Monash University

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Surface modification of pharmaceutical powders

posted on 2017-02-09, 05:49 authored by Zhou, Qi
This thesis describes a body of work to investigate a mechanical dry powder coating approach aiming to modify the surface properties of fine pharmaceutical powders. Powders were coated with magnesium stearate (MgSt) in order to improve their bulk powder properties such as flowability, fluidization and aerosolization. The flow characteristics of a cohesive milled lactose monohydrate powder (Pharmatose® 450M, VMD around 20 μm) were substantially improved by processing with 1% w/w magnesium stearate using a commercially available mechanofusion system. A substantially greater improvement was demonstrated for those powders coated with 1% magnesium stearate compared to those coated with 1% fumed silica. This was attributed to the different qualities of the resulting coating of the different additive materials. The improvement of the flow of powder by mechanofusion was found to be influenced strongly by particle size distribution. Modification of the surface chemical and physical properties of such fine lactose powder (Pharmatose® 450M) via mechanical dry coating was characterized. The particle surface morphology was altered from angular to more rounded forms including an apparent modified texture after the coating process, indicating the combined effects of surface coating, morphological modification and plastic deformation. The chemical component distributions measured by time-of-flight secondary ion mass spectrometry (ToF-SIMS) demonstrated a high level coverage of near continuous coating. X-ray photoelectron spectroscopy (XPS) results supported such modification in surface chemical properties quantitatively and suggested a mean coating depth of the order of a few nano-meters. The surface energy profiles measured using inverse gas chromatography (IGC) at finite dilution indicated substantial reductions in dispersive energy for the majority of the lactose surfaces after mechanofusion, although a higher dispersive energy was demonstrated at infinite dilution. The improvement in flow behaviours for this cohesive lactose powder was strongly dependent on the surface coating quality. In this study, the changes in surface chemical properties after coating generally were shown to have a more substantial impact than the changes in surface physical properties on powder flow and cohesion characteristics. The study examined the influence of surface coating model fine lactose powders on their fluidization and de-agglomeration behaviours as well as the relationship of such powder bulk properties to the aerosol performance from an inhaler device. Improvements in powder bulk behaviour by surface modification can result in a substantially improved emitted dose as well as improved de-agglomeration performance from dry powder inhalers (DPIs). The aerosol performance of three drug powders from carrier-free DPI formulations was significantly improved after mechanofusion as measured by twin stage impinger (TSI) and laser diffraction (Spraytec). Such improvements in the aerosol performance were attributed to the reduction in agglomerate strength caused by decreasing powder intrinsic cohesion after surface modification. Intensive mechanical dry coating processing was demonstrated to be an attractive simple one-step approach to modify particle surface properties, to control powder cohesion and to obtain improved and more consistent powder bulk characteristics of fine cohesive pharmaceutical powders.


Campus location


Principal supervisor

David A. V. Morton

Additional supervisor 1

Peter J. Stewart

Additional supervisor 2

Ian Larson

Year of Award


Department, School or Centre



Doctor of Philosophy

Degree Type



Faculty of Pharmacy and Pharmaceutical Sciences