Quality by Design as a Tool in the Optimisation of Nanoparticle Preparation-A Case Study of PLGA Nanoparticles.

Nanoparticles can be used as drug carriers in various applications (e.g., in pulmonary drug delivery and mucosal vaccination). For further investigations, such as drug release studies, as well as for cell and tissue targeting, particles with defined properties are needed. The purpose of the study was to show a multi-step systematic method utilising quality by design to ensure the quality of ovalbumin loaded polylactic-co-glycolic acid nanoparticles (OVA-PLGA-NP), which can be delivered to the lung, and to gain knowledge of the preparation method (double-emulsion solvent evaporation method) in an early development process. Within a definitive screening design, several process parameters (OVA, PLGA and stabiliser concentrations, stirring time and stirring speed of inner emulsion and stirring time and stirring speed of double emulsion) were varied to analyse their impact on resulting properties (z-average, PDI, loading efficiency and loading capacity). The results showed that the preparation of the inner emulsion mainly influenced the drug loading, while the parameters of the second emulsifying step controlled the size. Then a central composite response surface design was used to achieve a predictable OVA-PLGA-NP with an average particle size of 700 nm and high drug-loading. This also enabled the demonstration of curvature and interaction of the stabiliser and the PLGA concentration.