Quantitative analysis of the layer separation risk in bilayer tablets using terahertz pulsed imaging

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• 作者：Masahiro Niwa ; Yasuhiro Hiraishi ; Norio Iwasaki ; Katsuhide Terada
• 关键词：TPI ; terahertz pulsed imaging ; SEM ; scanning electron microscopy ; XRCT ; X-ray computed tomography ; FDC ; fixed-dose combination ; NMR ; nuclear magnetic resonance ; API ; active pharmaceutical ingredient ; ANOVA ; analysis of variance
• 刊名：International Journal of Pharmaceutics
• 出版年：2013
• 出版时间：16 August, 2013
• 年：2013
• 卷：452
• 期：1-2
• 页码：249-256
• 全文大小：2169 K

文摘

Layer separation is a critical defect in many bilayer tablets. Despite its importance for product quality, few studies have investigated its root cause. We evaluated bilayer tablets with varying layer separation tendencies using terahertz pulsed imaging (TPI) in comparison with other analytical methods such as tensile strength measurements, friability testing, scanning electron microscopy (SEM), and X-ray computed tomography (XRCT). The layer separation risk was determined by friability testing and shown to be correlated with the final compression pressure used for bilayer tablet fabrication. TPI could nondestructively detect cracks between the component layers that lead to layer separation. The adhesion integrity of the interface was quantified by the interface index, a unique value derived from the time-domain terahertz waveform. The interface index showed good correlation to the layer separation tendency and could distinguish interface quality among seven batches of bilayer tablets. In contrast, SEM and XRCT detected structural defects but could not distinguish batches with high or low layer separation risk. TPI revealed the relationship between compression pressure and interface quality. Thus, TPI can aid in quality control by providing a precise estimate of the layer separation risk and robust quality of bilayer tablet development with better understanding of layer separation.