Moving from low shear to high shear blending: a predictable scale-up or a source of uncertainty?

Authors: , , ,

Dry powder inhalation formulations include an excipient and an active pharmaceutical ingredient (API) which are present in different proportions and must be homogeneously blended. There are mainly two kinds of mixers available in the market to perform this operation: low-shear and high-shear mixers. The predominant mechanisms of both types of equipment are different and may impact the final mixture in terms of: (i) quality of mixing, (ii) aerodynamic performance and (iii) formulation stability. This work intends to compare the first two attributes stated above when using both types of blenders. For this purpose, six blends were produced in Turbula® (low-shear) and in Diosna® (high-shear) units and were evaluated for blend homogeneity and aerodynamic performance.
The obtained results show that even though the blend uniformity was very similar for both processes, the quality of mixing given by the mixing index (MI) is higher for blends processed in the high-shear unit. Additionally, increasing mixing time and velocity did not have an impact on the quality of mixing, within the ranges explored in this work. Regarding aerodynamic performance, a decrease of the emitted dose (ED) and the fine particle dose (FPD) was observed for high-shear blends. Additional mixing steps on the high-shear blends proved to have an impact on the aerodynamic performance, since the optimum mixing time appears to have been achieved in the first additional step, after which a re-segregation may have occurred, with a detrimental impact on the in-vitro deposition profile. When moving from low-shear into high-shear blending, the observations drawn from this work should, therefore, be taken into consideration.