Dual Centrifugation - A Novel “in-vial” Liposome Processing Technique

Conventional liposome preparation methods bear many limitations, such as poor entrapment efficiencies for hydrophilic drugs, batch size limitations, and limited options for aseptic manufacturing. Liposome preparation by dual centrifugation (DC) is able to overcome most of these limitations. DC differs from normal centrifugation by an additional rotation of the samples during the centrifugation process. Thus, the direction of the centrifugal forces changes continuously in the sample vials. The consequential powerful sample movements inside the vials result in powerful homogenization of the sample. Since this “in-vial” homogenization is optimal for viscous samples, semisolid “vesicular phospholipid gels” (VPGs) are preferred intermediates in the liposome manufacturing by DC. The DC method easily enables aseptic preparation and is gentler as compared to other methods, such as high-pressure homogenization. The method allows very small samples to be prepared, and VPG batches down to 1–5 mg scale have been prepared successfully. VPGs have several applications; they are attractive as depot formulations, or as stable storage intermediates, and can be easily transferred into conventional liposomal formulations by simple dilution. Here, we aim to present the novel DC-liposome technique; the concept, advantages, and limitations; and provide an overview of the experiences of liposome preparation by DC so far