Application of quality by design to formulation and processing of protein liposomes.
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 4°C. This research highlights the level of understanding that can be accomplished through a well-designed study based on the philosophy of QbD.
Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, CT 06269, USA. xiaoming.xu@fda.hhs.gov
Xiaoming
X
Xu
Antonio P
AP
Costa
Mansoor A
MA
Khan
Diane J
DJ
Burgess
D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D005615:Freezing; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008962:Models, Theoretical; D010316:Particle Size; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
D000975:Antioxidants; D008055:Lipids; D008081:Liposomes; D002784:Cholesterol; D013482:Superoxide Dismutase