Pellet Coating Thickness Determination by Near-Infrared Reflectance Spectroscopy: Comparison of Two Reference Methods

Abstract

The application of classical methods for pellet coating thickness determination (weight gain, microscopic analysis, dissolution testing) is time-consuming or does not consider pellets loss during the coating procedure. Therefore, these methods are not optimal for process control during pellets coating. The aim of this study was to develop rapid and valid methods for the determination of pellets average coating thickness by near infrared spectroscopy (NIRS). NIRS is not the primary method; therefore reference data are required for calibration. Data obtained from two reference methods for coating thickness determination (microscopic analysis, a geometric model calculated from pellets weight and density) were mutually compared. A geometric model was chosen as the simpler, quicker and more robust reference method. The polymer films studied were ethylcellulose (EC) and Eudragit® RS (ERS) applied on pellets in a Wurster column. The calibration models were carried out by partial least squares (PLS) regression, with two factors for EC and ERS films, respectively. The PLS validation sets had r > 0.97, and a standard error of validation, 3.29 μm (range tested 10 – 70 μm), for the EC film and 1.10 μm (range tested 2 – 20 μm) for the ERS film. The obtained results clearly demonstrate the feasibility of NIRS as a part of quality control procedure in the pharmaceutical industry. Keywords: Near-infrared spectroscopy, Pharmaceutical applications, Pellet coating, Coating thickness, Near-Infrared Reflectance Spectroscopy, pellets coating, NIRS, ethylcellulose, Eudragit, Wurster column, partial least squares (PLS) regression, colonic drug transport, Image Analysis, scanning electron microscopy, pellet sphericity, pycnometric density, Digital Micrometer, laser-induced breakdown spectroscopy, (terahertz pulsed imaging and Raman spectroscopy, X-ray powder diffractometry, interferometry technique, optical coherence tomography, refractive index, electromagnetic radiation, pan coating process, fluid bed process, small-scale rotating system, HPMC capsules, chemometric techniques, Principal component regression, partial least-squares regression, Microcrystalline cellulose, lactose monohydrate, diltiazem hydrochloride, polymethacrylate, CCD camera, FT-NIR Nicolet Antaris, TQ Analyst software, Mahalanobis distance