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A novel in vitro release test methodology for a liposome formulation was developed using a columnswitching high-performance liquid chromatography (HPLC) system. Doxorubicin (DXR) liposome formulations were used as a model. A DXR liposome formulation was dispersed into a release medium, and the dispersion fluid was directly injected at predetermined time points into the column-switching HPLC system. To evaluate the release profile, this system can be used for determining the released and encapsulated DXR in the liposome formulation separately. Comparison with a conventional in vitro release test methodology by dialysis revealed that the methodology developed by column-switching HPLC had no rate-limiting process of membrane permeation of the drug (which is occasionally observed in the dialysis method). The in vitro release profiles of DXR liposome formulations were well characterized using the method developed by column-switching HPLC, and different in vitro release characteristics were revealed. The developed method did not require a large amount of sample or a complicated pretreatment. In addition, the developed columnswitching HPLC system was applicable for characterization of the encapsulation profile of liposome formulations.Key words doxorubicin; Doxil ® ; dialysis; solid-phase extraction; encapsulation Several studies of pharmaceutical formulations for drugdelivery systems (DDS), such as liposomes, microspheres, and nanosuspensions, have been conducted. Their advantages, such as targeted/controlled delivery, enhanced efficacy, and reduced toxicity, have been verified. [1][2][3][4] However, the number of approved and marketed pharmaceutical products with DDS technology is limited. The reasons for this are thought to be the difficulty of robust mass production as well as the lack of sophisticated quality control accompanied by a deep understanding of in vitro and in vivo characteristics. With regard to liposome formulations, the enhanced permeability and retention (EPR) effect of polyethylene glycol-conjugated liposomes has been demonstrated in several studies, and are very attractive as passive targeting methods of antitumor agents. [5][6][7][8][9] Considerable efforts are being made for the development of several administration routes for liposomes, such as inhalational, transdermal, and ocular in addition to injection. [10][11][12][13][14] In contrast, analytical technology for liposome formulations may not be sufficiently mature to assure efficacy and safe performance as well as to direct the optimization of formulations or improvements in manufacturing processes. Drug release characteristics are considered to be one of the important properties to assure the performance of liposome formulations. 15)These characteristics may change depending on the lot-to-lot variation of ingredients and/or changes in manufacturing processes such as scale-up. The importance of evaluation of the in vitro release characteristics is increasing and it is one of the regulatory requirements. [16][17][18][19] Although in vitro re...