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Updated: Jun 9, 2025
Preparation, Administration, and Assessment of In Vivo Tissue-Specific Cellular Uptake of Fluorescent Dye-Labeled Liposomes
Published on: July 30, 2020
Development and optimization of an in vitro release assay for evaluation of liposomal irinotecan formulation
Vivian Juang1, Jingyao Gan1, Ziyun Xia1
1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, United States.
Abstract:
Onivyde®, a pegylated irinotecan liposomal formulation, is approved by the USFDA for treating metastatic pancreatic adenocarcinoma. Despite the substantial interest in developing its generic versions, the unique structural and manufacturing complexities of liposomal formulations pose challenges. In this study, we address this gap by developing a robust in vitro release test (IVRT) using dialysis membrane techniques. The release of Onivyde® is influenced by several key factors, including the composition of the release medium, temperature, initial formulation concentration, the materials and molecular weight cut-offs of dialysis bags, and the pH of the release medium. Our optimized IVRT for Onivyde® incorporates a release medium containing 5 mM ammonium bicarbonate in a HEPES solution with a pH of 7.4. Additionally, the method includes an initial formulation concentration of 4.6 µg/mL and 50 kDa dialysis bags, while maintaining a temperature of 37 °C with continuous agitation at 80 rpm. This optimized IVR assay effectively differentiates between varying qualities of irinotecan liposomal formulations. Our findings contribute to optimizing IVRT for liposomal irinotecan formulations, enabling better quality control procedures. This assay serves as a reliable tool for evaluating generic irinotecan liposomal formulations, aiding in their development and ensuring in vitro comparability.
Insights
A new in vitro release test (IVRT) was developed for Onivyde® (pegylated irinotecan liposomal formulation) to aid generic drug development. This optimized assay ensures quality control and comparability for liposomal irinotecan formulations.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Oncology Therapeutics
Background:
- Onivyde® (pegylated irinotecan liposomal formulation) is FDA-approved for metastatic pancreatic adenocarcinoma.
- Developing generic versions of complex liposomal formulations like Onivyde® presents significant manufacturing and quality control challenges.
- A robust in vitro release test (IVRT) is crucial for evaluating the quality and comparability of generic liposomal drug products.
Purpose of the Study:
- To develop and optimize a reliable in vitro release test (IVRT) for Onivyde® (pegylated irinotecan liposomal formulation).
- To establish critical parameters influencing the in vitro release of irinotecan from liposomal formulations.
- To provide a validated assay for assessing the quality and in vitro comparability of generic irinotecan liposomal formulations.
Main Methods:
- Utilized dialysis membrane techniques to establish the in vitro release profile of Onivyde®.
- Investigated the impact of release medium composition, pH, temperature, initial concentration, and dialysis bag specifications (material, molecular weight cut-off) on drug release.
- Optimized IVRT conditions including a 5 mM ammonium bicarbonate/HEPES buffer (pH 7.4), 4.6 µg/mL initial concentration, 50 kDa dialysis bags, 37°C, and 80 rpm agitation.
Main Results:
- Identified key factors affecting Onivyde® release, including medium composition, temperature, concentration, dialysis bag properties, and pH.
- Developed an optimized IVRT method using specific buffer, concentration, dialysis bag size, temperature, and agitation settings.
- Demonstrated that the optimized IVR assay can effectively differentiate between varying qualities of irinotecan liposomal formulations.
Conclusions:
- The developed IVRT provides a robust and reproducible method for evaluating liposomal irinotecan formulations.
- This assay is essential for ensuring the quality control and in vitro comparability of generic Onivyde® products.
- The findings facilitate the development and regulatory assessment of generic pegylated irinotecan liposomal formulations.
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