Application of quality by design to formulation and processing of protein liposomes.
Academic Article
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
abstract
Quality by design (QbD) principles were explored in the current study to gain a comprehensive understanding of the preparation of superoxide dismutase (SOD) containing liposome formulations prepared using freeze-and-thaw unilamellar vesicles (FAT-ULV). Risk analysis and D-optimal statistical design were performed. Of all the variables investigated, lipid concentration, cholesterol mol%, main lipid type and protein concentration were identified as critical parameters affecting SOD encapsulation efficiency, while the main lipid type was the only factor influencing liposome particle size. Using a model generated by the D-optimal design, a series of three-dimensional response spaces for SOD liposome encapsulation efficiency were established. The maximum values observed in the response surfaces indirectly confirmed the existence of a specific SOD-lipid interaction, which took place in the lipid bilayer under the following optimal conditions: (1) appropriate membrane thickness and curvature (DPPC liposomes); and (2) optimal "pocket size" generated by cholesterol content. With respect to storage stability, the prepared SOD liposomes remained stable for at least 6 months in aqueous dispersion state at 4C. This research highlights the level of understanding that can be accomplished through a well-designed study based on the philosophy of QbD.
