title: Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.
abstract: Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets.
authors.affiliation: Pharmaceutical Technology R&D Laboratories, CMC Center, Takeda Pharmaceutical Company Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan. Electronic address: masahiro.niwa@takeda.com.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Niwa
authors.affiliation: Pharmaceutical Technology R&D Laboratories, CMC Center, Takeda Pharmaceutical Company Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hiraishi
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011786:Quality Control; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013718:Tensile Strength; D055069:Terahertz Imaging
chemical_list: D005079:Excipients; D013607:Tablets; D008353:Mannitol; D002482:Cellulose; C109691:microcrystalline cellulose
keywords: ANOVA; Film-coated tablet; NIR; SEM; Scanning electron microscopy; Surface strength; TEFPS; TPI; Terahertz pulsed imaging; VDI; Visible surface defects; analysis of variance; near infrared spectroscopy; scanning electron microscopy; terahertz electric field peak strength; terahertz pulsed imaging; visible defect index