The impact of material attributes and process parameters on the micronisation of lactose monohydrate.

Dry powder inhalers (DPIs), which are important medicines for drug delivery to the lungs, require drug particles in the respirable size range of 1-6 μm for optimal lung deposition. Drugs administered by the oral route also derive benefit from particles in this size range owing to their large surface area to volume ratio, which provides potential for rapid dissolution. Micronisation used in the production of particles, however often leads to heterogeneous product containing mechanically activated surfaces with amorphous content. This study was therefore carried out to evaluate the effect of particle properties of three grades of lactose monohydrate, with sizes above and below the brittle-ductile transition (dcrit) and their interaction with process variables on the quality of micronised material. Following an experimental design, the impact of three factors (grinding pressure, injector pressure and feed rate) on the particulate attributes of micronised powders produced from the different size grades was assessed. Processing conditions were shown to be important determinants of powder properties only for the coarsest starting material. Ultrafine material was achieved by processing finer grade feed stock below dcrit. However the resultant product was more crystalline and transformed on heating to the anhydrous state with markedly reduced onset temperature with lower energy surfaces than powders produced from larger sized starting material. Thus the propensity for micronisation of lactose monohydrate can be altered through control of starting materials and optimal settings for process variables.