An investigation into the effect of particle and formulation properties on the performance of pharmaceutical powders using novel experimental and modelling techniques

This thesis provides a piece of comprehensive information on the interrelationship between particle properties, formulation properties, and the performance of pharmaceutical powders. Three main performance categories were investigated; these include flow, disintegration, and dissolution. The effect of formulation properties on the dissolution performance of a pharmaceutical formulation containing a low soluble active pharmaceutical ingredient was explored. A novel, dynamic contact angle measurement technique was used to understand wetting behaviour and provide correlations with dissolution testing using biorelevant dissolution media. In addition, this thesis explored the link between the microstructure obtained by X-ray microtomography and the dissolution performance. The thesis also investigates how formulation properties such as disintegrant type and the amount of lubricant affects the disintegration behaviour of pharmaceutical tablets by coupling a novel surface imaging instrument with an in-line particle size analyser.

This thesis also presents novel data analysis techniques with the aim to build a modelling framework that can be used to relate particle properties of pharmaceutical powders such as particle size and shape to their flow performance. Radial basis function (RBF) and neural network techniques were used to achieve this goal. Traditional data analysis techniques such as multivariate data analysis were used to build correlations between particle properties and powder performance. This is of great importance in the early stages of drug discovery activities. The information from this thesis therefore demonstrates how novel experimental and modelling techniques can be used to related particle properties and formulation properties to the performance of pharmaceutical powders.