Multivariate evaluation of the effect of the particle size distribution of an Active Pharmaceutical Ingredient on the performance of a pharmaceutical drug product: a real-case study

Abstract

In the pharmaceutical field, and in particular for inhalation drug products based on Dry Powder Inhaler, the Active Pharmaceutical Ingredient particle size distribution is one of the key parameters to drive the final drug product performance. In this paper the impact of the Active Pharmaceutical Ingredient particle size on the Aerodynamic Particle Size Distribution of the final drug product was evaluated by applying different multivariate approaches. By using both the commonly employed particle size distribution descriptors (D10, D50, D90 and SPAN) and the whole particle size distribution curves it has been demonstrated that the latter gives an information which is easier to understand and interpret.Finally, models estimating the effects of the Active Pharmaceutical Ingredient particle size distribution, device life and drug product dosage on the Aerodynamic Particle Size Distribution of the final drug product were also established.