INFLUENCE OF DIFFERENT SUGAR CRYOPROTECTANTS ON THE STABILITY AND PHYSICO-CHEMICAL CHARACTERISTICS OF FREEZE-DRIED 5-FLUOROURACIL PLURILAMELLAR VESICLES

Lyophilization increases the shelf-life of liposomes by preserving it in a dry form as lyophilized cake tobe reconstituted with water immediately prior to administration. Aiming at increasing stability andavailability of 5-Fluorouracil liposomal products, 5-Fluorouacil Stable Plurilamellar Vesicles wereprepared. Freeze dried liposomal dispersions were prepared with or without cryoprotectants. Thecryoprotectants used were glucose, mannitol or trehalose in 1, 2 and 4 grams per gram phospholipids. Theresults showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult toreconstitute, in comparison with fluffy cakes which reconstituted easily and quickly when usingcryoprotectants. The percentage of 5-Fluorouracil retained in liposomes freeze-dried withoutcryoprotectants was 18.29% ± 0.96% and the percentage of 5-Fluorouracil retained in stable plurilamellarvesicles was 31.22% ± 0.62% using 4 grams trehalose as cryoprotectant per gram of lipid. Physicochemicaland release stability studies showed superior potentials of the lyophilized product afterreconstitution in comparison to dispersion product. It may be concluded that all tested sugars havecryoprotectant effects that stabilized liposomes in the freeze dried state, where trehalose offered the mostsuperior cryoprotectant effect for freeze dried 5-fluorouracil liposomes.