Application of the QbD-based approach in the early development of liposomes for nasal administration

Abstract

In this study, authors adapt the Quality by Design (QbD) concept as well as the Risk Assessment (RA) method to the early development phase of a new nano-sized liposomal formulation for nasal administration with brain target. As a model active agent, a BCS II class drug was chosen to investigate the behaviour of the drugs with lipophilic character. This research presents how to apply this risk-focused approach and concentrates on the first four stages of the QbD implementation. In this way the quality target product profile was defined, the critical factors were identified and an RA was performed. The RA results helped in the factorial design-based liposome preparation by the lipid film hydration method. The prepared liposomes were evaluated (vesicle size, size distribution, and specific surface area). The surface characteristics were also investigated to verify the exactness of the RA and critical factors based theoretical prediction. The results confirm that the QbD approach in liposome development can improve the formulation process. The RA focused predictive approach resulted in a decreased number of studies in practice but in an effective product preparation. Using such innovative design and development models can help to optimise and rationalise the development of liposomes.

Keywords: Lipophilic drug containing liposome; Liposome; Nanocarriers; Nasal administration; Quality by Design; Risk assessment; Risk-based formulation.