title: Designing a novel in vitro drug-release-testing method for liposomes prepared by pH-gradient method.
abstract: In order to evaluate the drug-release behavior from pH-gradient liposomal formulation, a simple release-testing method without using biological components was newly designed on the basis of inversed ammonia gradient principle. Various factors influencing drug-release (releasing factor) were examined. As a result, releasing factor's concentration, pH, osmolarity in test fluid, and releasing factor's structure were found to be the critical factors to be optimized. Various vincristine-loaded liposomes with different lipid compositions or with different lipid/cholesterol ratio were tested for drug-release behavior and successfully obtained drug-release profiles reflecting differences in the physicochemical properties of individual liposomes. Furthermore, since the comparative release study of vincristine-loaded liposomes and doxorubicin-loaded liposomes could reproduce the phenomena as other researchers recently reported, a possibility was suggested for the proposed method to estimate the physicochemical status of drug inside of liposomes. Proof of concept study concluded, as a whole, that the novel release-testing method would be useful for a formulation study and also useful as a tool for the quality assurance or quality control in the manufacturing of pH-gradient liposomal products.
authors.affiliation: Terumo Corporation, R&D Center, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, 4 Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshino
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamashita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kasukawa
mesh_terms: D000641:Ammonia / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D015394:Molecular Structure; D009994:Osmolar Concentration; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014750:Vincristine / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008055:Lipids; D008081:Liposomes; D014750:Vincristine; D000641:Ammonia; D004317:Doxorubicin