Michael Leitner

Non-destructive analysis of tablet coatings with optical coherence tomography.

Optical coherence tomography (OCT) is a non-invasive analysis technique allowing fast and high-quality cross-sectional imaging of scattering media. OCT is based on the physical phenomenon of low coherence interferometry and is thus well suited to image layered structures. In this paper, high-speed spectral domain OCT was used for the characterization of pharmaceutical tablet coatings, sampled at different stages of an industrial drum spray coating process, comprising tablets with a coating thickness ranging from uncoated to a target coating thickness of about 70 μm. In addition to the OCT investigation of layer thickness and homogeneity, tablet weight gain and tablet diameters were determined on a single-tablet level. Scanning electron microscopy (SEM) was applied for referencing the coating thickness obtained with OCT. We demonstrated that OCT allows rapid evaluation of coating properties, such as thickness and homogeneity independently from variations of the tablet core. In contrast to indirect methods, deviations observed with OCT can be related directly to the coating properties. Furthermore, for an extended morphological coating characterization, three dimensional images were reconstructed. Pending further developments, the high axial resolution and fast data acquisition rate of OCT has the potential for highly accurate, fast and low-cost coating control during and after manufacturing.

Optical coherence tomography as a novel tool for in-line monitoring of a pharmaceutical film-coating process

Optical coherence tomography (OCT) is a contact-free non-destructive high-resolution imaging technique based on low-coherence interferometry. This study investigates the application of spectral-domain OCT as an in-line quality control tool for monitoring pharmaceutical film-coated tablets. OCT images of several commercially-available film-coated tablets of different shapes, formulations and coating thicknesses were captured off-line using two OCT systems with centre wavelengths of 830nm and 1325nm. Based on the off-line image evaluation, another OCT system operating at a shorter wavelength was selected to study the feasibility of OCT as an in-line monitoring method. Since in spectral-domain OCT motion artefacts can occur as a result of the tablet or sensor head movement, a basic understanding of the relationship between the tablet speed and the motion effects is essential for correct quantifying and qualifying of the tablet coating. Experimental data was acquired by moving the sensor head of the OCT system across a static tablet bed. Although examining the homogeneity of the coating turned more difficult with increasing transverse speed of the tablets, the determination of the coating thickness was still highly accurate at a speed up to 0.7m/s. The presented OCT setup enables the investigation of the intra- and inter-tablet coating uniformity in-line during the coating process.

Automated pharmaceutical tablet coating layer evaluation of optical coherence tomography images

Film coating of pharmaceutical tablets is often applied to influence the drug release behaviour. The coating characteristics such as thickness and uniformity are critical quality parameters, which need to be precisely controlled. Optical coherence tomography (OCT) shows not only high potential for off-line quality control of film-coated tablets but also for in-line monitoring of coating processes. However, an in-line quality control tool must be able to determine coating thickness measurements automatically and in real-time. This study proposes an automatic thickness evaluation algorithm for bi-convex tables, which provides about 1000 thickness measurements within 1 s. Beside the segmentation of the coating layer, optical distortions due to refraction of the beam by the air/coating interface are corrected. Moreover, during in-line monitoring the tablets might be in oblique orientation, which needs to be considered in the algorithm design. Experiments were conducted where the tablet was rotated to specified angles. Manual and automatic thickness measurements were compared for varying coating thicknesses, angles of rotations, and beam displacements (i.e. lateral displacement between successive depth scans). The automatic thickness determination algorithm provides highly accurate results up to an angle of rotation of 30°. The computation time was reduced to 0.53 s for 700 thickness measurements by introducing feasibility constraints in the algorithm.

Optical Coherence Tomography – Applications in Non- Destructive Testing and Evaluation

The field of non-destructive testing and evaluation (NDTE) comprises many different techniques and approaches. Over the past few decades there have been tremendous ad‐ vances in NDTE technology, allowing researchers and engineers to tackle problems in many scientific and industrial fields. However, techniques enabling a fast, contactless, non-invasive, and high-resolution imaging of subsurface features at a level of only a few microns are still scarce.

Optical coherence tomography (OCT), space-resolved reflectance spectroscopy (SRS) and time-resolved reflectance spectroscopy (TRS): principles and applications to food microstructures

Abstract: This chapter presents the recent developments in advanced optical methods for exploring food microstructure. The chapter first discusses the basics of light propagation in food and the main limitations of classical approaches (e.g. continuous wave near infrared (NIR), colorimetry) for the measurement of the optical properties of food. It then describes the physical principles, the technological solutions and the advantages of optical coherence tomography, and of space- and time-resolved reflectance spectroscopy. The chapter includes examples of applications and an overview of future prospects.

Real-time data processing for in-line monitoring of a pharmaceutical coating process by optical coherence tomography

Coating of tablets is a widely applied unit operation in the pharmaceutical industry. Thickness and uniformity of the coating layer are crucial for efficacy as well as for compliance. Not only due to different initiatives it is thus essential to monitor and control the coating process in-line. Optical coherence tomography (OCT) was already shown in previous works to be a suitable candidate for in-line monitoring of coating processes. However, to utilize the full potential of the OCT technology an automatic evaluation of the OCT measurements is essential. The automatic evaluation is currently implemented in MATLAB and includes several steps: (1) extraction of features of each A-scan, (2) classification of Ascan measurements based on their features, (3) detection of interfaces (air/coating and coating/tablet core), (4) correction of distortions due to the curvature of the bi-convex tablets and the oblique orientation of the tablets, and (5) determining the coating thickness. The algorithm is tested on OCT data acquired by moving the sensor head of the OCT system across a static tablet bed. The coating thickness variations of single tablets (i.e., intra-tablet coating variability) can additionally be analyzed as OCT allows the measurement of the coating thickness on multiple displaced positions on one single tablet. Specifically, the information about those parameters emphasizes the high capability of the OCT technology to improve process understanding and to assure a high product quality.

Optical coherence tomography for non-destructive analysis of coatings in pharmaceutical tablets

Tablet coating is a common pharmaceutical technique to apply a thin continuous layer of solid on the top of a tablet or a granule containing active pharmaceutical ingredients (APIs). Coating thickness and homogeneity are critical parameters regarding the drug release rate, and consequently a direct or indirect monitoring strategy of these critical process parameters is essential. With the aid of Optical Coherence Tomography (OCT) it is not only possible to measure the absolute coating thickness, but also to detect inhomogeneities in the coating or substrate material. In this work the possible application of OCT as in-line method for monitoring pharmaceutical tablet film coating is studied. Firstly, the feasibility of OCT for analysis tablet coating is examined. Seven different commercially available film-coated tablets with different shapes, formulations and coating thicknesses were investigated off-line. OCT images were acquired by two different spectral-domain OCT systems operating at center wavelengths of 830 and 1325 nm. Since the images of both systems allow the analysis of the coatings, the OCT system employing the shorter wavelength and thus providing a higher axial resolution was selected for the further experiments. The influence of a moving tablet bed on OCT images was analyzed by considering a static tablet bed and moving the sensor head along the tablet bed. The ability to analyze the coating homogeneity is limited to a speed up to 0.3 m/s. However, determining the coating thickness and inter-coating uniformity is still possible up to a speed of 0.7 m/s.

Cutting Edge Technologies in Postharvest Research: Journey to the Centre of the Fruit

Food microstructure is at the base of many food quality roperties. The EU project InsideFood focuses on the pplication of high technological techniques to inspect internal quality of fruit. Tomographic techniques such as magnetic resonance imaging, X-ray computed tomography, optical coherence tomography and confocal microscopy can be used to obtain information about the 3-D microstructure of the fruit which is believed to affect quality attributes such as texture. Optical techniques such as spatially or time resolved reflectance spectroscopy may also be used to obtain information about fruit microstructure. This microstructural information can be incorporated in multiscale simulation models to predict the cellular gas concentrations in fruit. Such models aid towards a better understanding of, for instance, controlled atmosphere storage of apple and postharvest behaviour of fruits and vegetables in general.