Taday等人发表了第一篇讨论Terahertz脉冲在制药部门中使用的论文。2003年(1)。本文表明,可以借助Terahertz脉冲光谱法鉴定出固体剂型的药物的多晶型物(图1)。Strachan等人报道了检测极限,表明可以在另一种多个混合物中测量一种多晶型物。(2)。由于大多数介电材料在光谱的Terahe亚博网站下载rtz区域都是透明的,因此很快就会意识到Terahertz脉冲可用于分析固体剂型的涂层厚度(3,4)。Unlike traditional microscopy measurements, the terahertz method provides the benefit of non-destructive assessment of coating thickness and other properties, preservingthe tablet for subsequent dissolution testing. This article outlines the techniques suitable for determining the coating thickness on tablets and correlating the thickness to wet dissolution.
Spencer等人进行了一项基于此的研究。(5)who measured the coating thickness of mesalamine tablets using terahertz pulsed imaging and was then able to correlate to tablet dissolution. In a series of papers, Lo et al.(6,7,8)demonstrated the possibility of correlating the coating thickness as well as the coating density. Additionally, the raw terahertz pulse and chemometrics were used by Lo et al. in later work to predict the dissolution of sustained release pharmaceutical product(9)。图2显示了肠上涂层片上的厚度与溶解度之间的相关性示例。直线上的外观是片剂涂料中存在的缺陷的结果。在最近的一篇论文中,May等人。证明了通过压缩测试测得的压碎力与使用一组在不同压缩力下压实的片剂测得的折射力与通过Terahertz脉冲成像测得的折射率,并且发现这是相关的TP片剂硬度(10)。同一组使用了涂料锅中的Terahertz传感器,跟随片剂在药品上的堆积(11)。
图1。磺基二唑(Spectra off Set)五个常见多晶型物的多晶型物
图2。肠涂层片的涂层厚度来自Terahertz脉冲测量值与不同涂层称重和聚合物水平(PEG)的平均溶解时间相关。黑点具有12%的钉子,而蓝点的固定液水平为9%。x = 4分钟时的utliner是由于片剂的涂层裂纹引起的。
测量
A TeraPulse 4000 with robot module (TeraView, Cambridge, UK) was used to perform the 3D TPI measurements (Figure 3). The operation of this system has been well described before by Zeilter et al.(4)。在点对点模式下获得的图像,步长为200 µm。
每个片剂对3000个测量进行了测量,每个片剂的测量值将近30分钟。图像是由Teraview的Terapulse数据分析软件拍摄的,不需要样品准备。源生成的Terahertz辐射可以将3毫米或更多的样品穿透到样品中。
每当由于片剂的化学特征或物理特征变化而导致折射率变化时,就会发生反思(图4)
这是一种弹道反射,发生在药品内界面的表面上,并且由于在不同时间发生的光速有限。
It is possible to use the time-of-flight capabilities of the technique to distinguish between pulses coming from different boundaries in the sample and randomly scattered photons.
也可以通过测量在不同时间到达的脉冲之间的差异来获得剂型涂层厚度的地图 - 可以为产品内的多个表面和顶部表面进行多个表面。可以使用机器人系统在三个维度上检查平板电脑。图5显示了涂料混合物中有固体负荷的10%和16%的体重增加肠涂层片之间的差异。相同的颜色尺度用于绘制片剂上的涂料厚度。
Application Area
- Fault analysis of coating on production batches
- 双层产品的产品开发
- 增强固体剂型上涂料的性能
- The system has been used to solve production problems with polymer coatings and also in product development
图3。Schematic diagram a TeraPulse 4000 with robotic system used to measure tablets.
Figure 4.从Terahertz脉冲成像法获得的数据示例
Figure 5.涂层的片剂示例在涂料中涂有10%和16%的体重增加和不同的固体负载。图像用红色250微米和深蓝色50微米绘制在相同的颜色尺度上。
References
- Taday PF,Bradley IV,Arnone DD,PepperM。“使用Terahertz脉冲光谱研究药物的晶体结构:盐酸Ranitidine盐酸盐多晶型物的案例研究” J Pharm Sci。92(4):831-8(2003)
- C.J. Strachan P. F. Taday,D。A. Newnham,K。C. Gordon,J。A. Zeitler,M。Pepper,T。Rades“使用Terahertz脉冲光谱量来量化药物多态性和结晶性”,J。Pharmaceutical Sciences,94(4),837-846(2005),亚博老虎机网登录
- AJ。Fitzgerald,Be Cole和Pf Taday,“使用Terahertz脉冲成像对片剂涂料厚度的无损分析”,J Pharm Sci。94(1):177-83(2005)。
- Zeitler JA,Shen Y,Baker C,Taday PF,Pepper M,Rades T“通过三维Terahertz脉冲成像分析固体口服剂型的涂层结构和界面”,J Pharm Sci。96(2):330-40(2007)。
- John A. Spencer, Zongming Gao, Terry Moore, Lucinda F. Buhse, Philip Taday, David A. Newnham, Yaochun Shen, Alessia Portieri, Ajaz Husain, “Delayed Release Tablet Dissolution Related to Coating Thickness by Terahertz Pulsed Image Mapping” J. Pharmaceutical Science 97(4), 1543-1550 (2008).
- Ho L, Müller R, Römer M, Gordon KC, Heinämäki J, Kleinebudde P, Pepper M, Rades T, Shen YC, Strachan CJ, Taday PF, Zeitler JA., “Analysis of sustained-release tablet film coats using terahertz pulsed imaging”, J Control Release. 119(3):253-61 (2007).
- Ho L, Müller R, Gordon KC, Kleinebudde P, Pepper M, Rades T, Shen Y, Taday PF, Zeitler JA, “Terahertz pulsed imaging as an analytical tool for sustained-release tablet film coating”, Eur J Pharm Biopharm. 71(1):117-23 (2009).
- Ho L,MüllerR,Gordon KC,Kleinebudde P,Pepper M,Rades T,Shen Y,Taday PF,Zeitler JA“监测膜涂层操作并使用Terahertz Pulsed Imaging进行药物溶解”):4866-76(2009)。
- Ho L, Müller R, Gordon KC, Kleinebudde P, Pepper M, Rades T, Shen Y, Taday PF, Zeitler JA “Applications of terahertz pulsed imaging to sustained-release tablet film coating quality assessment and dissolution performance” J Control Release. 127(1):79-87 (2008).
- Robert K. May, Ke Su, Lianghao Han, Shuncong Zhong, James A. Elliott, Lynn F. Gladden, Mike Evans, Yaochun Shen, J. Axel Zeitler J “Hardness and Density Distributions of Pharmaceutical Tablets Measured by Terahertz Pulsed Imaging” J. Pharm Sci 102:2179–2186 (2013)
- May RK,Evans MJ,Zhong S,Warr I,Gladden LF,Shen Y,Zeitler JA,“ Terahertz在线传感器,用于实时胶片涂层期间单个平板电脑的直接涂层厚度测量” J Pharm Sci。2010年10月18日doi:10.1002/jps.22359
此信息已从Teraview Ltd提供的材料中采购,审查和改编。亚博网站下载
有关此消息来源的更多信息,请访问Teraview Ltd.