The behaviour of the sodium salt of indomethacin in the cores of film-coated granules containing various fillers

Abstract

The aim of this study was to investigate the behaviour of sodium indomethacin trihydrate in granules made using various kinds of filler, and the effects of the fillers on the release rates of sodium indomethacin trihydrate, which is water-soluble, from uncoated and film-coated granules. The fillers used in the granules were lactose, glucose, microcrystalline cellulose, maize starch and calcium hydrogen phosphate dihydrate. The release rate from uncoated granules was very fast. Within 10 min all of the drug was released from nearly all of the granules. The effect of the porosity of the film in the coated granules was significant only when maize starch was used as filler in the cores. Release of the drug from granules containing microcrystalline cellulose, lactose or glucose as fillers was the same, regardless of the film used. Release was slightly slower from the granules containing maize starch than from the granules mentioned above. The release rate of sodium indomethacin trihydrate was markedly slower and the amounts of drug released were markedly less from granules containing calcium hydrogen phosphate dihydrate than from the other granules studied. A new component, the calcium salt of indomethacin, which is less water-soluble than the sodium salt, was probably formed in the core. Release from all of the granules studied corresponded fairly well first-order kinetics.