Nanotechnology Research Lab, Department of Pharmacy, Shri G.S. Institute of Technology and Science, 23- Park Road, Indore - 452003 (M.P.),India.
Pharm Nanotechnol. 2021;9(5):347-360. doi: 10.2174/2211738509666211124145848.
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.
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.
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.
The novel stirred cell ultrafiltration method demonstrated liposomal purification within ~30 min with complete liposomal recovery showing minimal processing impact, i.e., ˂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 ˃2 fold rise in particle size, ˃10 fold and ˃5 fold rise in PDI, and ˃25% and ~6% loss in entrapment efficiency, respectively.
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.
目前报道的实验室规模下脂质体制剂的纯化方法存在一些缺点，会对脂质体的关键质量属性（CQAs）产生不利影响，例如粒径、PDI、药物包封效率等，并且不适合大规模处理。
本研究旨在探索搅拌式细胞超滤技术作为一种新型的脂质体纯化方法，用于去除未包封的游离药物和过量的外部水相，同时保持脂质体的物理完整性。
采用搅拌式细胞超滤法对布比卡因载脂质体（模型制剂）进行纯化，并将其功能性能和对脂质体粒径、PDI 和包封效率的影响与两种广泛使用的实验室规模方法（即超速离心和离心超滤）进行比较。
新型搅拌式细胞超滤法在约 30 分钟内即可实现脂质体的纯化，并且脂质体的回收率很高，表明处理影响最小，即粒径仅增加了 ˂0.25 倍、PDI 增加了约 0.5 倍、包封效率损失了约 4%。而超速离心和离心超滤法则导致粒径增加了约 4 倍和 ˃2 倍、PDI 增加了 ˃10 倍和 ˃5 倍、包封效率损失了 ˃25%和约 6%。
搅拌式细胞超滤法具有独特的、对产品友好的操作特点，可实现简单、快速、高效的脂质体纯化，而不会影响脂质体囊泡的 CQAs。该方法还明显具有产品友好、坚固、多功能和可扩展到大生产批量处理的特点，克服了目前使用方法的主要缺点。
