Investigation into the manufacture and properties of inhalable high dose dry powders produced by co-milling API and lactose with magnesium stearate

The aim of the study was to understand the impact of different concentrations of the additive material, magnesium stearate (MGST), and the active pharmaceutical ingredient (API), respectively, on the physico-chemical properties and aerosol performance of co-milled formulations for high dose delivery. Initially, blends of API- Lactose with different concentrations of MGST (1 - 7.5% w/w) were prepared and co- milled by the jet-mill apparatus. The optimal concentration of MGST in co-milled formulations was investigated, specifically for agglomerate structure and strength, particle size, uniformity of content, surface coverage and aerosol performance. Secondly, co-milled formulations with different API (1 - 40% w/w) concentrations were prepared and similarly analyzed. Co-milled 5% MGST (w/w) formulation resulted in a significant improvement in in-vitro aerosol performance due to the reduction in agglomerate size and strength compared to the formulation co-milled without MGST. Higher concentrations of MGST (7.5% w/w) led to reduction in aerosol performance likely due to excessive surface coverage of the micronized particles by MGST, which led to failure in uniformity of content and an increase in agglomerate strength and size. Generally, co-milled formulations with higher concentrations of API increased the agglomerate strength and size, which subsequently caused a reduction in aerosol performance. High dose delivery was achieved at API concentration of > 20% (w/w). The study provided a platform for the investigation of aerosol performance and physico-chemical properties of other API and additive materials in co-milled formulations for the emerging field of high dose delivery by dry powder inhalation.