X-ray micro tomography and image analysis as complementary methods for morphological characterization and coating thickness measurement of coated particles

Abstract

This work demonstrates the potentiality of X-ray micro tomography as a powerful tool for morphological characterization of coated particles and, in particular, of their coating layer. X-ray micro tomography provides a high level of details at both micro and macro-scale. It was, in this work, used in the determination of density, porosity, surface/volume ratio, and thickness of the coating layer. Special emphasis was put on evaluation of the adhesion core/coating shell due to its strong influence on the acceptance and goodness of the final coated compound. Different definitions of coating thickness are evaluated. The variance of these properties is assessed within particles and between particles. A novel protocol was developed in order to segment the coating shell out from the core particles. The segmented out images were used to create 3D models of such coating shells. General aspects of theses models are discussed. The potential and limitations of X-ray micro tomography are finally highlighted based on the experimental work. Image analysis was used to determine the coating thickness applied on the core particles as complementary and reference method. As case study, two series of coated particles, prepared using top-spray fluidized bed coater, were obtained, each one employing three standard well-know coating agents.

Introduction

Aqueous film coating is a process commonly employed in the food and pharmaceutical industries. Agglomerates, granules, tablets, pellets and nonpareil seeds are often coated with polymers in order to control the dissolution of drug from the dosage form to give the product specific functionalities. Microencapsulation is a very popular method for the preparation of coated particles and, in general, for controlled release systems. Since small changes in processing parameters have the potential to greatly affect the properties of the final product, a rapid and non-destructive analytical method which detects these differences and gives an indication of the final product characteristics could be employed profitably as a quality control tool. Examples of these characteristics are: the thickness of the coating applied and the surface area of the coating shell [1], [2], intra and inter-coating thickness uniformity and homogeneity [3], adhesion core-coating shell [4], [5] and micro-level structure of the coating layer (e.g. porosity, micro-cracks, air bubbles). For many reasons it is of interest to assess the above mentioned parameters and to confirm non-ambiguously the quality of the both coating process and coating shell. In fact, evaluating the properties of coatings has the double purpose of assessing the adequacy of the process controls and ensuring the optimal performance of the final product.

Several techniques are currently available for coating analyses which provide the spatial resolution necessary for thin coating layer uniformity and structure measurements as well as prediction of coating thickness.

The most widely used techniques to visualize coated particles, coating structure and thickness, surface morphology are conventional light microscopy (LM) and scanning electron microscopy (SEM) [6], [7], [8]. Among several applications, Atomic Force Microscopy (AFM) studies surface roughness. Other methods are near-infrared (near-IR) spectroscopy [1], [9], [10], [11] and laser profilometer [12] that are fast and highly accurate. Alternatively, a technique that potentially can be used for routine in-process testing of coatings is Laser Induced Breakdown Spectroscopy (LIBS), which has the potential to provide both rapid in-line analyses of multiple samples as well as the necessary spatial resolution [13]. X-ray photoelectron spectroscopy (XPS) is a powerful technique widely used for the surface analysis of materials mainly, but it has also been used for coating thickness estimation [14]. Confocal scanning laser microscopy (CLSM) [15], [16], [17], [18], [19], [20], [21] minimizes scattered light from out-of-focus structures, and permits, through use of different fluorescence labels [22], not only analysis on the surface but also inside the material [23].

X-ray micro tomography is a relative new technique developed in the late 1970s, which enables the non-destructive, three-dimensional, visualization of the internal structure of objects [24], [25]. It is based on the interaction of X-rays with matter. When X-rays pass through an object they will be attenuated in a way depending on the density and the atomic number of the object under investigation and of the used X-ray energies. By using projection images obtained from different angles a reconstruction can be made of a virtual slice through the object, non-destructively. By implementing mathematical algorithms, X-ray micro tomography creates cross-sectional images of the internal structure of the object. When these different consecutive slices are reconstructed a 3D visualization can be obtained with high resolution.

The objective of this study was to demonstrate the feasibility of X-ray micro tomography to successfully quantify film coating quality and to show the capability of this technique for measuring the thickness, its uniformity, the porosity, the density, the volume and the surface of a polymeric coating on not-spherical core particles. Particular attention was put on the valuation of the internal structures of coating layer as well as the interface core-coating shell. First a theoretical description of the technique is presented then its performance will be illustrated by both the quantification of coating quality and the calculation of coating thickness of coated particles produced via top-spray fluidised bed coating. The particles were coated by aqueous solutions of three different polymer materials and three coating levels. Two types of core particles were used. The present work aims also to demonstrate the simplicity and speed of this procedure as well as the value of the additional information that could be obtained by simple analysis.