An Improved Liposome Manufacturing Process

在稳定性、无菌性和成本的约束下，需要大规模的脂质体制造工艺来满足日益增长的脂质体药物输送和控释载体的市场需求。他们建议开发一种改进的大规模脂质体制造工艺。他们建议用近临界或超临界流体(SCF)溶剂取代脂质体制备中使用的有机溶剂来实现这一点。他们还计划评估SCF作为通过高压均质制造脂质体的替代品的使用。在脂质体制造过程中，用超临界流体溶剂置换有机溶剂将减少磷脂和包封剂的降解，并允许快速分离、回收和重复使用溶剂。与现有的制备脂质体的实验室和商业工艺相比，建议的工艺有几个潜在的好处。预期的好处是：不使用有机溶剂；制造的脂质体进行终端灭菌；无氧气氛；用冷却效果取代显著的加热效果；与高压均质相比，压力要求更低；操作和维护成本更低；更高的处理速度；可能形成统一的FATMLV；连续运行的能力；以及可扩展性。

There exists a need for large scale liposome manufacturing processes which can meet the growing market demand for liposomal drug delivery and controlled release vehicles within constraints of stability, sterility and cost. They propose to develop an improved large scale liposome manufacturing process. They propose to do so by replacing the organic solvents used in the preparation of liposomes with near critical or supercritical fluid (SCF) solvents. They also plan to evaluate the use of SCFs as a replacement for liposome manufacturing by high pressure homogenization. The displacement of organic solvents with supercritical fluid solvents in the liposomal manufacturing process will reduce the degradation of the phospholipids and encapsulated therapeutics and allow rapid solvent separation, recovery and reuse. There are several potential benefits to the proposed processes over existing laboratory and commercial processes for the preparation of liposomes. The anticipated benefits are: non-use of organic solvents; terminal sterilization of the manufactured liposomes; an oxygen free atmosphere; replacement of significant heating effects with cooling ones; lower pressure requirements when compared to high pressure homogenization; lower O&M costs; higher speed of processing; the potential formation of uniform FATMLVs; the ability to operate continuously; and scalability.