title: Quantitative analysis of the layer separation risk in bilayer tablets using terahertz pulsed imaging.
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.
authors.affiliation: Pharmaceutical Technology R&D Laboratories, CMC Center, Takeda Pharmaceutical Company Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan. masahiro.niwa@takeda.com
authors.forename: Masahiro
authors.initials: M
authors.lastname: Niwa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hiraishi
authors.forename: Norio
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011786:Quality Control; D013607:Tablets / Q000737:chemistry*; D013718:Tensile Strength; D055069:Terahertz Imaging; D014057:Tomography, X-Ray Computed
chemical_list: D013607:Tablets; D008353:Mannitol; D002482:Cellulose; C008079:hydroxypropylcellulose; D007785:Lactose