Use of extrusion-spheronization to develop an improved oral dosage form of indomethacin

Two new pelletized formulations of indomethacin were developed and compared against pellets from the proprietary product, Indocid-R. Extensive dissolution testing involving pH-shift and topographical profiling showed that the new product containing polyvinylpyrrolidone had slightly faster in vitro release than the commercial product, but surprisingly the other new product containing sodium lauryl sulphate had reduced drug release. The cause of the anomalous result was shown by solubility studies and scanning electron microscopy to be related to the ability of the wetting agent to promote fragmentation of the microcrystalline cellulose used as spheronization aid into small crystallites, retarding drug release. The two new products had improved sphericity compared to the proprietary product when examined by image analysis. However, on in vivo testing in dogs, the new product containing sodium lauryl sulphate had the highest bioavailability of the three preparations examined due to its effect as a penetration enhancer. (C) 1997 Elsevier Science B.V.