title: Applying terahertz technology for nondestructive detection of crack initiation in a film-coated layer on a swelling tablet.
abstract: Here, we describe a nondestructive approach using terahertz wave to detect crack initiation in a film-coated layer on a drug tablet. During scale-up and scale-down of the film coating process, differences in film density and gaps between the film-coated layer and the uncoated tablet were generated due to differences in film coating process parameters, such as the tablet-filling rate in the coating machine, spray pressure, and gas-liquid ratio etc. Tablets using the PEO/PEG formulation were employed as uncoated tablets. We found that heat and humidity caused tablets to swell, thereby breaking the film-coated layer. Using our novel approach with terahertz wave nondestructively detect film surface density (FSD) and interface density differences (IDDs) between the film-coated layer and an uncoated tablet. We also found that a reduced FSD and IDD between the film-coated layer and uncoated tablet increased the risk of crack initiation in the film-coated layer, thereby enabling us to nondestructively predict initiation of cracks in the film-coated layer. Using this method, crack initiation can be nondestructively assessed in swelling tablets after the film coating process without conducting accelerated stability tests, and film coating process parameters during scale-up and scale-down studies can be appropriately established.
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan ; Faculty of Pharmaceutical Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan ; PAT Committee, Japan Society of Pharmaceutical Machinery and Engineering, Miyoshi Bld. 3F, 2-7-3 Kandata-cho, Chiyoda-ku, Tokyo 101-0046, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Momose
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Katakawa
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Imai
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sako
authors.affiliation: Advantest Corporation, 48-2 Matsubara, Kamiayashi, Aoba-ku, Sendai, Miyagi 989-3124, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kato
authors.affiliation: Advantest Corporation, 48-2 Matsubara, Kamiayashi, Aoba-ku, Sendai, Miyagi 989-3124, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Irisawa
authors.affiliation: Faculty of Pharmaceutical Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan ; PAT Committee, Japan Society of Pharmaceutical Machinery and Engineering, Miyoshi Bld. 3F, 2-7-3 Kandata-cho, Chiyoda-ku, Tokyo 101-0046, Japan.
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
authors.affiliation: Faculty of Pharmaceutical Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan ; PAT Committee, Japan Society of Pharmaceutical Machinery and Engineering, Miyoshi Bld. 3F, 2-7-3 Kandata-cho, Chiyoda-ku, Tokyo 101-0046, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
keywords: Coating; Process analytical technology; Quality by design; Spectroscopy; Swelling; Terahertz