Cyclodextrin as membrane protectant in spray-drying and freeze-drying of PEGylated liposomes

In this study it was investigated whether hydroxypropyl-β-cyclodextrin (HPβCD) is able to stabilize the liposomal membranes during drying of long circulating polyethylene glycol (PEG) coated liposomes, as compared to the disaccharides trehalose and sucrose. PEGylated liposomes loaded with prednisolone disodium phosphate (PLP) were dried by spray-drying or freeze-drying. The dried powders were tested on their residual moisture content, glass transition temperature and amorphous character. Upon reconstitution the liposomal size, size distribution and drug retention were determined and the results were compared to the characteristics of the formulation solution before drying. In contrast to the disaccharides, HPβCD stabilizes the liposomal membranes of the PEGylated liposomes during the drying process of both spray drying and freeze-drying when present in a lipid:carbohydrate ratio of 1:6 (w/w). The resulting powder can be stored at room temperature. No changes in size and size distribution were seen upon reconstitution of the HPβCD containing formulations. Drying resulted in a minimal leaking of PLP from the liposomes. Its relatively high T′g and Tg of HPβCD, as compared to the disaccharides, make HPβCD an excellent membrane protectant for dry PEGylated liposomal formulations.

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