Purpose

The study utilized non-ionic polymer macrogol to transform the surface properties of the DepoFoam drug carrier system, developing “surface-remodeled DepoFoam (SR-DFO)” following quality by design (QbD) principles. The primary objectives were to prolong drug delivery, reduce sudden releases, and enhance the overall quality and stability of DepoFoam. The research hypotheses are centered on the capability of macrogol-based surface modification to create an optimized drug delivery system with improved stability, extended drug release, and enhanced pharmacokinetic properties.

Methods

In this research, surface remodeling was achieved through a series of processes, including high-shear homogenizer-assisted double emulsification, PEGylation, and purification. The resulting SR-DFO formulations were comprehensively characterized for critical quality attributes. Optimization was conducted using the Box-Behnken design, resulting in significant enhancements in both quality and stability compared to conventional liposomes and unmodified DepoFoam.

Results

Comprehensive product characterization validates anticipated quality parameters: entrapment efficiency (86.16 ± 0.44%), drug-loading capacity (25.28 ± 0.07%), vesicle size (40.47 ± 0.1 µm), polydispersity index (PDI) of 0.051 ± 0.03, lipocrit of 90.67 ± 0.26%, and zeta potential of − 31.25 ± 3.25 mV. Remarkably, macrogol-based SR-DFO consistently sustains drug release above 90% for 168 h, devoid of sudden spikes, and maintains stability at 4 °C for 180 days. Mathematical models confirm drug release mechanisms’ validity. Moreover, this study emphasizes the critical influence of key materials like macrogol, phospholipids, triglycerides, and process variables on shaping product quality.

Conclusion

These findings highlight the inventive promise of macrogol-coated DFO in transforming drug delivery, quality, and stability. This research, driven by a well-formed hypothesis, meticulous execution, and precise data analysis, opens new horizons in polymer-based DepoFoam systems.

Graphical Abstract

First author: Jebastin Koilpillai, M.Pharm.

中文翻译：

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表面工程和优化 DepoFoam 系统：稳健的质量设计方法，可实现最佳药物输送、稳定性和质量

目的

该研究利用非离子聚合物聚乙二醇来改变DepoFoam药物载体系统的表面特性，遵循质量源于设计（QbD）原则开发了“表面重塑DepoFoam（SR-DFO）”。主要目标是延长药物递送、减少突然释放并提高 DepoFoam 的整体质量和稳定性。研究假设集中在基于聚乙二醇的表面改性的能力上，以创建具有改进的稳定性、延长的药物释放和增强的药代动力学特性的优化的药物递送系统。

方法

在本研究中，表面重塑是通过一系列过程实现的，包括高剪切均质机辅助的双重乳化、聚乙二醇化和纯化。对所得 SR-DFO 配方的关键质量属性进行了全面表征。使用 Box-Behnken 设计进行优化，与传统脂质体和未修饰的 DepoFoam 相比，质量和稳定性显着提高。

结果

全面的产品表征验证了预期的质量参数：包封率 (86.16 ± 0.44%)、载药量 (25.28 ± 0.07%)、囊泡大小 (40.47 ± 0.1 µm)、多分散指数 (PDI) 0.051 ± 0.03、脂质比容 90.67 ± 0.26%，zeta 电位为 − 31.25 ± 3.25 mV。值得注意的是，基于聚乙二醇的 SR-DFO 在 168 小时内始终将药物释放维持在 90% 以上，没有突然的峰值，并在 4°C 下保持稳定性 180 天。数学模型证实了药物释放机制的有效性。此外，本研究强调了聚乙二醇、磷脂、甘油三酯等关键材料和工艺变量对产品质量的关键影响。

结论

这些发现凸显了聚乙二醇涂层 DFO 在改变药物递送、质量和稳定性方面的创造性前景。这项研究由完善的假设、细致的执行和精确的数据分析驱动，为基于聚合物的 DepoFoam 系统开辟了新的视野。

图形概要

第一作者：Jebastin Koilpillai，药学硕士。