Yang Le, Wu Sijun, Qu Haibin
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
AAPS PharmSciTech. 2025 Aug 20;26(7):216. doi: 10.1208/s12249-025-03213-5.
This study explored the application of Micro-Flow Imaging (MFI) technology in detecting insoluble particles in traditional Chinese medicine (TCM) injections. Using Danshen Injection (DI) and Guanxinning Injection (GXNI) as examples, we verified the advantages of the MFI method in detecting particle size, morphology, and concentration. Compared to the Light Obscuration (LO) method, MFI captured particles more accurately in the size ranges of ≥ 2 μm, ≥ 5 μm, ≥ 10 μm, and ≥ 25 μm, detecting 5-13 × more particles in the ≥ 10 μm range, especially when detecting semi-transparent non-protein particles. Additionally, the clarity grades assigned by experienced analysts through visual inspection strongly correlated with overall particle concentration (≥ 2 μm), supporting the hypothesis that sub-visible particles (SVPs, particles smaller than 50 μm that are not visible to the naked eye) could reflect the likelihood of visible particles, thus enabling the quantitative characterization of clarity. Morphological analysis showed that endogenous particles in both injections underwent significant changes in shape and intensity during growth, mainly driven by transparent particles, which became increasingly elongated or elliptical in shape. These findings demonstrate that the MFI method offers clear advantages in detecting insoluble particles and quantifying clarity, providing both detailed quantitative data and qualitative information to support particle traceability. Despite challenges in standardization and regulatory acceptance, MFI represents a powerful tool for in-depth research on insoluble particle formation in TCM injections.
本研究探讨了微流成像（MFI）技术在检测中药注射剂中不溶性颗粒方面的应用。以丹参注射液（DI）和冠心宁注射液（GXNI）为例，我们验证了MFI方法在检测颗粒大小、形态和浓度方面的优势。与光阻法（LO）相比，MFI在≥2μm、≥5μm、≥10μm和≥25μm的尺寸范围内能更准确地捕获颗粒，在≥10μm范围内检测到的颗粒数量多出5 - 13倍，尤其是在检测半透明非蛋白质颗粒时。此外，经验丰富的分析人员通过目视检查给出的澄清度等级与总体颗粒浓度（≥2μm）密切相关，支持了亚可见颗粒（SVPs，即小于50μm肉眼不可见的颗粒）能够反映可见颗粒可能性的假设，从而实现了澄清度的定量表征。形态分析表明，两种注射液中的内源性颗粒在生长过程中形状和强度发生了显著变化，主要由透明颗粒驱动，这些透明颗粒形状越来越细长或呈椭圆形。这些发现表明，MFI方法在检测不溶性颗粒和定量澄清度方面具有明显优势，提供了详细的定量数据和定性信息以支持颗粒溯源。尽管在标准化和监管认可方面存在挑战，但MFI仍是深入研究中药注射剂中不溶性颗粒形成的有力工具。
