Starting volumes from 50mL upwards are applicable, and again high pressures are used for disruption of multilamellar systems. The system

works in a pressure range of 0–200 bar and is equipped with this website heating and cooling systems to control sample temperature during processing [43]. The liposome suspension passes the exchangeable orifices several times (up to thousands of passes). Liposomes are formed in the size range from 50 to 100nm by this process. This technique is suitable for large-scale production and sterile liposome preparation. In contrast to the microfluidizer, where the fluid stream is split and mixed by collision in a mixing chamber, homogenizers work on a different principle. In a homogenizer, the fluid Inhibitors,research,lifescience,medical beam is pressed

with high pressure through an orifice, and this beam collides with a stainless steel wall. The liposome suspension is continuously pumped through the homogenizer system, where high pressures are generated to downsize lipid vesicles [44]. The most prominent scalable downsizing method is Inhibitors,research,lifescience,medical the extrusion. Size reduction is managed under mild and more reproducible conditions compared to those discussed above. In this method, preformed vesicles are forced through defined membranes by a much lower pressure as described in the French press method. Extrusion through polycarbonate filters was first published by Olson et al. in 1979 [45]. Mayer et al. Inhibitors,research,lifescience,medical [19] performed extensive studies on varying lipid compositions and the influence on extrusion behavior and membrane properties. Depending on the apparatus and scale, the diameters of these membranes range from 25 to 142mm. Lipex Biomembranes Inc., now Northern Lipids Inc., invented a vessel system for extrusion which is marketed Inhibitors,research,lifescience,medical from the mL scale to several liters. As suggested for all downsizing methods, liposomes should be extruded above the Tc of the lipid composition; this system can be tempered. The Lipex extruder system is available in a jacketed mode to allow extrusion at higher temperatures. An alternative is the Maximator device, established Inhibitors,research,lifescience,medical by Schneider et al. [46]. It is a continuous extrusion

device 4-Aminobutyrate aminotransferase working with a pumping system. The Maximator consists of a thermostable glass supply vessel directly connected to a pneumatic high pressure piston pump. The latter is driven by either oxygen or nitrogen at pressures below 0.5MPa (5 bar or 75psi). The propellant gas does not come into contact with the liposome suspension. The resulting operating (extrusion) pressure—which can be adjusted via the reduction valve in the control device for the propellant gas (3)—can be as high as 12MPa (120 bar or 1800psi) with the current equipment. All the presented extrusion methods have in common that the reproducibility of downsizing is extremely high. Systems with a heating device can either be used with saturated and unsaturated lipids and are; therefore, all purpose systems.