Investigation of coating layer morphology by micro-computed X-ray tomography

Abstract Spray fluidized bed coating is a common process in food, chemical and pharmaceutical industry. Morphology of the formed layer is essential for product quality. Therefore, layer morphology was investigated in detail by X-ray micro-computed tomography (μ-CT) for porous γ-alumina particles coated with a solution of sodium benzoate with some hydroxypropyl-methylcellulose in water. Investigated properties are: layer thickness distribution on individual particles, porosity of the layer, and average layer thickness. The determination of layer thickness was performed in two different ways: (1) using two-dimensional cross-sections of volume images obtained from full μ-CT measurements, and (2) using single X-ray irradiation images without sample rotation. The porosity of the coating layer was evaluated from the volume images. Further studies were performed to investigate the influence of operating parameter, e.g. exposure time, on image quality and the obtained results. Special attention was put on ways to reduce the necessary measurement time while preserving the quality of the results. Finally, a new measurement protocol is presented which allows to measure coating thickness distributions in a particle population.

[1]  L. Chan,et al.  Comparative study of non-destructive methods to quantify thickness of tablet coatings. , 2010, International journal of pharmaceutics.

[2]  S. Šašić Determining the coating thickness of tablets by chiseling and image analysis. , 2010, International journal of pharmaceutics.

[3]  R. Reed,et al.  Rapid at-line analysis of coating thickness and uniformity on tablets using laser induced breakdown spectroscopy. , 2002, Journal of pharmaceutical and biomedical analysis.

[4]  H. Frijlink,et al.  Quantitative Image Analysis for Evaluating the Coating Thickness and Pore Distribution in Coated Small Particles , 2009, Pharmaceutical Research.

[5]  K. Dewettinck,et al.  Quantification of microparticle coating quality by confocal laser scanning microscopy (CLSM). , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[6]  Peter Kleinebudde,et al.  Validation of Terahertz coating thickness measurements using X-ray microtomography. , 2012, Molecular pharmaceutics.

[7]  H. Ohshima,et al.  Non-invasive and rapid analysis for observation of internal structure of press-coated tablet using X-ray computed tomography , 2009, Drug development and industrial pharmacy.

[8]  E. Tsotsas,et al.  Characterization of the internal morphology of agglomerates produced in a spray fluidized bed by X-ray tomography , 2012 .

[9]  Yaochun Shen,et al.  Non-destructive quantification of pharmaceutical tablet coatings using terahertz pulsed imaging and optical coherence tomography , 2011 .

[10]  J. Khinast,et al.  Non-destructive analysis of tablet coatings with optical coherence tomography. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[11]  J Axel Zeitler,et al.  In-vitro tomography and non-destructive imaging at depth of pharmaceutical solid dosage forms. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[12]  K. Morris,et al.  The effect of size and mass on the film thickness of beads coated in fluidized bed equipment , 1990 .

[13]  Bruno C. Hancock,et al.  X-ray microtomography of solid dosage forms , 2005 .

[14]  K. Wahlund,et al.  Analysis of film coating thickness and surface area of pharmaceutical pellets using fluorescence microscopy and image analysis. , 2000, Journal of pharmaceutical and biomedical analysis.

[15]  Andreas Bück,et al.  Influence of drying conditions on layer porosity in fluidized bed spray granulation , 2015 .

[16]  Gabriel I. Tardos,et al.  Use of X-ray tomography to study the porosity and morphology of granules , 2003 .

[17]  Bernd Rieger,et al.  X-ray micro tomography and image analysis as complementary methods for morphological characterization and coating thickness measurement of coated particles , 2010 .

[18]  J Axel Zeitler,et al.  Non-destructive evaluation of polymer coating structures on pharmaceutical pellets using full-field optical coherence tomography. , 2014, Journal of pharmaceutical sciences.

[19]  Andreas Bück,et al.  Continuous pellet coating in a Wurster fluidized bed process , 2013 .