Development of a Flow-Through USP-4 Apparatus Drug Release Assay to Evaluate Doxorubicin Liposomes
| Autor: | Wenmin Yuan, Anna Schwendeman, Rui Kuai, Wenlei Jiang, Yue Yuan, Zhipeng Dai, Francis C. Szoka, Nan Zheng, Charles O. Noble, Mark E. Hayes |
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| Rok vydání: | 2015 |
| Předmět: |
Drug
media_common.quotation_subject Chemistry Pharmaceutical Drug Compounding Pharmacology toxicology Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Polyethylene Glycols 03 medical and health sciences 0302 clinical medicine Innovator polycyclic compounds medicine Technology Pharmaceutical Doxorubicin Particle Size Chromatography High Pressure Liquid media_common Liposome Chromatography Antibiotics Antineoplastic Chemistry technology industry and agriculture 021001 nanoscience & nanotechnology carbohydrates (lipids) Drug Liberation Solubility Liposomes Drug release Ethanesulfonic acid Manufacturing methods 0210 nano-technology medicine.drug |
| Zdroj: | The AAPS journal. 19(1) |
| ISSN: | 1550-7416 |
| Popis: | Doxil® is a complex parenteral doxorubicin (DOX) liposome formulation approved by the FDA. For generic doxorubicin liposomes, analyzing the release profile of DOX is important for quality control and comparability studies. However, there is no robust standard drug release assay available for doxorubicin liposomes. In this study, we describe a USP-4 apparatus assay capable of discriminating DOX liposomal formulations based on release profile. Establishment of the assay was hindered by limited DOX release from liposomes in physiological conditions at 37°C. The addition of NH4HCO3 to the release media facilitated DOX release proportionally to the salt concentration added but caused precipitation of released drug in USP-4 apparatus. Precipitation of DOX was avoided by adding hydroxypropyl-cyclodextrin (HP-CD) to the release medium. We optimized conditions for DOX release by varying a number of parameters such as: concentration of HP-CD, testing temperature, and concentration of tested samples. The optimized release medium contained: 100 mM NH4HCO3, 75 mM 2-(N-morpholino) ethanesulfonic acid (MES) and 5% w/v HP-CD, 5% w/v sucrose, 0.02% w/v NaN3 (pH 6). The drug release assay was performed at 45°C. The optimized release assay can discriminate between DOX liposomal formulations of different compositions, physicochemical properties, and prepared by different manufacturing methods. This indicates that the assay could be used to compare DOX release from generic DOX formulations to the innovator product Doxil®. |
| Databáze: | OpenAIRE |
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