Milling and co-milling are well known techniques that have potential to enhance the solubility and/or dissolution rate of poorly soluble drugs. There are broadly two aims for this project. The first was to develop an understanding of how individual and combination of techniques may be used to explore the impact of milling on particle characteristics (including phase changes, fractures and change in particle size) as a function of milling time/speed, for a range of single powder materials. Anhydrous (lactose, sucrose), monohydrate (lactose) and dihydrate (trehalose) excipients and a poorly soluble drug (ibuprofen), were chosen as model substrates. Each material was micronized by ball-milling (for various time durations and milling speeds) and then characterized by a range of techniques, specifically, SEM, DSC, TGA, THz and dielectric spectroscopy. The second aim of the project was to investigate the impact of milling and co-milling on the solubility and dissolution rate of ibuprofen after co-milling with a variety of excipients (polymer and surfactants). The principle findings of this programme of work can be summarized as follows: i) ball milling of lactose monohydrate produces nano-structured systems with a mixture of damaged crystals and amorphous phase, that can be characterised by dielectric relaxation spectroscopy (DRS), ii) THz spectroscopy provides estimates for residual crystallinity in lactose monohydrate that were much lower than the estimates from the thermal techniques. Such estimates of residual crystallinity are considered to be more reliable given the fact that the spectroscopic measurement characterizes the material in its native state, whereas thermal techniques require a heating process, which tend to induce de-vitrification and mutarotation of lactose. In case of anhydrous materials, while there was agreement between thermal and THz techniques at long milling times, it was shown that the THz technique was susceptible to moisture absorption and crystallization at short milling times, iii) In the molecular dynamics of milled sugars studied by DRS, the structural relaxation is not visible in the vicinity of glass transition, however the secondary relaxation (β) process is equally capable and provided molecular dynamics in term of activation energy changes. The activation energies of beta process of both lactose and sucrose are least affected by milling time, but the higher activation energies for sucrose as compared with lactose show that sucrose has lower propensity to re-crystallize than lactose during post milling storage, iv) Ibuprofen can be assayed by UV-method in the presence of interfering (in absorption) substance by applying multivariate method involving the calculation of concentration factors and v) Co-milling with soluplus has increased the in the solubility of ibuprofen by ~20% and dissolution rate ~50% in 30 min, while these values are ~5% and 30%, respectively in case of co-milling with HPMC.

Beetle-killed trees and woody residues degenerate and may lead to wildfires and uncontrolled CO2 emission. Woody biomass is known as a neutral CO2 solid fuel since it generates the same amount of CO2 that takes from atmosphere during its growing up. Cofiring woody biomass with coal in existing coal power plants is a reasonable solution to reduce the net amount of CO2 emission and decrease the risk of wildfires. However, there are some challenges ranging from providing and handling the woody biomass to the operation of cofiring woody biomass with coal. Co-milling of the fuels and ash deposition on the heat exchanger surfaces during cofiring are among the most critical challenges. A CFD model simulated the behavior of the pulverized particles and evaluate the impact of geometry and operational changes on mill performance. In addition, we measured the ash deposit rate derived from cofiring woody biomass with coal in a pilot combustor (1500 kW) and full-scale furnace. Moreover, we developed a model to predict ash deposit rate during combustion of coal and its blend with a variety of biomass. The post-processing analysis of CFD modelling of co-milling woody biomass with coal shows that the entrained large woody biomass particles exit the pulverizer along with the fine coal particles due to their lower density than that of coal particles. Some simple geometry and operational changes can optimize mill performance by reducing the number of large biomass particles in the product stream. Therefore, it makes the particle size distribution (PSD) of the product stream of co-milling more like that of coal. The collected data set of fly ash particles and ash deposit samples shows that the ash formation and deposit rates were not impacted significantly by cofiring woody biomass with coal. The concentration of alkali metals in the ash aerosol during cofiring was slightly higher than that of coal. Cofiring in pilot scale combustor made a tri-modal PSD of ash aerosol particles; however, the distribution was bimodal in the full-scale boiler. The ash deposit rates during cofiring in 1500 kW combustor were higher (30 to 70%) at locations closer to the burner at short operation times. Our developed model of ash deposit rate investigated two types of stickiness models of fly ash particles to the surface of heat exchanger: melt fraction stickiness model (MFSM) and kinetic energy stickiness model (KESM). The developed model suggested that the MFSM, which is based on the melt fraction of ash and our novel approach to condensation of alkali vapor species, was more accurate in predicting ash deposit rate of a variety of fuel combustion of a 100-kW combustor. The model calculated four mechanisms: inertial impaction, thermophoresis, condensation, and eddy impaction.