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Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line.
Int J Pharm. 2021 Feb 01; 594:120126.IJ

Abstract

Highly homogeneous low-dose (50 μg) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a Continuous Sieving (CS) unit. Throughout the experiments a pre-blend of lactose-monohydrate and corn starch was gravimetrically dosed with 1 kg/h into the TSWG, where they were successfully granulated with the drug containing water-based PVPK30 solution. The wet mass was subsequently dried in the CFBD on a vibratory conveyor belt and finally sieved in the milling unit. Granule production efficiency was maximized by determining the minimal Liquid-to-Solid (L/S) ratio (0.11). Design of Experiments (DoE) were carried out in order to evaluate the influence of the drying process parameters of the CFBD on the Loss-on-Drying (LOD) results. The manufactured granules were compressed into tablets by an industrial tablet rotary press with excellent API homogeneity (RSD < 3%). Significant scale-up was realized with the CM line by increasing the throughput rate to 10 kg/h. The manufactured granules yielded very similar results to the previous small-scale granulation runs. API homogeneity was demonstrated (RSD < 2%) with Blend Uniformity Analysis (BUA). The efficiency of TSWG granulation was compared to High-Shear Granulation (HSG) with the same L/S ratio. The final results have demonstrated that both the liquid distribution and more importantly API homogeneity was better in case of the TSWG granulation (RSD 1.3% vs. 4.5%).

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Authors+Show Affiliations

Fülöp G
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary; Gedeon Richter Plc., Formulation R&D, Gyömrői u. 19-21, H-1103 Budapest, Hungary.
Domokos A
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Galata D
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Szabó E
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Gyürkés M
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Szabó B
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Farkas A
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Madarász L
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Démuth B
Gedeon Richter Plc., Formulation R&D, Gyömrői u. 19-21, H-1103 Budapest, Hungary.
Lendér T
Gedeon Richter Plc., Formulation R&D, Gyömrői u. 19-21, H-1103 Budapest, Hungary.
Nagy T
Gedeon Richter Plc., Formulation R&D, Gyömrői u. 19-21, H-1103 Budapest, Hungary.
Kovács-Kiss D
Gedeon Richter Plc., Formulation R&D, Gyömrői u. 19-21, H-1103 Budapest, Hungary.
Van der Gucht F
ProCepT N.V., Industriepark Rosteyne 4, 9060 Zelzate, Belgium.
Marosi G
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary.
Nagy ZK
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rkp. 3, 1111 Budapest, Hungary. Electronic address: zsknagy@oct.bme.hu.

MeSH

Drug CompoundingExcipientsParticle SizePowdersTabletsTechnology, PharmaceuticalTemperature

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33321167

Citation

Fülöp, G, et al. "Integrated Twin-screw Wet Granulation, Continuous Vibrational Fluid Drying and Milling: a Fully Continuous Powder to Granule Line." International Journal of Pharmaceutics, vol. 594, 2021, p. 120126.
Fülöp G, Domokos A, Galata D, et al. Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line. Int J Pharm. 2021;594:120126.
Fülöp, G., Domokos, A., Galata, D., Szabó, E., Gyürkés, M., Szabó, B., Farkas, A., Madarász, L., Démuth, B., Lendér, T., Nagy, T., Kovács-Kiss, D., Van der Gucht, F., Marosi, G., & Nagy, Z. K. (2021). Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line. International Journal of Pharmaceutics, 594, 120126. https://doi.org/10.1016/j.ijpharm.2020.120126
Fülöp G, et al. Integrated Twin-screw Wet Granulation, Continuous Vibrational Fluid Drying and Milling: a Fully Continuous Powder to Granule Line. Int J Pharm. 2021 Feb 1;594:120126. PubMed PMID: 33321167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line. AU - Fülöp,G, AU - Domokos,A, AU - Galata,D, AU - Szabó,E, AU - Gyürkés,M, AU - Szabó,B, AU - Farkas,A, AU - Madarász,L, AU - Démuth,B, AU - Lendér,T, AU - Nagy,T, AU - Kovács-Kiss,D, AU - Van der Gucht,F, AU - Marosi,G, AU - Nagy,Z K, Y1 - 2020/12/13/ PY - 2020/08/25/received PY - 2020/11/21/revised PY - 2020/11/24/accepted PY - 2020/12/16/pubmed PY - 2021/6/22/medline PY - 2020/12/15/entrez KW - Content uniformity KW - Continuous fluid drying KW - Low-dose KW - Scale-up KW - Twin-screw wet granulation SP - 120126 EP - 120126 JF - International journal of pharmaceutics JO - Int J Pharm VL - 594 N2 - Highly homogeneous low-dose (50 μg) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a Continuous Sieving (CS) unit. Throughout the experiments a pre-blend of lactose-monohydrate and corn starch was gravimetrically dosed with 1 kg/h into the TSWG, where they were successfully granulated with the drug containing water-based PVPK30 solution. The wet mass was subsequently dried in the CFBD on a vibratory conveyor belt and finally sieved in the milling unit. Granule production efficiency was maximized by determining the minimal Liquid-to-Solid (L/S) ratio (0.11). Design of Experiments (DoE) were carried out in order to evaluate the influence of the drying process parameters of the CFBD on the Loss-on-Drying (LOD) results. The manufactured granules were compressed into tablets by an industrial tablet rotary press with excellent API homogeneity (RSD < 3%). Significant scale-up was realized with the CM line by increasing the throughput rate to 10 kg/h. The manufactured granules yielded very similar results to the previous small-scale granulation runs. API homogeneity was demonstrated (RSD < 2%) with Blend Uniformity Analysis (BUA). The efficiency of TSWG granulation was compared to High-Shear Granulation (HSG) with the same L/S ratio. The final results have demonstrated that both the liquid distribution and more importantly API homogeneity was better in case of the TSWG granulation (RSD 1.3% vs. 4.5%). SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/33321167/Integrated_twin_screw_wet_granulation_continuous_vibrational_fluid_drying_and_milling:_A_fully_continuous_powder_to_granule_line_ DB - PRIME DP - Unbound Medicine ER -