TY - JOUR AU - Mészáros, Lilla Alexandra AU - Madarász, Lajos AU - Kádár, Szabina AU - Ficzere, Máté AU - Farkas, Attila AU - Nagy, Zsombor Kristóf TI - Machine vision-based non-destructive dissolution prediction of meloxicam-containing tablets JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 655 PY - 2024 PG - 13 SN - 0378-5173 DO - 10.1016/j.ijpharm.2024.124013 UR - https://m2.mtmt.hu/api/publication/34771157 ID - 34771157 N1 - Export Date: 5 April 2024 CODEN: IJPHD Correspondence Address: Kristóf Nagy, Z.; Department of Organic Chemistry and Technology, Műegyetem rakpart 3, Hungary; email: zsknagy@oct.bme.hu AB - 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) LA - English DB - MTMT ER - TY - JOUR AU - Vadas, Dániel AU - Bordácsné Bocz, Katalin AU - Igricz, Tamás AU - Volk, János AU - Bordács, Sándor AU - Madarász, Lajos AU - Marosi, György TI - Novel manufacturing method for highly flexible poly(lactic acid) foams and ferroelectrets JF - ADVANCED INDUSTRIAL AND ENGINEERING POLYMER RESEARCH J2 - ADV INDUST ENGIN POLYMER RES VL - 7 PY - 2024 IS - 2 SP - 215 EP - 225 PG - 11 SN - 2542-5048 DO - 10.1016/j.aiepr.2023.03.005 UR - https://m2.mtmt.hu/api/publication/33836337 ID - 33836337 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Záhonyi, Petra AU - Fekete, Daniel AU - Szabó, Edina AU - Madarász, Lajos AU - Fazekas, Arnika AU - Péter-Haraszti, Anna AU - Nagy, Zsombor Kristóf TI - Integrated continuous melt granulation-based powder-to-tablet line: Process investigation and scale-up on the same equipment JF - EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS J2 - EUR J PHARM BIOPHARM VL - 189 PY - 2023 SP - 165 EP - 173 PG - 9 SN - 0939-6411 DO - 10.1016/j.ejpb.2023.06.005 UR - https://m2.mtmt.hu/api/publication/34085459 ID - 34085459 N1 - Funding Agency and Grant Number: Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund [FK- 132133]; Ministry of Innovation and Technology of Hungary [FK- 132133]; Gedeon Richter Talentum Foundation; New National Excellence Program of the Ministry of Human Capacities [UNKP-22-3-I-BME- 182, UNKP-22-5-BME-301]; Janos Bolyai Research Scholarship of the Hungarian Academy of Science [TKP-9-8/PALY-2021] Funding text: The research has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the [FK- 132133] funding scheme. The scientific research publicized in this article was reached with the sponsorship of Gedeon Richter Talentum Foundation in framework of Gedeon Richter Excellence PhD Scholarship of Gedeon Richter. This project was supported by the UNKP-22-3-I-BME- 182 and UNKP-22-5-BME-301 New National Excellence Program of the Ministry of Human Capacities. This paper was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Science. Project no. TKP-9-8/PALY-2021 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Madarász, Lajos AU - Mészáros, Lilla Alexandra AU - Köte, Á. AU - Farkas, Attila AU - Nagy, Zsombor Kristóf TI - AI-based analysis of in-line process endoscope images for real-time particle size measurement in a continuous pharmaceutical milling process JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 641 PY - 2023 SN - 0378-5173 DO - 10.1016/j.ijpharm.2023.123060 UR - https://m2.mtmt.hu/api/publication/34004071 ID - 34004071 N1 - Export Date: 27 February 2024 CODEN: IJPHD Correspondence Address: Nagy, Z.K.; Department of Organic Chemistry and Technology, H-1111, Budapest, Műegyetem rakpart 3, Hungary; email: zsknagy@oct.bme.hu Chemicals/CAS: sodium chloride, 7647-14-5, 23724-87-0, 49658-21-1; Excipients; Sodium Chloride Funding details: Mesterséges Intelligencia Nemzeti Laboratórium, MILAB Funding details: European Commission, EC, RRF-2.3.1-21-2022-00004 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: Supported by the ÚNKP-22-3-II-BME-154 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. Supported by the the European Union project RRF-2.3.1-21-2022-00004 within the framework of the Artificial Intelligence National Laboratory LA - English DB - MTMT ER - TY - JOUR AU - Gyürkés, Martin AU - Madarász, Lajos AU - Záhonyi, Petra AU - Köte, Ákos AU - Nagy, Brigitta AU - Pataki, Hajnalka AU - Nagy, Zsombor Kristóf AU - Domokos, András AU - Farkas, Attila TI - Soft sensor for content prediction in an integrated continuous pharmaceutical formulation line based on the residence time distribution of unit operations JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 624 PY - 2022 PG - 12 SN - 0378-5173 DO - 10.1016/j.ijpharm.2022.121950 UR - https://m2.mtmt.hu/api/publication/32918786 ID - 32918786 N1 - Export Date: 15 July 2022 CODEN: IJPHD Funding details: Hungarian Scientific Research Fund, OTKA, FK-132133, ÚNKP-21-3-II-BME-309, ÚNKP-21-4-I-BME-329 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: Innovációs és Technológiai Minisztérium Funding text 1: A. Farkas acknowledges the financial support received through the PREMIUM post-doctorate research program of the Hungarian Academy of Sciences, later Eötvös Loránd Research Network. This work was supported by OTKA grant FK-132133. This work was supported by the ÚNKP-21-3-II-BME-309 and ÚNKP-21-4-I-BME-329. New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. The research reported in this paper and carried out at BME has been supported by the National Laboratory of Artificial Intelligence funded by the NRDIO under the auspices of the Ministry for Innovation and Technology. AB - 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%). LA - English DB - MTMT ER - TY - JOUR AU - Mészáros, Lilla Alexandra AU - Farkas, Attila AU - Madarász, Lajos AU - Bicsár, Rozália AU - Galata, Dorián László AU - Nagy, Brigitta AU - Nagy, Zsombor Kristóf TI - UV/VIS imaging-based PAT tool for drug particle size inspection in intact tablets supported by pattern recognition neural networks JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 620 PY - 2022 SN - 0378-5173 DO - 10.1016/j.ijpharm.2022.121773 UR - https://m2.mtmt.hu/api/publication/32803411 ID - 32803411 N1 - Export Date: 19 May 2022 CODEN: IJPHD Correspondence Address: Nagy, Z.K.; Department of Organic Chemistry and Technology, Műegyetem rakpart 3, Hungary; email: zsknagy@oct.bme.hu LA - English DB - MTMT ER - TY - JOUR AU - Domján, Júlia AU - Pantea, Eszter AU - Gyürkés, Martin AU - Madarász, Lajos AU - Kozák, Dóra AU - Farkas, Attila AU - Horváth, Balázs AU - Benkő, Zsuzsa AU - Nagy, Zsombor Kristóf AU - Marosi, György AU - Hirsch, Edit TI - Real‐time amino acid and glucose monitoring system for the automatic control of nutrient feeding in CHO cell culture using raman spectroscopy JF - BIOTECHNOLOGY JOURNAL J2 - BIOTECHNOL J VL - 17 PY - 2022 IS - 5 PG - 14 SN - 1860-6768 DO - 10.1002/biot.202100395 UR - https://m2.mtmt.hu/api/publication/32633240 ID - 32633240 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Fund of Hungary [FIEK_16-1-2016-0007]; Gedeon Richter's Talentum Foundation; PREMIUM post-doctorate research program of the Hungarian Academy of Sciences; New National Excellence Program of The Ministry for Innovation and Technology [UNKP-20-3-I-BME-306, UNKP-20-3-I-562 BME] Funding text: National Research, Development and Innovation Fund of Hungary, Grant/Award Number: FIEK_16-1-2016-0007; Ph.D. scholarship from Gedeon Richter's Talentum Foundation; PREMIUM post-doctorate research programof the Hungarian Academy of Sciences; UNKP-20-3-I-BME-306, UNKP-20-3-I-562 BME by New National Excellence Program of The Ministry for Innovation and Technology AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Edina AU - Záhonyi, Petra AU - Galata, Dorián László AU - Madarász, Lajos AU - Vass, Panna AU - Farkas, Attila AU - Dhondt, Jens AU - Andersen, Sune K. AU - Vígh, Tamás AU - Verreck, Geert AU - Csontos, István AU - Marosi, György AU - Nagy, Zsombor Kristóf TI - Powder filling of electrospun material in vials: A proof-of-concept study JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 613 PY - 2022 PG - 11 SN - 0378-5173 DO - 10.1016/j.ijpharm.2021.121413 UR - https://m2.mtmt.hu/api/publication/32602243 ID - 32602243 N1 - Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), H-1111 Budapest, Műegyetem rakpart 3, Hungary Oral Solid Dosage, Drug Product Development, Pharmaceutical Development and Manufacturing Sciences, Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, Beerse, B-2340, Belgium Export Date: 25 January 2022 CODEN: IJPHD Correspondence Address: Nagy, Z.K.; Department of Organic Chemistry and Technology, H-1111 Budapest, Műegyetem rakpart 3, Hungary; email: zsknagy@oct.bme.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Domokos, András AU - Madarász, Lajos AU - Stoffán, György Nimród AU - Tacsi, Kornélia AU - Galata, Dorián László AU - Csorba, Kristóf AU - Vass, Panna AU - Nagy, Zsombor Kristóf AU - Pataki, Hajnalka TI - Real-Time Monitoring of Continuous Pharmaceutical Mixed Suspension Mixed Product Removal Crystallization Using Image Analysis JF - ORGANIC PROCESS RESEARCH & DEVELOPMENT J2 - ORG PROCESS RES DEV VL - 26 PY - 2022 IS - 1 SP - 149 EP - 158 PG - 10 SN - 1083-6160 DO - 10.1021/acs.oprd.1c00372 UR - https://m2.mtmt.hu/api/publication/32601462 ID - 32601462 N1 - Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Budapest, H-1111, Hungary Budapest University of Technology and Economics, Department of Automation and Applied Informatics, Budapest, H-1111, Hungary Export Date: 26 January 2022 CODEN: OPRDF Correspondence Address: Vass, P.; Budapest University of Technology and Economics, Hungary; email: panna.vass@oct.bme.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Madarász, Lajos AU - Köte, Á. AU - Hambalkó, Bence AU - Csorba, Kristóf AU - Kovács, V. AU - Lengyel, László AU - Marosi, György AU - Farkas, Attila AU - Nagy, Zsombor Kristóf AU - Domokos, András TI - In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid process understanding and development JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 612 PY - 2022 SN - 0378-5173 DO - 10.1016/j.ijpharm.2021.121280 UR - https://m2.mtmt.hu/api/publication/32546925 ID - 32546925 N1 - Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3, Hungary Department of Automation and Applied Informatics, Budapest University of Technology and Economics, H-1117, Budapest Magyar Tudósok körútja 2 QB-207, Hungary Export Date: 21 December 2021 CODEN: IJPHD Correspondence Address: Nagy, Z.K.; Department of Organic Chemistry and Technology, H-1111 Budapest, Műegyetem rakpart 3, Hungary; email: zsknagy@oct.bme.hu Funding details: Hungarian Scientific Research Fund, OTKA, FK-132133 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: Innovációs és Technológiai Minisztérium Funding text 1: Supported by the ÚNKP-20-3 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. A. Farkas acknowledges the financial support received through the PREMIUM post-doctorate research program of the Hungarian Academy of Sciences, later Eötvös Loránd Research Network. This work was supported by OTKA grant FK-132133. AB - 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 LA - English DB - MTMT ER -