Projects / Programmes
Complex hyperspectral system for automatic analysis and control of pharmaceutical pellet coating processes
| Code |
Science |
Field |
Subfield |
| 2.06.00 |
Engineering sciences and technologies |
Systems and cybernetics |
|
| Code |
Science |
Field |
| T111 |
Technological sciences |
Imaging, image processing |
| Code |
Science |
Field |
| 2.02 |
Engineering and Technology |
Electrical engineering, Electronic engineering, Information engineering |
ANG NIR hyperspectral imaging, image analysis, automatic quality inspection, process analytical technology, contactless pellet analysis
Researchers (21)
Organisations (4)
Abstract
Pharmaceutical pellets are made by agglomeration process in which fine particles are joined to improve content uniformity and flow characteristics, and to reduce segregation and dustiness. Additionally, pellets are typically coated with a thin film, serving as a protective layer against environmental factors, preventing the degradation of active pharmaceutical ingredients (API), controlling drug release rates, modifying color, masking taste, and defining the final size and shape of pellets. The highly important API release rates can be controlled by the volume-to-area ratios of pellets and with the compositions and thicknesses of the coating layers and/or composition of pellets matrix. Due to these advantages, coated pellets are increasingly replacing powder blends for filling pharmaceutical capsules and partially also in the process of pressing tablets. However, the highly complex multivariable pellet coating processes need to be controlled well to ensure high product yields and to prevent process failures, resulting in discarded batches and significant losses of revenues. For this purpose, a number of analytical methods are required for measuring the chemical (composition), physical (coating thickness) and geometrical (shape and size) properties of pellets. Currently, the average pellet size and coating thickness are commonly assessed off-line by microscopes or by dissolution tests, while the average chemical composition is usually verified by the HPLC (high performance liquid chromatography). Unfortunately, these methods are highly time consuming, retrospective, destructive, environment-harmful and provide no information on the spatial distributions of the pellet composition and film coating thickness, which both significantly affect the final therapeutical performance. Moreover, these classical methods are infeasible for real-time in-process pellet measurements, essential for effectively designing, controlling and optimizing the coating process and thereby assuring the high yield, quality and consistency of the final product – as stressed out in the PAT (Process Analytical Technology) initiative proposed by FDA (Food and Drug Administration) and EDA (European Drug Agency) as well. On the other hand, real-time statistical assessment of the average coating thickness can be achieved by the NIR (near infrared) point spectroscopy, while geometrical properties, such as size and shape, could be assessed by the analysis of NIR and visible hyper-spectral images, which can be acquired by the AOTF filters (acousto-optical tunable filters) or line-scan spectral cameras (see the attachment). However, in order to extract the geometrical, physical and chemical properties of pellets along with corresponding spatial distributions in real-time, new methods for automated analysis of spectra and hyper-spectral images need to be developed. In this manner we can achieve fast, efficient, reliable, noncontact, nondestructive, robust and environment friendly statistical analysis of pellets for reliable industrial process control.
In the proposed applied project, we will focus on the development of new methods for automatic, contactless and nondestructive real-time hyperspectral assessment of the geometrical, physical and chemical properties of pharmaceutical pellets. This will be performed by means of robust, automatic and real-time analysis of NIR and visible hyper-spectral images, especially focusing on assessing size, shape, composition, coating homogeneity and coating thickness of pellets. The development and integration of such methods will enable construction of innovative complex measurement systems and instruments, providing the means for efficiently designing, optimizing and controlling the production of pharmaceutical pellets and assessing the quality of pellets according to the PAT initiative, thereby assuring the quality and safety of medicines, increasing the productivity, and providing environment-friendly production.
Significance for science
The results of the research activities conducted during the applied project were disseminated in top-ranking scientific journals with high impact factors. Consequently, this will increase the visibility and reputation of Slovenia and in particular of the University of Ljubljana, as well as impact the long term development of technical and natural sciences in Slovenia. With respect to the nature of the applied project, we expect that the novel methods for in-line assessment of the most prominent pellet properties, such as the size and shape of pellets and the coating thickness and uniformity, will accelerate the transfer of top scientific knowledge to industry and stimulate novel research on the use of hyperspectral imaging technologies in the pharmaceutical production processes. As hyperspectral imaging is currently in the process of slowly but surely finding its way from the laboratory towards the pharmaceutical production processes, the conducted project also involved a fair share of basic research in the field of calibration and enhancement of acquired images and design of efficient illumination sources that are applicable to other fields of research, such as remote sensing, were hyperspectral imaging is considered an established imaging modality. Many of the findings will significantly affect future studies in the field of quality control by computer vision and enable substantial improvements of the existing imaging systems. In particular, extension of computer vision from the visible to the invisible part of the electromagnetic spectrum and the integration of multiple imaging modalities and spectral regions was shown to offer almost unlimited possibilities for the development of new technologies with high value added. Such systems will enable analysis, development and optimization of modern manufacturing processes and technologies in the pharmaceutical industry.
Significance for the country
The potentials of exploiting the results of the applied research project are numerous. The novel methods for real-time in-process assessment of the most prominent pelet properties will enable construction of modern high-tech control systems and instruments for simultaneous monitoring, understanding and optimization of pharmaceutical pellet coating processes, which will result in higher quality and safety of products, higher productivity and environment-friendly production. The prototype imaging system developed during the project presents a huge step towards efficient real-time in-process monitoring of the pharmaceutical coating processes. The results of the thorough evaluation based on multiple coating processes showed that the prototype imaging system and the novel image processing methods developed during the project, present a solid foundation for development of state-of-the-art systems suitable for application in full industrial scale coating processes. Besides, we expect that the novel methods for simultaneous calibration and resolution enhancement of hyperspectral images will promote addition research in the field. The image calibration and enhancement methods are of the utmost importance in industrial imaging systems, where high fidelity images are required for efficient and reliable real-time quantitative analysis of the acquired image. Moreover, the project has further strengthened the cooperation between the University of Ljubljana, Jožef Stefan Institute and Technology Park Ljubljana, in which the co-financing company Sensum, Computer Vision Systems resides. This scientific and technological cooperation has already led to the development of numerous high-tech computer vision products that are used for quality inspection and sorting of tablets and capsules in the pharmaceutical companies worldwide (see www.sensum.eu). The applied project further enhanced and extended the existing cooperation between the R&D institutions and enterprises and, thereby, significantly contributed to the transfer of top scientific knowledge to industry, which is essential for development of new high-tech products with high value added, accelerating the economic growth, and generating new well-paid jobs.
Most important scientific results
Annual report
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2012,
2013,
final report,
complete report on dLib.si
