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 a nd three different size fractions of sodium salicylate particles was invest igated. 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 e xperimental mixtures was compared with the theoretical values that would be expected from ordered, adhesive interactive (pseudo-random) and random mod el mixtures. The results indicated that adhesive interactive forces were cr eated between the drug and the carrier particles in most of the experimenta l mixtures, since their homogeneity tended to be higher than that of a theo retical randomised mixture. in fact, there was some resemblance to an ideal ordered state in mixtures containing the highest drug proportion (0.15%) a nd the smallest particles. However, the effect of sample size was not negli gible and it was concluded that the number of drug particles interacting wi th individual carrier particles was not constant but was in fact related to a process of randomisation. The homogeneity of the mixture was predicted u sing two approaches: the ratio of the number of drug to carrier particles i n the mixture and the absolute number of drug particles, estimated by weigh t, 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. (C ) 2001 Elsevier Science B.V. All rights reserved.