title: Evaluation of critical process parameters for inter-tablet coating uniformity of active-coated GITS using Terahertz Pulsed Imaging.
abstract: The aim of this study was the evaluation of critical process parameters (CPP) for inter-tablet coating uniformity in an active pan coating process using nondestructive Terahertz Pulsed Imaging (TPI). Coating uniformity was assessed by calculating the coefficient of variation (CV) of coating thickness measured by TPI, and the CV of API content measured by high performance liquid chromatography (HPLC). A design of experiments (DoE) was performed at pilot scale with drum load, drum speed, spray rate, run duration and spray pressure as factors. Good agreement in the CV of both analytical techniques was shown. The DoE models both revealed the same CPP: a low drum load, high drum speed, low spray rate and high run duration were beneficial for coating uniformity. The spray pressure was only significant in one of the DoE models. It was further shown that the negative impact of a high drum load on the CV cannot only be compensated by high drum speed, but also be compensated by a low spray rate and long run duration. It was demonstrated that TPI is a feasible tool for the measurement of inter-tablet coating uniformity and for the evaluation of CPP in an active pan coating process.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, University of Düsseldorf, Düsseldorf, Germany. Electronic address: daniela.brock@uni-duesseldorf.de.
authors.forename: Daniela
authors.initials: D
authors.lastname: Brock
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom. Electronic address: jaz22@cam.ac.uk.
authors.forename: J Axel
authors.initials: JA
authors.lastname: Zeitler
authors.affiliation: Global Chemical & Pharmaceutical Development, Bayer Pharma AG, Berlin, Germany. Electronic address: adrian.funke@bayer.com.
authors.forename: Adrian
authors.initials: A
authors.lastname: Funke
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, University of Düsseldorf, Düsseldorf, Germany. Electronic address: klaus.knop@uni-duesseldorf.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Knop
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, University of Düsseldorf, Düsseldorf, Germany. Electronic address: kleinebudde@uni-duesseldorf.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Kleinebudde
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D013607:Tablets
chemical_list: D013607:Tablets
keywords: Active coating; Candesartan cilexetil; Coating thickness; Content uniformity; Gastro-intestinal therapeutic system; HPLC; Inter-tablet coating uniformity; OROS; Pan coating; Terahertz Pulsed Imaging