title: Application of Terahertz Attenuated Total Reflection Spectroscopy to Detect Changes in the Physical Properties of Lactose during the Lubrication Process Required for Drug Formulation.
abstract: Manufacturing the solid dosage form of an orally administered drug requires lubrication to enhance manufacturability, ensuring that critical quality attributes such as disintegration and dissolution of the drug product are maintained during manufacture. Here, to evaluate lubrication performance during manufacture, we used terahertz attenuated total reflection (THz-ATR) spectroscopy to detect differences in the physical characteristics of the lubricated powder. We applied a simple formulation prepared by blending granulated lactose as filler with magnesium stearate as lubricant. A flat tablet was prepared using the lubricated powder to acquire sharp THz-ATR absorption peaks of the samples. First, we investigated the effects of lubricant concentration and compression pressure on preparation of the tablet and then determined the effect of the pressure applied to samples in contact with the ATR prism on sample absorption amplitude. We focused on the differences in the magnitudes of spectra at the lactose-specific frequency. Second, we conducted the dynamic lubrication process using a 120-L mixer to investigate differences in the magnitudes of absorption corresponding to the lactose-specific frequency during lubrication. In both studies, enriching the lubricated powder with a higher concentration of magnesium stearate or prolonging blending time correlated with higher magnitudes of spectra at the lactose-specific frequency. Further, in the dynamic lubrication study, the wettability and disintegration time of the tablets were compared with the absorption spectra amplitudes at the lactose-specific frequency. We conclude that THz-ATR spectroscopy is useful for detecting differences in densities caused by a change in the physical properties of lactose during lubrication.
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Dohi
authors.forename: Wataru
authors.initials: W
authors.lastname: Momose
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamashita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hakomori
authors.forename: Shusaku
authors.initials: S
authors.lastname: Sato
authors.forename: Shuji
authors.initials: S
authors.lastname: Noguchi
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D004339:Drug Compounding / Q000379:methods*; D007785:Lactose / Q000737:chemistry*; D008153:Lubrication; D011312:Pressure; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013607:Tablets / Q000737:chemistry; D055068:Terahertz Spectroscopy; D013997:Time Factors
chemical_list: D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid; D007785:Lactose