Influence of formulation on jet nebulisation quality of alpha 1 protease inhibitor

As foam appears during solution constitution and nebulisation of alpha 1 protease inhibitor (alpha 1 PI), we selected in a previous work, antifoams likely to be associated with an alpha 1 PI solution to be nebulised: span 65 at a 0.025% concentration and cetyl alcohol at a 0.05% concentration associated with tyloxapol at 0.025% concentration. The purpose of this study was, on the one hand to study the influence of the formulation on nebulisation quality by relating physicochemical properties and nebulisation capacity, and on the other hand, to define the alpha 1 PI that will be retained for a clinical study. The properties of the different alpha 1 PI formulations are compared: surface tension, viscosity, time required to constitute the protein solution and pH. Nebulisation quality is evaluated under different operating conditions by measuring the droplet size, the quantity of alpha 1 PI nebulised, nebulisation time and the quantity of alpha 1 PI likely to reach the lungs which was subjected to statistical analysis. The statistical analysis of results indicates that the addition of the cetyl alcohol/tyloxapol mixture improves nebulisation effectiveness by significantly increasing the quantity of drug nebulised and therefore the quantity of alpha PI likely to reach the lungs. It is this formulation that will be retained for clinical trials. We check that the nebuliser and operating conditions influence all the parameters, that is to say the respirable fraction, the quantity nebulised and the nebulisation time. Although there is no interaction between the nebuliser and the formulation, nebulisation quality is the combined result of the formulation, the nebuliser and the operating conditions.