Pall Europe, 5, Harbourgate Business Park, Southampton Road, Portsmouth PO6 4BQ, United Kingdom
Pall Europe, 5, Harbourgate Business Park, Southampton Road, Portsmouth PO6 4BQ, United Kingdom.
PDA J Pharm Sci Technol. 2021 Mar-Apr;75(2):128-140. doi: 10.5731/pdajpst.2020.011866. Epub 2020 Sep 30.
Liposomes are increasingly being investigated and implemented as injectable drug delivery systems. The preferred method for sterilizing injectable drug formulations using liposomes is to use filtration. However, because of the size of liposomes and their physicochemical properties, this can be challenging with sterilizing-grade filters rated at 0.2 µm. Filter validation studies with injectable liposomes have shown a higher likelihood of premature filter blockage and bacterial penetration compared to other parenteral drug types. Consequently, a greater understanding of the sterilizing filtration of liposomes is required so that appropriate decisions are made concerning the selection and validation of sterilizing-grade filters for these applications. In this work, Lipoid S100 liposomes were produced using a microfluidization technique without any encapsulated drug (empty) to investigate their filtration through a polyethersulfone filter. In order to improve the sterilizing-grade filtration of liposomes, optimization of both the filtration process and the formulation characteristics is important. To show this, the effect of the different filtration conditions/parameters (prefiltration, serial filtration, differential pressure, inlet pressure) and liposome characteristics such as size and size distribution on filtration were examined. For example, by decreasing the size of the liposome from 179.0 to 127.3 nm, the volumetric throughput (L/m) was increased by more than 40-fold. Or by increasing the differential pressure, the volumetric throughput was improved significantly by more than 18-fold (0.7 to 4.1 bar) and in another experiment by more than 10-fold (0.3 to 2.1 bar). In addition, the benefit of using higher differential pressure on the liposome transmission through various sterilizing-grade membranes was shown.
脂质体作为可注射药物传递系统越来越受到关注和应用。使用过滤法对脂质体进行灭菌处理是首选方法。但是，由于脂质体的大小及其物理化学性质，使用 0.2 µm 灭菌级过滤器可能具有挑战性。对可注射脂质体的过滤验证研究表明，与其他注射用药物类型相比，脂质体更容易出现过早的过滤器堵塞和细菌渗透。因此，需要更深入地了解脂质体的灭菌过滤，以便就这些应用中灭菌级过滤器的选择和验证做出适当的决策。在这项工作中，使用微流化技术生产了没有包裹药物的 Lipoid S100 脂质体（空脂质体），以研究其通过聚醚砜过滤器的过滤情况。为了提高脂质体的灭菌过滤效果，优化过滤工艺和配方特性非常重要。为了证明这一点，研究了不同过滤条件/参数（预过滤、串联过滤、压差、入口压力）和脂质体特性（如大小和粒径分布）对过滤的影响。例如，通过将脂质体的粒径从 179.0 nm 减小到 127.3 nm，体积通量（L/m）增加了 40 多倍。或者通过增加压差，体积通量显著提高了 18 倍以上（0.7 至 4.1 bar），在另一个实验中提高了 10 倍以上（0.3 至 2.1 bar）。此外，还展示了在各种灭菌级膜中使用更高压差对脂质体传输的益处。
