The effects of lyophilization on the stability of liposomes containing 5-FU

• Published in: International journal of pharmaceutics Vol. 291; no. 1; pp. 79 - 86
• Main Authors: Glavas-Dodov, M., Fredro-Kumbaradzi, E., Goracinova, K., Simonoska, M., Calis, S., Trajkovic-Jolevska, S., Hincal, A.A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 03.03.2005; Elsevier
• Subjects: 5-FU; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Cryoprotectants; Drug Carriers; Drug leakage; Drug Stability; Fluorouracil - chemistry; Fluorouracil - pharmacokinetics; Freeze Drying - methods; General pharmacology; Liposomes; Liposomes - chemistry; Lyophilization; Medical sciences; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Solubility; Stability; Sucrose - chemistry; Technology, Pharmaceutical - methods; Stability; Liposomes; Lyophilization; Drug leakage; Cryoprotectants; 5-FU; Drug; Pharmaceutical technology; Liposome; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2004.07.045

Multilamellar liposomes containing 5-fluorouracil (5-FU) were prepared by modified lipid film hydration method and were lyophilized with or without saccharose as cryoprotectant. The effect of lyophilization on the stability of liposomes was evaluated by comparing the vesicle size, encapsulation efficiency and the drug release rate before and after lyophilization/rehydration. The process of lyophilization, without cryoprotectant, resulted in particle size increase and significant content leakage. By the addition of saccharose, the lipid bilayers become more stable and less permeable to the encapsulated drug, saccharose imparted 5-FU retention of about 80% after lyophilization/rehydration. Freeze-drying did not affect the particle size of liposomes containing saccharose as cryoprotectant. The drug release profiles of rehydrated liposomes followed Higuchi's square root model. Also, the obtained release profiles were all biphasic: a rapid initial drug release phase (burst release of the portion of the drug that leaked out of liposomes during the lyophilization) was followed by a slower, approximately constant drug release phase (zero-order kinetics).