Protection of aluminum hydroxide during lyophilisation as an adjuvant for freeze-dried vaccines

Lyophilisation of an aluminum hydroxide adjuvant containing formulation for use in vaccine development has been investigated. Novel formulation approaches using disaccharides, polysaccharides, polyols and polymers have been investigated as stabilising excipients to prevent aluminum hydroxide adjuvant from aggregation during a freeze–thaw cycle or the lyophilisation process itself. Amorphous character of the lyophilisates was investigated by wide angle X-ray diffraction. Sedimentation assay, particle size analysis and optical microscopy could show that aluminum adjuvant gel character of selected formulations could be maintained within acceptable quality or stayed the same in some cases. In principle, it could be demonstrated that not less than 10% excipient is necessary to yield good results within applied analytics evaluating the excipients’ protecting qualities. Based on results obtained by this study, the formulations containing trehalose at a concentration of 15 or 20%, dextran, PVP K 25, HES 450 and 200, saccharose and sorbitole along with polysorbate 80 and buffer promise to be good candidates for the protection of aluminum adjuvanted vaccines during exposure to coldness stresses as during freezing or lyophilisation.