Investigating the nature of surface coatings on fine drug powders and the potential in producing novel oral solid dosage forms QuLi 2017 The objective of this thesis was to investigate a mechanical dry powder coating approach to improve flow and fluidization of cohesive powder for producing direct compaction tablets. A fine cohesive ibuprofen powder (D₅₀=25 µm) with a low-melting point (~76°C) was coated with varying coating materials (magnesium stearate (MgSt), l-leucine, sodium stearyl fumarate (SSF) and silica-R972) in order to examine the effects on flow and tabletability of the processed powders. Firstly, ibuprofen powder was dry coated via mechanofusion with between 0.1 to 5% (w/w) MgSt. ToF-SIMS demonstrated high degrees of coating coverage of MgSt on the particle surfaces. Robust tablets could be produced from the mechanofused powders and surprisingly the release rate of drug was not retarded. This is the first study to demonstrate such a single-step dry coating of ibuprofen with MgSt, with promising flow improvement and non-inhibited dissolution rate. Secondly, ibuprofen powder was dry coated with 1% (w/w) of several materials including MgSt, l-leucine, SSF and silica-R972 to screen potential coating materials and develop directly-compacted tablets of high-dose drug. FT4 powder characterisation indicated coating of MgSt, l-leucine and silica-R972 produced improvement in powder flow. ToF-SIMS demonstrated a near-complete layer on the drug particle surface after coating with MgSt and silica-R972. The dissolution rates of all mechanofused powders were enhanced even with a hydrophobic material such as MgSt and silica. Such enhanced dissolution rate was attributed to the lesser agglomeration resulting from the reduced cohesion between the drug particles after mechanofusion. Thirdly, ibuprofen powders with various coating materials (MgSt, l-leucine and silica-R972), PVP and superdisintegrant were co-processed using mechanofusion and then directly compacted into tablets to achieve a single-step tablet production. FT4 indicated substantial improvement in powder flow. Robust tablets were produced from the co-processed ibuprofen and all excipient powders and the dissolution rates of these tablets were enhanced compared to control batch. However, the tablets made with silica-R972-mechanofused powders could not dinsitegrate and release under the same conditions. Finally, l-leucine has been found to have promising capacity of improving flowability of ibuprofen powder via mechanofusion. Such processed powder was able to be compacted into tablets directly. Therefore, a study was proposed to evaluate the influence of particle size of l-leucine (D₅₀ of 10 – 260 µm) on the flowability and tabletability of mechanofused ibuprofen powder. ToF-SIMS demonstrated an increasing trend of coverage level of l-leucine on the drug particle surface with reducing l-leucine particle size. Dissolution data of processed powders were fitted with multi-exponential equation models, representing dissolution from dispersed and agglomerated particle distributions. In conclusion, improvements in ibuprofen powder flowability via mechanofusion can result in a promising trend allowing tablets to be formed by direct compaction and enhanced dissolution rate of both powders and tablets. Surprisingly, coating of hydrophobic guest particles did promote dissolution of powders or corresponding tablets rather than retardance of dissolution rates. Multi-exponential modelling indicated that such improvements in the dissolution performance were attributed to the reduction in agglomerate strength caused by decreasing powder intrinsic cohesion after surface modification.