Evaluation of critical process parameters for inter-tablet coating uniformity of active-coated GITS using Terahertz Pulsed Imaging

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 88; no. 2; pp. 434 - 442
• Main Authors: Brock, Daniela, Axel Zeitler, J., Funke, Adrian, Knop, Klaus, Kleinebudde, Peter
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2014
• Subjects: Active coating; Candesartan cilexetil; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Coating thickness; Content uniformity; Gastro-intestinal therapeutic system; HPLC; Inter-tablet coating uniformity; OROS; Pan coating; Tablets; Terahertz Pulsed Imaging; Inter-tablet coating uniformity; Candesartan cilexetil; OROS; Content uniformity; Pan coating; Coating thickness; Gastro-intestinal therapeutic system; Active coating; Terahertz Pulsed Imaging; HPLC
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2014.06.016

[Display omitted] •We investigated coating thickness uniformity using Terahertz Pulsed Imaging.•High correlation between coating thickness uniformity and content uniformity was found.•Critical process parameters for coating uniformity were successfully evaluated. 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.