title: Application of terahertz pulse imaging as PAT tool for non-destructive evaluation of film-coated tablets under different manufacturing conditions.
abstract: Film-coated tablets (FCTs) are a popular solid dosage form in pharmaceutical industry. Manufacturing conditions during the film-coating process affect the properties of the film layer, which might result in critical quality problems. Here, we analyzed the properties of the film layer using a non-destructive approach with terahertz pulsed imaging (TPI). Hydrophilic tablets that become distended upon water absorption were used as core tablets and coated with film under different manufacturing conditions. TPI-derived parameters such as film thickness (FT), film surface reflectance (FSR), and interface density difference (IDD) between the film layer and core tablet were affected by manufacturing conditions and influenced critical quality attributes of FCTs. Relative standard deviation of FSR within tablets correlated well with surface roughness. Tensile strength could be predicted in a non-destructive manner using the multivariate regression equation to estimate the core tablet density by film layer density and IDD. The absolute value of IDD (Lateral) correlated with the risk of cracking on the lateral film layer when stored in a high-humidity environment. Further, in-process control was proposed for this value during the film-coating process, which will enable a feedback control system to be applied to process parameters and reduced risk of cracking without a stability test.
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Ozumi 180, 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 Bldg. 3F, 2-7-3 Kandata-cho, Chiyoda-ku, Tokyo 101-0046, Japan. Electronic address: masafumi.dohi@astellas.com.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Dohi
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Ozumi 180, Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Momose
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Ozumi 180, Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Ozumi 180, Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Ozumi 180, Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Ozumi 180, Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hakomori
authors.affiliation: Advantest Corporation, 48-2 Matsubara, Kamiayashi, Aoba-ku, Sendai, Miyagi 989-3124, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Sato
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 Bldg. 3F, 2-7-3 Kandata-cho, Chiyoda-ku, Tokyo 101-0046, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D005079:Excipients / Q000737:chemistry; D013499:Surface Properties; D013608:Tablets, Enteric-Coated / Q000592:standards*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013718:Tensile Strength; D055069:Terahertz Imaging / Q000379:methods*
chemical_list: D005079:Excipients; D013608:Tablets, Enteric-Coated
keywords: Crack defect; Film-coated tablet; Process analytical technology; Surface roughness; Tensile strength; Terahertz pulsed imaging