Carrier based formulations (also called ordered mixtures) were produced with lactose carrier and four different micronized APIs: budesonide, beclomethasone dipropionate, carbamazepine polymorph 1 and salicylic acid, using two different micro-mixing methods; hand-shaking and tumbling blending. The formulations were assessed for homogeneity and for fine particle fraction (FPF) using a simple passive prototype device, the “screenhaler”, in combination with the Next Generation Impactor, NGI. Pure APIs were investigated for primary particle size and also for fine particle fraction using a set up with the Turbuhaler® mouthpiece and the NGI.
FPF values obtained were in the range 7 – 24% for the ordered mixtures and 20 – 46% for pure APIs. Homogeneity results, expressed as RSD of API content, ranged from 0.5 to 16%. Unexpectedly, a clear correlation was observed between the fine particle fraction of the pure micronized API and formulation homogeneity, valid for both mixing methods. The correlation can be explained by the influence of shear forces, being a dominating mechanism in the mixing processes as well as in the fine particle test with the Turbuhaler mouthpiece. Surprisingly, no correlation was found between the FPF of pure API and the FPF of the corresponding formulation assessed in the “screenhaler” device. This lack of correlation is believed to be due to the fact that different dispersion mechanisms are acting in the two tests, with high shear forces present in the former but not in the latter.