Hot melt coating technology: influence of Compritol 888 Ato and granule size on chloroquine release

The tangential spray technique was used to coat chloroquine granules with Compritol 888 Ato in a fluidized bed (Glatt GPCG-1,1). After validation of the assay method for chloroquine, dissolution tests were carried out on four size fractions obtained from the same batch of granules. The dissolution profiles obtained showed differences in the rate of release between one fraction and another, despite the fact that each of these fractions had been coated with the same quantity of wax. This suggests that the rate of release of the chloroquine may be adjusted by controlling the size of the granules. Furthermore these dissolution profiles were characterized by a rapid release phase followed by a slow release phase. Examination of the surfaces of the granules from the various size fractions under a scanning electron microscope revealed that Compritol did not form a continuous film but existed rather as a lipid environment around the granule. This lipid environment was made up of solidified droplets of the wax which had become piled up on the surface of the granule. Compression of the granules produced tablets which remained intact until chloroquine dissolution was complete. This undicated that the active substance diffused across the Compritol matrix generated during compression. Determination of the dissolution kinetics using the Higuchi model demonstrated the diffusion release mechanism.