Development of a flow-through USP 4 apparatus drug release assay for the evaluation of amphotericin B liposome
| Autor: | Ran Ming, Nan Zheng, Charles O. Noble, Zhipeng Dai, Yayuan Liu, Wenmin Yuan, Anna Schwendeman, Jie Tang, Wenlei Jiang, Santhanakrishnan Srinivasan, Francis C. Szoka, Mark E. Hayes |
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| Rok vydání: | 2018 |
| Předmět: |
Drug
Antifungal Agents media_common.quotation_subject Chemistry Pharmaceutical Pharmaceutical Science 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Development Amphotericin B medicine Particle Size media_common HEPES Liposome Chemistry Drug release rate General Medicine 021001 nanoscience & nanotechnology In vitro Drug Liberation Drug release 0210 nano-technology Biotechnology medicine.drug Homogenization (biology) |
| Zdroj: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 134 |
| ISSN: | 1873-3441 |
| Popis: | AmBisome® is a liposomal formulation of amphotericin B (Amp B), a complex parenteral antifungal product with no US FDA approved generic version available to date. For generic Amp B liposomal product development, examination of the drug release profile is important for product quality control and analytical comparability evaluation with the reference listed drug. Yet, there is no standardized in vitro drug release (IVR) assay currently available for Amp B liposomes. In this study, we describe the development of a USP-4 apparatus-based IVR assay capable of discriminating liposomal Amp B formulations based on the drug release profile. The goal of the IVR assay development was to identify release media compositions and assay temperatures capable of facilitating 70–100% of drug release from AmBisome® in 24 h without Amp B precipitation or disruption of liposome structure. We found that an addition of 5% w/v of γ-cyclodextrin to the release media of 5% sucrose, 10 mM HEPES, and 0.01% NaN3 (pH = 7.4) prevented Amp B precipitation and facilitated drug release. Increased IVR assay temperature led to increased drug release rate, and 55 °C was selected as the highest temperature that induced drug release close to our target without causing product precipitation. The developed IVR assay was used to discriminate between drug release rates from AmBisome® and micellar Amp B products like Fungizone® and Fungcosome. The IVR assay was also capable of discriminating between Amp B liposomes with the same composition as AmBisome® but prepared by either extrusion or homogenization processes, both of which resulted in measurable liposomal particle size heterogeneity and Amp B concentration differences. Finally, the USP-4 IVR assay was used to compare Amp B release profiles between AmBisome® and two generic products approved in India, Amphonex® (Bharat Serums and Vaccines Ltd.) (f2 = 66.3) and Phosome® (Cipla Ltd.) (f2 = 55.4). Taken together, the developed USP-4 IVR assay can be a useful tool for drug release profile characterization in generic liposomal Amp B formulation development. |
| Databáze: | OpenAIRE |
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