Further observation of content uniformity of d-alpha-tocopheryl acetate as an oily drug in granules obtained by wet granulation with a high-shear mixer.

Using d-alpha-tocopheryl acetate (VE) as a model drug, we investigated the effects of the amount of binder solution on content uniformity of oily drugs in granules obtained by, wet granulation with a high-shear mixer. When the amount of binder solution was below the water volume for the plastic limit, the content of VE was less than 50% in the fractionated fine granules, but was more than 200% in the fractionated large granules. Large variations were seen in the contents of VE even if the granulation time was extended up to 30 min. This large variation was not decreased by the milling process. On the other hand, when the amount of binder solution was at or above the water volume for the plastic limit, less variation was observed in the content of VE throughout the granules, and the content of VE was fairly uniform. Nuclei rich in VE were formed when VE was adsorbed with the powder before granulation. When the amount of binder solution was below the water volume for the plastic limit, the shearing force of mixer blades to the granules was low, so that the nuclei rich in VE were not fragmented. This led to the nonuniformity of VE content throughout the granules. On the other hand, when amount of binder solution was at or above the water volume for the plastic limit, the shearing force of mixer blades against the granules increased and became sufficient to fragment the nuclei. This led to the uniformity of VE content throughout the granules. This study showed that content uniformity of VE in the granules can be achieved by controlling the physical shearing force of mixer blades by regulating the amount of binder solution.