Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom.
J Magn Reson. 2012 Mar;216:183-91. doi: 10.1016/j.jmr.2012.01.021. Epub 2012 Feb 8.
A quantitative PGSE-RARE pulse sequence was developed and successfully applied to the in situ dissolution of two pharmaceutical formulations dissolving over a range of timescales. The new technique was chosen over other existing fast velocity imaging techniques because it is T(2) weighted, not T(2)(∗) weighted, and is, therefore, robust for imaging time-varying interfaces and flow in magnetically heterogeneous systems. The complex signal was preserved intact by separating odd and even echoes to obtain two phase maps which are then averaged in post-processing. Initially, the validity of the technique was shown when imaging laminar flow in a pipe. Subsequently, the dissolution of two drugs was followed in situ, where the technique enables the imaging and quantification of changes in the form of the tablet and the flow field surrounding it at high spatial and temporal resolution. First, the complete 3D velocity field around an eroding salicylic acid tablet was acquired at a resolution of 98×49 μm(2), within 20 min, and monitored over ∼13 h. The tablet was observed to experience a heterogeneous flow field and, hence a heterogeneous shear field, which resulted in the non-symmetric erosion of the tablet. Second, the dissolution of a fast dissolving immediate release tablet was followed using one-shot 2D velocity images acquired every 5.2 s at a resolution of 390×390 μm(2). The quantitative nature of the technique and fast acquisition times provided invaluable information on the dissolution behaviour of this tablet, which had not been attainable previously with conventional quantitative MRI techniques.
我们开发了一种定量 PGSE-RARE 脉冲序列,并成功地将其应用于两种在不同时间尺度内溶解的药物制剂的原位溶解研究。之所以选择这种新技术而不是其他现有的快速速度成像技术,是因为它是 T(2)加权的,而不是 T(2)(∗)加权的,因此对于成像随时间变化的界面和磁不均匀系统中的流动非常稳健。通过分离奇数和偶数回波来保留复杂信号的完整性,以获得两个相位图,然后在后期处理中对其进行平均。首先,在管道中进行层流成像时证明了该技术的有效性。随后,我们对两种药物的原位溶解进行了跟踪,该技术能够以高空间和时间分辨率对片剂的形态和周围流场的变化进行成像和定量。首先,在 20 分钟内以 98×49μm(2)的分辨率获取了正在侵蚀的水杨酸片剂周围完整的 3D 速度场,并监测了约 13 小时。观察到片剂经历了不均匀的流场,因此也经历了不均匀的剪切场,这导致了片剂的非对称侵蚀。其次,使用分辨率为 390×390μm(2)的单次 2D 速度图像,每 5.2 秒采集一次,对快速溶解的即释片剂的溶解进行了跟踪。该技术的定量性质和快速采集时间为该片剂的溶解行为提供了非常有价值的信息,这是以前使用常规定量 MRI 技术无法实现的。