Supercritical antisolvent-fluidized bed for the preparation of dry powder inhaler for pulmonary delivery of nanomedicine.
Supercritical antisolvent-fluidized bed for the preparation of dry powder inhaler for pulmonary delivery of nanomedicine.
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DOI：
10.1016/j.ijpharm.2023.123580
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发表时间：
2023-11
影响因子：
5.8
通讯作者：
Zhimin Ma;Xuejuan Zhang;Lu Ping;Zicheng Zhong;Xiubing Zhang;Xiaodong Zhuang;Guanlin Wang;Qiupin Guo;Shaofeng Zhan;Zhenwen Qiu;Ziyu Zhao;Qingguo Li;Dandong Luo
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文献类型：
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作者：
Zhimin Ma;Xuejuan Zhang;Lu Ping;Zicheng Zhong;Xiubing Zhang;Xiaodong Zhuang;Guanlin Wang;Qiupin Guo;Shaofeng Zhan;Zhenwen Qiu;Ziyu Zhao;Qingguo Li;Dandong Luo
超临界抗溶剂流化床包衣工艺（SAS-FB）作为一种制造干粉吸入器（DPI）的技术显示出巨大的潜力，该技术将纳米药物结合到微粉化基质颗粒上，利用了纳米颗粒和肺部输送的优点。在本研究中，柚皮苷（NAR）是一种具有低溶解度和体内降解问题的药理活性黄酮类化合物，被用作模型活性药物成分，通过 SAS-FB 构建基于纳米药物的 DPI。结果表明，加工后的 NAR 呈现出接近球形的形状和平均尺寸约为 130 nm 的无定形结构。值得注意的是，用不同流化基质制备的 SAS-FB 产品会导致不同的沉积模式，特别是当与粗乳糖混合以提高配方的细颗粒部分 (FPF) 时。 FPF与SAS-FB产品的比表面积呈正相关，而比表面积与表面粗糙度和颗粒尺寸直接相关。使用模拟肺液进行的体外溶出研究表明，产品上涂覆的 NAR 纳米颗粒在与溶液接触后立即释放，第一分钟内累积溶出超过 90%。重要的是，与口服原始 NAR 相比，优化的 DPI 制剂在 Sprague-Dawley 大鼠模型中表现出优越的体内血浆和肺 AUC0→∞ 分别为 51.33 倍和 104.07 倍。总体而言，SAS-FB 技术提供了一种生产纳米医学 DPI 产品的实用方法，该产品将纳米颗粒的优点与吸入微粒的空气动力学特性结合起来。
The supercritical antisolvent-fluidized bed coating process (SAS-FB) shows great potential as a technique to manufacture dry powder inhaler (DPI) that incorporate nanodrugs onto micronized matrix particles, capitalizing on the merits of both nanoparticle and pulmonary delivery. In this study, naringin (NAR), a pharmacologically active flavonoid with low solubility andin vivodegradation issues, was utilized as a model active pharmaceutical ingredient to construct nanomedicine-based DPI through SAS-FB. It is showed that processed NAR exhibited a near-spherical shape and an amorphous structure with an average size of around 130 nm. Notably, SAS-FB products prepared with different fluidized matrices resulted in varying deposition patterns, particularly when mixed with a coarse lactose to enhance the fine particle fraction (FPF) of the formulations. The FPF was positively associated with specific surface area of the SAS-FB products, while the specific surface area was directly related to surface roughness and particle size. In vitro dissolution studies using simulated lung fluid revealed that the NAR nanoparticles coated on the products were released immediately upon contact with solution, with a cumulative dissolution exceeding 90% within the first minute. Importantly, compared to oral raw NAR, the optimized DPI formulation demonstrated superiorin vivoplasmatic and pulmonary AUC0→∞by 51.33-fold and 104.07-fold respectively in a Sprague-Dawley rat model. Overall, SAS- FB technology provides a practical approach to produce nanomedicine DPI product that combine the benefits of nanoparticles with the aerodynamics properties of inhaled microparticles.