Liposomes are spherical lipid vesicles constantly gaining ground in drug development as potential drug nanodelivery systems due to their ability to incorporate hydrophilic as well as lipophilic active ingredients. One of the major challenges is liposome production on an industrial scale where spray drying offers great potential. Stemming from the latter, the aim of this master's thesis was to evaluate the effects of different solvents and spray drying parameters on the production of liposomes with predetermined composition in order to obtain information on the possibility of transferring method to the production level.
Based on literature and experiments we found suitable solvents for dissolving phospholipids (distearoyl phosphatidylcholine.(DSPC), distearoyl phosphatidylglycerole sodium salt (DSPG-Na)) and cholesterol. Liposomes were prepared by spray drying the lipid dispersion at varying parameters (air flow rate, feed rate and inlet temperature). The spray dried product was rehydrated in aqueous medium and the resulting liposomes were extruded through polycarbonate membrane. Thermal analysis was performed on spray dry powder and hydrodynamic diameter, polydispersity index and zeta potential of liposomes were measured. In experimental work and data analysis, we followed the principle of experimental design which allows us to obtain maximum amount of information for process and end product evaluation on a small number of experiments.
Based on excipients solubility and ICH guidelines two solvents were selected for spray drying experiments: a mixture of dichloromethane and methanol in 1:1 volume ratio and methanol. The process of dissolving DSPG-Na was accelerated by heating the dispersion to 40 °C. By analysing the resulting liposomes, we found that their properties were influenced by two spray drying parameters. Higher process yield was obtained at lower air flow rate and smaller liposomes were obtained if the inlet gas temperature was raised. The diameter of the resulting liposomes was about 800 nm and decreased to 150 nm after extrusion, while zeta potential remained the same in both cases. The absence of solvent residue in dry product was proved by thermal analysis of samples. The key finding of the master's thesis was that by extrusion of liposomes the effects of spray-drying parameters on the size and polydispersity index of liposomes are practically eliminated.
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