Liposomes were produced by an innovative method using supercritical carbon dioxide as a dispersing agent. A quality by design strategy was used to find optimal production conditions with specific parameters (lipid concentration, dispersion volume, agitation rate, temperature and pressure) allowing the production of liposomes with predicted physicochemical characteristics (particles size and PdI). Two conditions were determined with specific production parameters. It was shown that these two conditions allowed the production of liposomes of different compositions and that most of the liposome formulations had size and dispersity in accordance with the prediction values. The condition involving the higher lipid concentration showed a higher variability in terms of size and dispersity. However, this variability remained acceptable. This innovative supercritical method allowed the production of liposomes with physicochemical characteristics similar to those obtained by the conventional thin film hydration method. This new supercritical carbon dioxide method easily scalable in GMP conditions is a one-step production method contrarily to conventional methods which generally need an additional step as extrusion to homogenize the size of liposomes.

译文

脂质体是通过使用超临界二氧化碳作为分散剂的创新方法生产的。通过设计策略的质量来找到具有特定参数 (脂质浓度,分散体积,搅拌速率,温度和压力) 的最佳生产条件,从而可以生产具有预测的理化特性 (颗粒尺寸和PdI) 的脂质体。用特定的生产参数确定了两个条件。表明,这两种条件允许生产不同组成的脂质体,并且大多数脂质体制剂具有与预测值一致的尺寸和分散性。涉及较高脂质浓度的条件在大小和分散性方面显示出较高的变异性。然而,这种可变性仍然是可以接受的。这种创新的超临界方法允许生产具有类似于通过常规薄膜水合方法获得的理化特性的脂质体。这种新的超临界二氧化碳方法在GMP条件下易于扩展,是与常规方法相反的一步生产方法,常规方法通常需要额外的步骤作为挤出步骤以均质化脂质体的尺寸。

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