PREPARATION OF SPHERICAL BEADS WITHOUT ANY USE OF SOLVENTS BY A NOVELTUMBLING MELT GRANULATION (TMG) METHOD

A new method, the tumbling melt granulation (TMG) method, for preparin g spherical beads without any use of solvents, was developed. A powder ed mixture of meltable materials and non-meltable materials was fed gr adually and successively onto the seed materials, which were blown wit h hot slit air using a centrifugal fluidizing bed granulator. As a con sequence, the mixture adhered to the seed materials to spontaneously f orm the spherical beads. First, the effects of several factors concern ed with granulatability were investigated using nonpareil as the seed materials; lactose as the non-meltable material; and polyethylene glyc ol, hydrogenated rape oil, and fatty acids as meltable material. In or der to prepare spherical beads with a narrow particle size distributio n and a smooth surface, it was concluded from this series of experimen ts that the bed temperature during the processing should be maintained at least 5 degrees C higher than the melting point of the meltable ma terial; particle sizes of both the meltable and the non-meltable mater ials should be lowered below one-sixth of the diameter of the seed mat erials; and the mixing ratio of the meltable material in the powdered mixture should be set at an optimum value. Then, the TMG method was ap plied to several kinds of drugs with various physicochemical propertie s. It was revealed that this method was very useful and widely applica ble since even bisbentiamine, with which it was difficult to prepare s pherical beads by the wet powder coating method, could be granulated e asily by this new method. Further, it was shown that this method could be applied successfully to seed materials whose shape was non-spheric al, such as cube-shaped sucrose crystals.