A step forward towards the development of stable freeze-dried liposomes: a quality by design approach (QbD)

Abstract

This study highlights the advantages of using a Quality by Design (QbD) approach in order to gain a more comprehensive understanding of the freeze-drying process of pravastatin-loaded long-circulating liposomes (LCL-PRAV). Within the QbD paradigm, the present study aimed to establish the design space for the optimization of freeze-dried LCL-PRAV by means of Design of Experiment (DOE). The encapsulated solute retention (ESR), the average particle size, and zeta potential after freeze-drying, the residual moisture content, the macroscopic cake appearance, the glass transition temperature (T_g) of the freeze-dried cake, and the primary drying time were defined as critical quality attributes (CQAs) for the freeze-dried final product. Further on, the influence of lyoprotectant type, freezing rate, shelf temperature during primary drying, and the presence of an annealing step on the CQAs was investigated through a 21-run D-optimal experimental design. Three-dimensional response surfaces were generated to complete the statistical analysis and for a better understanding of the influence of variables and their interactions on the responses. The developed model was then used to build the design space for the freeze-dried liposomes, within which the product quality was assured and the process variability was minimized.

Keywords:

• Freeze-drying
• liposomes
• optimization
• QbD
• design space
• DoE
• response surface methodology

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the UEFISCDI (Romanian Ministry of Education, Research and Innovation), project number PN-II-PT-PCCA-2011-3.2-1060.