Use of canonical and other analyses for the optimization of an extrusion-spheronization process for indomethacin

Preliminary experiments with indomethacin 40%, microcrystalline cellulose 20% and lactose 40% wetted with optimum water content, produced pellets in low yield and with poor sphericity, using an extrusion-spheronization process. The difficulty in processing the drug was overcome principally by modifying the formulation to include a newly developed spheronization aid composed of one part hydrophilic polymer coprocessed with 19 parts microcrystalline cellulose by spray-drying. Alternatively addition of 0.5% polyvinylpyrrolidone and 1.25% sodium lauryl sulphate was helpful. When processed under optimum water content and experimental conditions, developed using factorially designed experiment, products with variable dissolution profile and superior sphericity to the proprietary pelletized product, Indocid-R, were produced in high yield. The use of canonical analysis to aid interpretation of experimental results is described. (C) 1997 Elsevier Science B.V.