基于LF-NMR/MRI的维C银翘片制粒中润湿剂评价方法研究

目的应用低场核磁共振时域技术(low field nuclear magnetic resonance time domain technique,LF-NMR)、低场核磁成像技术(low field nuclear magnetic resonance imaging,LF-MRI)对高剪切制粒中润湿剂(乙醇)进行定性、定量分析。方法以维C银翘片高剪切湿法制粒为研究对象,采用LF-NMR建立润湿剂用量测定方法,结合横向弛豫时间(T2)和LFMRI测得的二位影像图对润湿剂分布与变化进行定性分析,探讨峰面积(A₂)与颗粒得率的关系。结果润湿剂用量与A₂呈现良好的相关性(R²=0.9575)。随着润湿剂用量增加,T2向右移动,A₂逐渐增加,质子在增加;LF-MRI表明随着润湿剂用量增加,影像图逐渐清晰,即非结合态质子(束缚态质子及自由态质子)在颗粒中逐渐增加。当润湿剂用量增加至20%~25%时,结合态质子含量不再增加,此时颗粒得率最高。结论LF-NMR和LF-MRI能快速、准确检测制粒中润湿剂用量变化和分布状态,为阐明润湿剂对颗粒性质的影响和成型机制提供评价方法。

Evaluation of wetting agents in granulation of Vitamin C Yinqiao Tablets based on LF-NMR/MRI

Objective To qualitatively and quantitatively analyze the effects of low field nuclear magnetic resonance time domain technique (LF-NMR) and low field nuclear magnetic resonance imaging (LF-MRI) on wetting agents (alcohol) in high shear granulation. Methods Taking high shear wet granulation of Vitamin C Yinqiao Tablets (VCYT) as the research object, a method for determining the amount of wetting agent was established by using LF-NMR. The transverse relaxation time (T₂) measured by LF-NMR and the binary image obtained by LF-MRI were used to qualitatively analyze the distribution and variation of wetting agents. And the relationship between A₂ and particle yield was explored. Results There was good relationship between the amount of wetting agent and A₂ (R²=0.957 5). With the increase of the amount of wetting agent, T₂ moved to the right, A₂ gradually increased and the hydrogen proton was increased. LF-MRI showed that with the increase of the amount of wetting agent, the image was gradually clear, that was, un-bound hydrogen proton (irreducible hydrogen protons and free hydrogen protons) was gradually increased in the particles. When the wetting agent content increased to 20%-25%, the bound hydrogen proton content no longer increased, and the particle yield was the highest. Conclusion LF-NMR and LF-MRI can detect the content change and distribution of wetting agent in the granulation process quickly and accurately, which provides an evaluation method for clarifying the effect of wetting agent on particle properties and forming mechanism.