The aerosol performance and physico-chemical properties of co-milled dry powder formulations for high dose delivery

Abstract

The overall aim of the thesis was to investigate the aerosol performance and physico-chemical properties of dry powder formulations produced by co-milling an Active Pharmaceutical Ingredient (API- Beclomethasone Dipropionate - BDP) with an additive (Magnesium Stearate - MGST), using the jet mill apparatus, for high dose delivery. Co-milled formulations were produced at the set concentration of 1% w/w BDP, varying concentrations of MGST (0%-7.5% w/w), adding lactose as the final bulking agent. In general, 5% w/w MGST was found to be the optimal concentration for aerosol performance in terms of powder dispersibility% and emitted dose (ED%) from in-vitro aerosol performance analysis. The effect of BDP concentrations (from 1% w/w-40% w/w) co-milled at a fixed concentration of 5% w/w MGST, was investigated and a reduction in aerosol performance was observed with an increase in BDP% w/w concentration. High dose delivery (in mg of API) was achieved at a BDP concentration of < 20% w/w. In the final experiment, the effect of relative humidity (RH-between 50-75% RH) after short term storage (0, 1, 5, 15 days, respectively) on the aerosol performance and physico-chemical properties of the co-milled formulations (1% BDP/99% lactose and 1% BDP/5% MGST/94% lactose) was investigated. Generally, aerosol performance was significantly (p<0.05) higher in the co-milled formulation containing 5% w/w MGST, after storage at 75% RH for 15 days. This was likely due to the hydrophobicity of MGST which provided a barrier from moisture absorption on the surface of micronised particles. The results from this thesis demonstrated how high dose delivery (in mg) with improved powder stability can be achieved by co-milling of BDP with the additive material MGST.