Annabel Flook1, Daniel Lock
1 University of Bath, Claverton Down, Bath, BA2 7AY
Summary
Understanding the effects of three physicochemical properties of formulations: surface tension, conductivity and viscosity, on vibrating-mesh nebulisation has previously employed a ‘one variable at a time’ (OVAT) approach. These formulations have used a range of components as physicochemical property modifiers and, as such, inter- and intra-literature comparisons are unsuitable for the exploration of physicochemical property interactions and their influences on nebulisation. Using Design of Experiment (DoE) methodology, a predictive model has been developed to parameterise and independently adjust the three physicochemical properties in the form of a generic formulation. The prepared formulations were hypothesised to replicate the output rate (OR) of any formulation with equivalent physicochemical properties in Vectura’s FOX® vibrating-mesh nebuliser device. The model successfully mapped three active formulations to their parameterised generic formulations. When nebulised, two generic formulations adequately replicated the OR of their active counterparts (a protein-based formulation and a mucopolysaccharide), whereas one generic and active formulation pair (a small molecule formulation) showed a large difference in OR. Therefore, the three physicochemical properties alone were deemed unsuitable as predictors of OR for every formulation. The impact of viscosity on OR was also assessed. When comparing formulations comprising of the same components (the generic formulations), a strong linear relationship was observed. However, this relationship was not applicable to formulations comprising of differing components (the active formulations) and suggest caution should be exercised when comparing the OR of different formulations with respect to their physicochemical properties. Alternative properties, such as interfacial tension, should be explored to fully understand nebulisation and advance formulation development approaches.
Key Message
Three generic formulations were prepared to mimic the physicochemical properties: viscosity, surface tension and conductivity of three active formulations. When nebulised, they did not always show comparable output rates, suggesting alternative physicochemical properties may give a better indicator of a formulation’s nebulisation performance, leading to improved formulation development.