The possibility of achieving an interactive mixture with high dose homogeneity containing an extremely low proportion of a micronised drug.

The homogeneity of binary mixtures containing coarse particulate mannitol and three different size fractions of sodium salicylate particles was investigated. The proportion of sodium salicylate (0.15% w/w and 0.015% w/w) and the sample size of the mixture were also varied. The homogeneity of these experimental mixtures was compared with the theoretical values that would be expected from ordered, adhesive interactive (pseudo-random) and random model mixtures. The results indicated that adhesive interactive forces were created between the drug and the carrier particles in most of the experimental mixtures, since their homogeneity tended to be higher than that of a theoretical randomised mixture. In fact, there was some resemblance to an ideal ordered state in mixtures containing the highest drug proportion (0.15%) and the smallest particles. However, the effect of sample size was not negligible and it was concluded that the number of drug particles interacting with individual carrier particles was not constant but was in fact related to a process of randomisation. The homogeneity of the mixture was predicted using two approaches: the ratio of the number of drug to carrier particles in the mixture and the absolute number of drug particles, estimated by weight, in the sample. It is suggested that calculating the relative numbers of particles by weight in the mixture could aid in predicting the feasibility of achieving an interactive powder mixture with a high dose-homogeneity.