MIXING OF PHARMACEUTICAL SOLIDS .1. EFFECT OF PARTICLE-SIZE ON MIXING IN CYLINDRICAL SHEAR AND V-SHAPED TUMBLING MIXERS

The mixing of a cohesive drug with a cohesive, non-cohesive and free-flowing excipient was studied using two types of mixers, cylindrical shear and V-shaped tumbling. Two mixing indices, one based on complete random mixing, s/σR, and the other based on standard specifications, s/σA, were used to evaluate the data. Both indices gave similar results for mixing cohesive drug with a free-flowing or non-cohesive excipient and were suitable for evaluating homogeneity. However, for mixing a cohesive drug with a cohesive excipient, s/σR was not a suitable index, while s/σA could be used. The 'mixing margin', a concept proposed by Hersey [3], is not a very useful tool in assessing mix-ability of powders having too large or too small particle size distributions. Because of electrostatic charging, preferential sticking of the drug to the walls of the mixer resulted in a lower mean value of the drug in the mixture. Although the mixing indices suggested that the desired mixedness was reached, it is proposed that the mean percent of the active ingredient should be checked in addition to the mixing indices for ensuring the uniformity and potency of the drug content in solid state mixtures. © 1979.