title: Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models.
abstract: Classically, the end point detection during fluid bed drying has been performed using indirect parameters, such as the product temperature or the humidity of the outlet drying air. This paper aims at comparing those classic methods to both in-line moisture and solid-state determination by means of Process Analytical Technology (PAT) tools (Raman and NIR spectroscopy) and a mass balance approach. The six-segmented fluid bed drying system being part of a fully continuous from-powder-to-tablet production line (ConsiGma™-25) was used for this study. A theophylline:lactose:PVP (30:67.5:2.5) blend was chosen as model formulation. For the development of the NIR-based moisture determination model, 15 calibration experiments in the fluid bed dryer were performed. Six test experiments were conducted afterwards, and the product was monitored in-line with NIR and Raman spectroscopy during drying. The results (drying endpoint and residual moisture) obtained via the NIR-based moisture determination model, the classical approach by means of indirect parameters and the mass balance model were then compared. Our conclusion is that the PAT-based method is most suited for use in a production set-up. Secondly, the different size fractions of the dried granules obtained during different experiments (fines, yield and oversized granules) were compared separately, revealing differences in both solid state of theophylline and moisture content between the different granule size fractions.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: Margot.Fonteyne@Ugent.be.
authors.forename: Margot
authors.initials: M
authors.lastname: Fonteyne
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gildemyn
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Peeters
authors.affiliation: BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Séverine Thérèse F C
authors.initials: ST
authors.lastname: Mortier
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercruysse
authors.affiliation: Department of Chemical and Biochemical Engineering, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Krist V
authors.initials: KV
authors.lastname: Gernaey
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Nopens
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: Thomas.DeBeer@Ugent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006813:Humidity; D007785:Lactose / Q000737:chemistry; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D011208:Powders / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013059:Spectrum Analysis, Raman / Q000379:methods; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013806:Theophylline / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D011145:Polyvinyls; D011208:Powders; D011759:Pyrrolidines; D013607:Tablets; C505150:poly(N-vinylpyrrolidine); D013806:Theophylline; D007785:Lactose
keywords: End-point detection; Fluid bed drying; Granule size fractions; NIR spectroscopy; PAT; Raman spectroscopy; Real-time monitoring