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结合太赫兹和光学相干断层扫描在线传感技术对制药锅包衣过程中片剂间包衣均匀性的测量

Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing.

作者信息

Lin Hungyen, Dong Yue, Markl Daniel, Williams Bryan M, Zheng Yalin, Shen Yaochun, Zeitler J Axel

机构信息

Department of Engineering, Lancaster University, Lancaster, UK.

Department of Electrical Engineering and Electronics, University of Liverpool, Liverpool, UK.

出版信息

J Pharm Sci. 2017 Apr;106(4):1075-1084. doi: 10.1016/j.xphs.2016.12.012. Epub 2016 Dec 23.

Abstract

We present in-line coating thickness measurements acquired simultaneously using 2 independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in situ during the film coating operation, and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 μm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 μm and is capable of measuring the intratablet coating uniformity and the intertablet coating thickness distribution within the coating pan. However, the OCT technique is less robust when it comes to the compatibility with excipients, dust, and potentially the maximum coating thickness that can be resolved. Using a custom-built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared with other process analytical technology sensors, such as near-infrared and Raman spectroscopy, the TPI and OCT sensors can resolve the intertablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining 2 complementary sensing modalities, it was possible to seamlessly monitor the coating process over the range of film thickness from 20 μm to greater than 250 μm.

摘要

我们展示了使用两种独立传感方式同时获取的在线涂层厚度测量结果

太赫兹脉冲成像(TPI)和光学相干断层扫描(OCT)。这两种技术都足够快速,能够在薄膜包衣操作过程中原位解析单个药片片剂的包衣厚度,并且这两种技术都是直接结构成像技术,不需要多变量校准。TPI传感器适用于测量大于50μm的涂层,即使在存在多种辅料且有颜料的情况下,也能穿透厚涂层。由于波长较长,太赫兹辐射不受包衣机内灰尘散射的影响。相比之下,OCT能够分辨薄至20μm的涂层,并且能够测量包衣锅内片剂内部的包衣均匀性和片剂间的包衣厚度分布。然而,在与辅料、灰尘的兼容性以及可分辨的最大包衣厚度方面,OCT技术的稳健性较差。使用定制的实验室规模包衣装置,在整个薄膜包衣操作过程中,TPI和OCT传感器独立获取包衣厚度测量结果。将在线TPI和OCT测量结果相互比较,并通过离线TPI和增重测量进行验证。与其他过程分析技术传感器(如近红外和拉曼光谱)相比,TPI和OCT传感器能够通过对过程中相当一部分片剂群体进行采样来解析片剂间的厚度分布。通过结合两种互补的传感方式,可以无缝监测从20μm到大于250μm的薄膜厚度范围内的包衣过程。

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