It was observed that the yield of beads of desired size fraction was significantly affected by water level, wa ter temperature, extrusion speed, spheronization speed, and spheroniza tion time. To further elucidate the roles of these factors, a split-pl ot factorial design was used to evaluate their effects on the yield of desired size beads, and to determine the optimal levels to maximize t he yield. Several 18 kg batches of beads were manufactured using a pre determined level of each factor. The finished beads were sieved using #14 and #20 mesh screens and the yields of beads between #14-20 mesh s creen were determined. It was observed that the temperature of water u sed at the granulation stage significantly affected the bead formation . Using room temperature water for granulation, the significant factor s were water level, extruder speed, spheronization speed, spheronizati on dwell time, and the interactions of water level with extruder speed and spheronization speed with dwell time. Whereas using 50-degrees-C water, significant factors were water level, extruder speed, spheroniz ation speed, and the interaction of water level with spheronization sp eed. The best fitting regression model describing the relationship bet ween the found yields and the factors was used to find the levels of e ach factor that would optimize the yield. Two scale-up batches at 100 kg each were manufactured using the optimal process conditions to veri fy the room temperature model. The yields from the two scale-up batche s were within 0.4% of the predicted yield using the regression model.