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

International Journal of Pharmaceutics, DOI: 10.1016/j.ijpharm.2013.05.010 May 2013

Authors: Masahiro Niwa^a,Yasuhiro Hiraishi^a, Norio Iwasaki^a, Katsuhide Terada^b
a Pharmaceutical Technology R&D Laboratories, CMC Center, Takeda Pharmaceutical Company Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan
b Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan

More details at: http://www.sciencedirect.com/science/article/pii/S0378517313004092

Highlights

• TPI could nondestructively detect cracks between the two layers.
• TPI could quantify adhesion integrity of bilayer tablet by interface index.
• Interface index showed good correlation to the layer separation tendency.
• TPI revealed the relationship between compression pressure and interface quality.

Abstract

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.

... 2.5. TPI. The TPI Imaga 2000 system (TeraView Ltd., Cambridge, UK) was used in this study. ... All data were acquired using the TPI Coating Scan software version 1.7.3 (TeraView) and analyzed using TPIcsView software version 2.3.4 (TeraView). 2.6. Statistical analysis. ...