Liposome preparation using a hollow fiber membrane contactor—Application to spironolactone encapsulation

• Published in: International journal of pharmaceutics 2011-08, Vol.415 (1), p.53-61
• Main Authors: Laouini, A., Jaafar-Maalej, C., Sfar, S., Charcosset, C., Fessi, H.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Drug Carriers - chemistry; Drug Compounding - methods; drug therapy; drugs; encapsulation; General pharmacology; Hollow fiber module; Hydrophobic and Hydrophilic Interactions; hydrophobicity; Liposome; Liposomes; Medical sciences; Membrane contactor; Membranes, Artificial; Microscopy, Electron, Transmission; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; phospholipids; Phospholipids - chemistry; Polypropylenes - chemistry; Scale-up; Solubility; Spironolactone; Spironolactone - administration & dosage; Surface Properties; transmission electron microscopy; zeta potential
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.05.034

. Preparation of liposomes using a membrane contactor. [Display omitted] ► We present a novel liposome preparation strategy using a hollow fiber module. ► The technique is fast, reproducible and has a potential for industrial production. ► We studied the influence of process parameters on liposome characteristics. ► High entrapment efficiency was achieved when filling liposomes with spironolactone. ► Spironolactone release from liposomes was rapid and complete within 5 h. In this study, we present a novel liposome preparation technique suitable for the entrapment of pharmaceutical and cosmetic agents. This new method uses a membrane contactor in a hollow fiber configuration. In order to investigate the process, key parameters influence on the liposome characteristics was studied. It has been established that the vesicle size distribution decreased with the organic phase pressure decrease, the phospholipid concentration decreases and the aqueous to organic phase volume ratio increases. Liposomes were filled with a hydrophobic drug model, spironolactone that could be used for a paediatric medication. The mean size of drug-free and drug-loaded liposomes was, respectively, 113 ± 4 nm and 123 ± 3 nm. The zeta potential of drug-free and drug-loaded liposomes was, respectively, −43 ± 0.7 mV and −23 ± 0.6 mV. High entrapment efficiency values were successfully achieved (93 ± 1.12%). Transmission electron microscopy images revealed nanometric sized and spherical shaped oligo-lamellar vesicles. The release profile showed a rapid and complete release within about 5 h. Additionally, special attention was paid on process reproducibility and long term lipid vesicles stability. Results confirmed the robustness of the hollow fiber module based technique. Moreover, the technique is simple, fast and has a potential for continuous production of nanosized liposome suspensions at large scale.