The rheology of hexadecane-in-water emulsions stabilized by montmorillonite platelets was investigated. In these systems excess particles form a network in the continuous phase which strongly dictates their rheological behavior. The emulsions were modified by the addition of NaCl and NaPO to the continuous phase at varying concentrations. Remarkably, changes of up to 3 orders of magnitude in elastic modulus and yield stress of the emulsions were achieved. The droplets retained long-term coalescence stability after the addition of NaCl or NaPO and even after the removal of the continuous phase network. The latter finding shows that the droplets are primarily stabilized by the formation of a solid barrier at the interface. These emulsions are therefore highly versatile formulation materials with an exceptional degree of stability and tunability.

The structural and rheological consequences of adsorbing pyrophosphate anions to the edges and polyetheramines to the faces of montmorillonite platelets in aqueous suspension were investigated. Oscillatory rheology and scattering experiments showed that the two surface treatments act in different regions of the phase diagram and that this can be attributed to modifications of local particle interactions resulting in changes to the behavior and morphology of platelet clusters. The polyetheramine was found to neutralize surface charge, reducing electrostatic repulsion between platelets and therefore allowing them to come into closer proximity. This reduces the effective volume fraction of the clusters and reverses jamming in low ionic strength arrested phases. Conversely, the adsorption of pyrophosphate was found to introduce a high concentration of negative charge to the particle edge, resisting the formation of bonded percolating gels at high ionic strength. The two separate surface chemistries can be applied in parallel with no adverse effects and thus have the potential to be applied to dual functionalization of two-dimensional colloids such as platelets. This has implications for finer formulation design where targeted rheology modification could be achieved by careful selection of chemistry at one surface accompanied by an additional function at the other.

The formation of water-in-water emulsions from the aqueous two phase system containing polyethylene oxide and pullulan, stabilised by montmorillonite platelets, was investigated. A novel approach of preparing the emulsions at non-equilibrium polymer concentrations was successfully utilised to control viscosity during mixing and allow the use of low energy emulsification methods. Polyethylene oxide adsorbed to the platelets much more strongly than pullulan favouring the formation of pullulan-in-polyethylene oxide emulsions which remained stable for a period of weeks. Polarising microscopy and small angle light scattering were used to show that droplets were most likely stabilised against coalescence by the adsorption of randomly oriented aggregates of platelets and against creaming by the formation of chains of droplets bridged by the adsorbed aggregates. Montmorillonite platelets were therefore shown to stabilise water-in-water emulsions and their preference for emulsion type was driven by the adsorption of the polymers to the particle surface.

The formation of hexadecane-in-water emulsions stabilised by montmorillonite platelets was studied. In this system the platelets form a monolayer around the droplets and the droplet size decreases with increasing platelet volume fraction. However, the number of platelets present exceeds that required for monolayer coverage. The kinetics of emulsification were investigated and coalescence of droplets during turbulent mixing was found to continue even after the droplets had reached their ultimate size. Non-spherical droplets, resulting from arrested coalescence, were not observed suggesting that particles may be desorbing from the interface during the turbulent flow. A kinetic model based on a competition between droplet break-up and coalescence, mediated by particle adsorption and desorption, reproduces experimental trends in droplet diameter. The model can be used to predict the most efficient formulation to minimise droplet diameters for given materials and mixing conditions and sheds light on the processes occurring during emulsification in this system.

The aim of the study was to develop a robust and standardized in vitro dissolution methodology for orally inhaled drug products (OIDPs). An aerosol dose collection (ADC) system was designed to uniformly deposit the whole impactor stage mass (ISM) over a large filter area for dissolution testing. All dissolution tests were performed under sink conditions in a sodium phosphate buffered saline solution containing 0.2%w/w sodium dodecyl sulphate. An adapted USP Apparatus V, Paddle over Disk (POD), was used throughout the study. The dissolution characteristics of the ISM dose of a commercial metered-dose inhaler (MDI) and a range of dry powder inhaler (DPI) formulations containing inhaled corticosteroids were tested. The uniform distribution of the validated ISM dose considerably reduced drug loading effects on the dissolution profiles for both MDI and DPI formulations. The improvement in the robustness and discriminatory capability of the technique enabled characterization of dissolution rate differences between inhaler platforms and between different DPI product strengths containing fluticasone propionate. A good correlation between in vivo mean absorption time and in vitro dissolution half-life was found for a range of the inhaled corticosteroids. The ADC system and the reproducible in vitro POD dissolution measurements provided a quantitative-based approach for measuring the relationship between the influence of device and the dispersion characteristics on the aerosol dissolution of low solubility compounds. The in vitro dissolution method could potentially be applied as a dissolution methodology for compendial, quality control release testing, and during development of both branded orally inhaled drug products and their generic counterparts.