Effect of batch size on the granule properties in planetary centrifugal granulation.

Abstract

A granulation method using a planetary centrifugal mixer, called planetary centrifugal granulation, has been developed for small-scale production, such as extemporaneous preparation in pharmacies. Although the impact of its operational parameters on granulation is described, the scale effect has not been investigated. Therefore, we aimed to reveal the effects of vessel size and vessel filling rate on granule properties. In this study, ibuprofen 20% granules consisting of lactose, cornstarch, sodium carmellose, and talc were used as model granules. Granulation was performed using geometrically similar containers, 6-58 mL, with a filling rate of 20-70%. After granulation, we monitored the granule properties, for example, median diameter (d50), span of particle size distribution, and sphericity. At filling rates of 40% and 50% in the 58-mL vessel, the granules grew larger in diameter, and at a rate of 30%, the granules showed a higher sphericity. When the filling rate was 30%, d50 became larger and the span decreased as the vessel size increased. The yields of the granules were higher than 95% when using the 12-58 mL vessel. Lastly, the drug content uniformity and drug dissolution behavior of the granules produced in different vessel size were examined. The granules showed similar drug consistencies and drug dissolution profiles. In conclusion, the quality of the products was not affected by changes in vessel size. Thus, pharmacists could prepare and compound the granule formulations with high yield and appropriate quality using an adequate vessel in the same manner.