@article{MTMT:34771157, title = {Machine vision-based non-destructive dissolution prediction of meloxicam-containing tablets}, url = {https://m2.mtmt.hu/api/publication/34771157}, author = {Mészáros, Lilla Alexandra and Madarász, Lajos and Kádár, Szabina and Ficzere, Máté and Farkas, Attila and Nagy, Zsombor Kristóf}, doi = {10.1016/j.ijpharm.2024.124013}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {655}, unique-id = {34771157}, issn = {0378-5173}, abstract = {Machine vision systems have emerged for quality assessment of solid dosage forms in the pharmaceutical industry. These can offer a versatile tool for continuous manufacturing while supporting the framework of process analytical technology, quality-by-design, and real-time release testing. The aim of this work is to develop a digital UV/VIS imaging-based system for predicting the in vitro dissolution of meloxicam-containing tablets. The alteration of the dissolution profiles of the samples required different levels of the critical process parameters, including compression force, particle size and content of the API. These process parameters were predicted non-destructively by multivariate analysis of UV/VIS images taken from the tablets. The dissolution profile prediction was also executed using solely the image data and applying artificial neural networks. The prediction error (RMSE) of the dissolution profile points was less than 5%. The alteration of the API content directly affected the maximum concentrations observed at the end of the dissolution tests. This parameter was predicted with a relative error of less than 10% by PLS models that are based on the color components of UV and VIS images. In conclusion, this paper presents a modern, non-destructive PAT solution for real-time testing of the dissolution of tablets. © 2024 The Author(s)}, keywords = {meloxicam; Quality assessment; artificial neural network; Machine vision; Dissolution testing; Dissolution prediction}, year = {2024}, eissn = {1873-3476}, orcid-numbers = {Farkas, Attila/0000-0002-8877-2587} } @article{MTMT:33836337, title = {Novel manufacturing method for highly flexible poly(lactic acid) foams and ferroelectrets}, url = {https://m2.mtmt.hu/api/publication/33836337}, author = {Vadas, Dániel and Bordácsné Bocz, Katalin and Igricz, Tamás and Volk, János and Bordács, Sándor and Madarász, Lajos and Marosi, György}, doi = {10.1016/j.aiepr.2023.03.005}, journal-iso = {ADV INDUST ENGIN POLYMER RES}, journal = {ADVANCED INDUSTRIAL AND ENGINEERING POLYMER RESEARCH}, volume = {7}, unique-id = {33836337}, issn = {2542-5048}, abstract = {Poly (lactic acid) (PLA) foams have demonstrated a high variety of functional characteristics, still, the rigidity of this cellular material remains a major limiting factor when it comes to implementation options. In this contribution, PLA foams with outstanding flexibility were created for the first time by a new approach of uniaxial stretching and immediate relaxation following supercritical CO2-assisted extrusion foaming. Instead of improving the resilience of the PLA raw material, structural elasticity of the foam was achieved via altering the deformation mechanism from cell wall collapse or rupture towards reversible and extensive flexural strain. In addition, PLA foams with excellent piezoelectric properties were also achieved via high-voltage corona poling, giving additional function to the lens-like anisotropic foam cells. This foaming technology creates the opportunity to produce PLA piezoelectrets in a way entirely different from the state-of-the-art methods. Correlation between the tensile as well as compression elongations and moduli, cell morphology and longitudinal piezoelectric coefficients (d33) of electretized foam samples were studied. Unprecedented reversible tensile elongations of up to 16% and total elongations of up to 35% were reached, as well as considerable d33 values in the range of 50–320 pC/N were obtained for PLA ferroelectrets.}, year = {2024}, pages = {215-225}, orcid-numbers = {Volk, János/0000-0003-3633-6190; Bordács, Sándor/0000-0003-0420-5997; Marosi, György/0000-0002-4774-2023} } @article{MTMT:34085459, title = {Integrated continuous melt granulation-based powder-to-tablet line: Process investigation and scale-up on the same equipment}, url = {https://m2.mtmt.hu/api/publication/34085459}, author = {Záhonyi, Petra and Fekete, Daniel and Szabó, Edina and Madarász, Lajos and Fazekas, Arnika and Péter-Haraszti, Anna and Nagy, Zsombor Kristóf}, doi = {10.1016/j.ejpb.2023.06.005}, journal-iso = {EUR J PHARM BIOPHARM}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS}, volume = {189}, unique-id = {34085459}, issn = {0939-6411}, abstract = {In the last decades, continuous manufacturing (CM) has become a research priority in the pharmaceutical in-dustry. However, significantly fewer scientific researches address the investigation of integrated, continuous systems, a field that needs further exploration to facilitate the implementation of CM lines. This research outlines the development and optimization of an integrated, polyethylene glycol aided melt granulation-based powder-to-tablet line that operates fully continuously. The flowability and tabletability of a caffeine-containing powder mixture were improved through twin-screw melt granulation resulting in the production of tablets with improved breaking force (from 15 N to over 80 N), excellent friability, and immediate release dissolution. The system was also conveniently scaleable: the production speed could be increased from 0.5 kg/h to 8 kg/h with only minimal changes in the process parameters and using the same equipment. Thereby the frequent challenges of scale-up can be avoided, such as the need for new equipment and separate optimization.}, keywords = {continuous manufacturing; Melt granulation; Twin-screw granulation; Integrated continuous process}, year = {2023}, eissn = {1873-3441}, pages = {165-173}, orcid-numbers = {Szabó, Edina/0000-0001-9616-5122} } @article{MTMT:34004071, title = {AI-based analysis of in-line process endoscope images for real-time particle size measurement in a continuous pharmaceutical milling process}, url = {https://m2.mtmt.hu/api/publication/34004071}, author = {Madarász, Lajos and Mészáros, Lilla Alexandra and Köte, Á. and Farkas, Attila and Nagy, Zsombor Kristóf}, doi = {10.1016/j.ijpharm.2023.123060}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {641}, unique-id = {34004071}, issn = {0378-5173}, year = {2023}, eissn = {1873-3476}, orcid-numbers = {Farkas, Attila/0000-0002-8877-2587} } @article{MTMT:32918786, title = {Soft sensor for content prediction in an integrated continuous pharmaceutical formulation line based on the residence time distribution of unit operations}, url = {https://m2.mtmt.hu/api/publication/32918786}, author = {Gyürkés, Martin and Madarász, Lajos and Záhonyi, Petra and Köte, Ákos and Nagy, Brigitta and Pataki, Hajnalka and Nagy, Zsombor Kristóf and Domokos, András and Farkas, Attila}, doi = {10.1016/j.ijpharm.2022.121950}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {624}, unique-id = {32918786}, issn = {0378-5173}, abstract = {In this study, a concentration predicting soft sensor was achieved based on the Residence Time Distribution (RTD) of an integrated, three-step pharmaceutical formulation line. The RTD was investigated with color-based tracer experiments using image analysis. Twin-screw wet granulation (TSWG) was directly coupled with a horizontal fluid bed dryer and an oscillating mill. Based on integrated measurement, we proved that it is also possible to couple the unit operations in silico. Three surrogate tracers were produced with a coloring agent to investigate the separated unit operations and the solid and liquid inputs of the TSWG. The soft sensor’s prediction was compared to validating experiments of a 0.05 mg/g (15% of the nominal) concentration change with High-Performance Liquid Chromatography (HPLC) reference measurements of the active ingredient proving the adequacy of the soft sensor (RMSE < 4%).}, year = {2022}, eissn = {1873-3476}, orcid-numbers = {Domokos, András/0000-0003-1968-4679; Farkas, Attila/0000-0002-8877-2587} } @article{MTMT:32803411, title = {UV/VIS imaging-based PAT tool for drug particle size inspection in intact tablets supported by pattern recognition neural networks}, url = {https://m2.mtmt.hu/api/publication/32803411}, author = {Mészáros, Lilla Alexandra and Farkas, Attila and Madarász, Lajos and Bicsár, Rozália and Galata, Dorián László and Nagy, Brigitta and Nagy, Zsombor Kristóf}, doi = {10.1016/j.ijpharm.2022.121773}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {620}, unique-id = {32803411}, issn = {0378-5173}, year = {2022}, eissn = {1873-3476}, orcid-numbers = {Farkas, Attila/0000-0002-8877-2587} } @article{MTMT:32633240, title = {Real‐time amino acid and glucose monitoring system for the automatic control of nutrient feeding in CHO cell culture using raman spectroscopy}, url = {https://m2.mtmt.hu/api/publication/32633240}, author = {Domján, Júlia and Pantea, Eszter and Gyürkés, Martin and Madarász, Lajos and Kozák, Dóra and Farkas, Attila and Horváth, Balázs and Benkő, Zsuzsa and Nagy, Zsombor Kristóf and Marosi, György and Hirsch, Edit}, doi = {10.1002/biot.202100395}, journal-iso = {BIOTECHNOL J}, journal = {BIOTECHNOLOGY JOURNAL}, volume = {17}, unique-id = {32633240}, issn = {1860-6768}, abstract = {An innovative, Raman spectroscopy-based monitoring and control system is introduced in this paper for designing dynamic feeding strategies that allow the maintenance of key cellular nutrients at an ideal level in Chinese hamster ovary cell culture. The Partial Least Squares calibration models built for glucose, lactate and 16 (out of 20) individual amino acids had very good predictive power with low root mean square errors values and high square correlation coefficients. The developed models used for real-time measurement of nutrient and by-product concentrations allowed us to gain better insight into the metabolic behavior and nutritional consumption of cells. To establish a more beneficial nutritional environment for the cells, two types of dynamic feeding strategies were used to control the delivery of two-part multi-component feed media according to the prediction of Raman models (glucose or arginine). As a result, instead of high fluctuations, the nutrients (glucose together with amino acids) were maintained at the desired level providing a more balanced environment for the cells. Moreover, the use of amino acid-based feeding control enabled to prevent the excessive nutrient replenishment and was economically beneficial by significantly reducing the amount of supplied feed medium compared to the glucose-based dynamic fed culture.}, year = {2022}, eissn = {1860-7314}, orcid-numbers = {Farkas, Attila/0000-0002-8877-2587; Marosi, György/0000-0002-4774-2023} } @article{MTMT:32602243, title = {Powder filling of electrospun material in vials: A proof-of-concept study}, url = {https://m2.mtmt.hu/api/publication/32602243}, author = {Szabó, Edina and Záhonyi, Petra and Galata, Dorián László and Madarász, Lajos and Vass, Panna and Farkas, Attila and Dhondt, Jens and Andersen, Sune K. and Vígh, Tamás and Verreck, Geert and Csontos, István and Marosi, György and Nagy, Zsombor Kristóf}, doi = {10.1016/j.ijpharm.2021.121413}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {613}, unique-id = {32602243}, issn = {0378-5173}, abstract = {The present paper reports the powder filling of milled electrospun materials in vials, which contained voriconazole and sulfobutylether-β-cyclodextrin. High-speed electrospinning was used for the production of the fibrous sample, which was divided into 6 parts. Each portion was milled using different milling methods and sizes of sieves to investigate whether the milling influences the powder and filling properties. Bulk and tapped density tests, laser diffraction and angle of repose measurements were applied to characterize the milled powders, while a vibratory feeder was used for the feeding experiments. The correlation between the material property descriptors and the feeding responses was investigated by multivariate data analysis. Based on the results, three samples were chosen for the vial filling, which was accomplished with 3400 mg electrospun material containing 200 mg voriconazole, representative of the commercial product. The feed rate was set to fit the 240 g/h production rate of the electrospinning and the relative standard deviation of three repeated vial filling was determined to see the accuracy of the process. This research shows that by applying a suitable milling method it is possible to process electrospun fibers to a powder, which can be filled into vials and used as reconstitution dosage forms.}, year = {2022}, eissn = {1873-3476}, orcid-numbers = {Szabó, Edina/0000-0001-9616-5122; Vass, Panna/0000-0003-2206-565X; Farkas, Attila/0000-0002-8877-2587; Csontos, István/0000-0002-6858-1388; Marosi, György/0000-0002-4774-2023} } @article{MTMT:32601462, title = {Real-Time Monitoring of Continuous Pharmaceutical Mixed Suspension Mixed Product Removal Crystallization Using Image Analysis}, url = {https://m2.mtmt.hu/api/publication/32601462}, author = {Domokos, András and Madarász, Lajos and Stoffán, György Nimród and Tacsi, Kornélia and Galata, Dorián László and Csorba, Kristóf and Vass, Panna and Nagy, Zsombor Kristóf and Pataki, Hajnalka}, doi = {10.1021/acs.oprd.1c00372}, journal-iso = {ORG PROCESS RES DEV}, journal = {ORGANIC PROCESS RESEARCH & DEVELOPMENT}, volume = {26}, unique-id = {32601462}, issn = {1083-6160}, abstract = {In this work, we developed an in-line image analysis system for the monitoring of the continuous crystallization of an active pharmaceutical ingredient. Acetylsalicylic acid was crystallized in a mixed suspension mixed product removal crystallizer, which was equipped with overflow tubing as an outlet. A steep glass plate was placed under the outlet onto which the slurry dripped on its surface. The glass plate spread and guided the droplets toward the product collection filter. A high-speed process camera was mounted above the glass plate to capture images of the crystals. Several light sources were tested in various positions to find the appropriate experimental setup for the optimal image quality. Samples were taken during continuous operation for off-line particle size analysis in order to compare to the crystal size distributions calculated from the images. The results were in good agreement, and the trends of the process could be followed well using the images. As a next step, image analysis was operated throughout the entire continuous crystallization experiment, and a huge quantity of information was collected from the process. The crystal size distribution of the product was calculated every 30 s, which provided a thorough and detailed insight into the crystallization process.}, year = {2022}, eissn = {1520-586X}, pages = {149-158}, orcid-numbers = {Domokos, András/0000-0003-1968-4679; Vass, Panna/0000-0003-2206-565X} } @article{MTMT:32546925, title = {In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid process understanding and development}, url = {https://m2.mtmt.hu/api/publication/32546925}, author = {Madarász, Lajos and Köte, Á. and Hambalkó, Bence and Csorba, Kristóf and Kovács, V. and Lengyel, László and Marosi, György and Farkas, Attila and Nagy, Zsombor Kristóf and Domokos, András}, doi = {10.1016/j.ijpharm.2021.121280}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {612}, unique-id = {32546925}, issn = {0378-5173}, abstract = {The present paper serves as a demonstration how an in-line PAT tool can be used for rapid and efficient process development in a fully continuous powder to granule line consisting of an interconnected twin-screw wet granulator, vibrational fluid bed dryer, and a regranulating mill. A new method was investigated for the periodic in-line particle size measurement of high mass flow materials to obtain real-time particle size data of the regranulated product. The system utilises a vibratory feeder with periodically altered feeding intensity in order to temporarily reduce the mass flow of the material passing in front of the camera. This results in the drastic reduction of particle overlapping in the images, making image analysis a viable tool for the in-line particle size measurement of high mass-flow materials. To evaluate the performance of the imaging system, the effect of several milling settings and the liquid-to-solid ratio was investigated on the product's particle size in the span of a few hours. The particle sizes measured with the in-line system were in accordance with the expected trends as well as with the results of the off-line reference particle size measurements. Based on the results, the in-line imaging system can serve as a PAT tool to obtain valuable real-time information for rapid process development or quality assurance. © 2021 The Authors}, keywords = {process analytical technology (PAT); Dynamic Image Analysis (DIA); continuous pharmaceutical manufacturing; Twin-Screw Wet Granulation (TSWG); Vibrational Fluid Bed Drying}, year = {2022}, eissn = {1873-3476}, orcid-numbers = {Lengyel, László/0000-0002-5129-4198; Marosi, György/0000-0002-4774-2023; Farkas, Attila/0000-0002-8877-2587; Domokos, András/0000-0003-1968-4679} }