Optimization of size distribution of granules for tablet compression

Abstract

Particle size distribution of granules for tablet compression manufactured by a high-shear-mixer were examined, and the relationship between this size distribution and physical properties (e.g., angle of repose, angle of spatula, loose hulk density, tapped bulk density, compressibility, hardness of tablets and weight variation of tablets) was determined. Optimization of particle size distribution was also carried out, taking the effects of hardness and weight variation into consideration. The particle size distribution of granules for tablet compression could be expressed as a function of median particle size and standard deviation with a logarithmic normal distribution. The physical properties of granules for tablet compression and tablets were significantly affected by this factor. A contour diagram of the hardness of the tablets compressed with an autograph was consistent with that of compressibility. The contour diagram of the hardness of tablets compressed with a rotary tableting machine was different, however, and was found to be affected by both the fluidity of granules for tablet compression and compression speed. Furthermore, tablet hardness increased as the median particle size decreased, when the standard deviation was less than 1.0. The physical properties of tablets could be predicted from the contour diagram of optimum particle size distribution of granules for tablet compression. As a result, the time spent making the tablet formulation could be reduced. It was found that the optimum ranges of median particle size and standard deviation were less than 150 μm and less than 1.0, respectively.