The behaviour of various fillers in spheronized uncoated and film-coated granules containing slightly water-soluble indomethacin

Abstract

The release of indomethacin from uncoated and film-coated spheronized granules was investigated. Granules containing indomethacin and various fillers were spheronized using a Calevaspheronizer. The characteristics of the granules and the release of indomethacin from them were examined. The fillers used in the granules were microcrystalline cellulose, lactose, glucose, calcium hydrogen phosphate dihydrate and maize starch. Marked differences were observed in spheronizing ability between the various fillers. It was most difficult to obtain perfect spheres with the crystalline fillers glucose and lactose. Spheronizing was best for granules containing maize starch or microcrystalline cellulose. Release from uncoated granules was very fast. In 10 min nearly 100% of the drug was released, whatever filler was used. The Spheronization process only affected drug release from granules containing microcrystalline cellulose as filler. It changed the apparent densities of granules only in the case of those containing glucose. The ethyl cellulose: hydroxypropylmethyl cellulose ratio affected the release rate of indomethacin from all granules film-coated using a fluidized-bed technique irrespective of the filler. As the permeabilities of the film fell the release rates also decreased. Spheronization of the core resulted in release rates of indomethacin differing from those in earlier studies on the release of indomethacin from unspheronized granules. Release of the drug was slowest from granules containing microcrystalline cellulose (some 30% in 8 h).