Purification of Drug Loaded Liposomal Formulations by a Novel Stirred Cell Ultrafiltration Technique

Background: Presently reported methods for purification of liposomal formulations at laboratory scale have drawbacks of adversely affecting critical quality attributes (CQAs) of liposomes such as particle size, PDI, drug entrapment efficiency, etc., and are also not amenable for large scale processing. Objective: The present study was aimed to explore stirred cell ultrafiltration technique as a novel liposome purification method for removal of unentrapped free drug and excess external aqueous fluid, maintaining the physical integrity of liposomes. Methods: Purification of brimonidine loaded liposomes (model formulation) was performed by stirred cell ultrafiltration method, and its functional performance and impact on liposomal particle size, PDI, and entrapment efficiency were compared with two widely used laboratory scale methods, i.e., ultracentrifugation and centrifugal ultrafiltration. Results: The novel stirred cell ultrafiltration method demonstrated liposomal purification within ~30 min with complete liposomal recovery showing minimal processing impact, i.e., #130;0.25 fold rise in particle size, ~0.5 fold rise in PDI, and ~4% loss in % entrapment efficiency, respectively. Whereas ultracentrifugation and centrifugal ultrafiltration methods resulted in ~4 fold and #131;2 fold rise in particle size, #131;10 fold and #131;5 fold rise in PDI, and #131;25% and ~6% loss in entrapment efficiency, respectively. Conclusion: The unique and product-friendly operational features of stirred cell ultrafiltration method demonstrated simple, rapid, and efficient liposomal purification without affecting CQAs of liposomal vesicles. This method was also evidently found to be product-friendly, rugged, versatile, and scalable up to large production batch processing, overcoming major drawbacks of presently used methods.