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Advancing tablet lubrication: A systematic comparison of feed frame lubrication and internal lubrication
| Contributor(s):: Jens Bartsch, Markus Thommes, Christopher Mathias, René Brands
For the continuous manufacturing of tablets, internal lubrication is often utilized. Here, lubricant is added to a pre-blend in an additional blending step. However, over-lubrication may occur, with a negative impact on the tablet quality. This study consequently focuses on the...
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Impact of material properties and process parameters on tablet quality in a continuous direct compression line
| Contributor(s):: Pauline H.M. Janssen, Sara Fathollahi Bram Bekaert, Dirk Vanderroost, Timo Roelofs, Valerie Vanhoorne, Chris Vervaet, Bastiaan H.J. Dickhoff
The current paper shows how excipient properties impact the process parameters and the final tablet properties in a fully integrated continuous direct compression line. Blend properties of low-dose (1% w/w) and high-dose (40% w/w) paracetamol formulations were evaluated...
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Twin Screw Granulation: Effects of Properties of Primary Powders
| Contributor(s):: Lute, Sushma, V, Dhenge, Ranjit M., Salman, Agba D.
Lactose and mannitol are some of the most commonly used powders in the pharmaceutical industry. The limited Research Article published so far highlights the effects of process and formulation parameters on the properties of the granules and the tablets produced using these two types of powders...
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Provoking an end-to-end continuous direct compression line with raw materials prone to segregation
| Contributor(s):: Lakio, Satu, Ervasti, Tuomas, Tajarobi, Pirjo, Wikstrom, Hakan, Fransson, Magnus, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Folestad, Staffan, Abrahmsen-Alami, Susanna, Korhonen, Ossi
Continuous manufacturing of solid oral dosage forms is promising for increasing the efficiency and quality of pharmaceutical production and products. In this study a whole train continuous direct compression (CDC) line has been provoked using challenging formulations typically prone to...
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Process Modeling and Simulation of Tableting-An Agent-Based Simulation Methodology for Direct Compression
| Contributor(s):: Martin, NL, Schomberg, AKFinke, JH, Abraham, TGM, Kwade, A, Herrmann, C
In pharmaceutical manufacturing, the utmost aim is reliably producing high quality products. Simulation approaches allow virtual experiments of processes in the planning phase and the implementation of digital twins in operation. The industrial processing of active pharmaceutical ingredients...
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Process analytical technology for continuous manufacturing tableting processing: A case study
| Contributor(s):: Pauli, Victoria, Pellegatti, Laurent, Nguyen Trung, Nhat Quang, Elbaz, Frantz, Ensslin, Simon, Kleinebudde, Peter, Roggo, Yves, Krumme, Markus
The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive technique was employed for the control and monitoring of the tableting step during a continuous manufacturing process. Two NIRS methods were optimized in order to in-line control the blend uniformity in the tablet feed...
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Influence of granulation temperature on particle size distribution of granules in twin-screw granulation (TSG)
| Contributor(s):: Ito, Akihiko, Kleinebudde, Peter
This study investigated an influence of granulation temperature during twin-screw granulation (TSG) on particle size distributions (PSDs). The influence of the granulation temperature on granule size distributions varied, depending on the liquid to solid (L/S) ratio, the kind of binders, the...
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Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets
| Contributor(s):: Fonteyne, Margot, Wickström, Henrika, Peeters, Elisabeth, Vercruysse, Jurgen, Ehlers, Henrik, Peters, Björn-Hendrik, Remon, Jean Paul, Vervaet, Chris, Ketolainen, Jarkko, Sandler, Niklas, Rantanen, Jukka., Naelapää, Kaisa
Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product...
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Impact of blend properties on die filling during tableting
| Contributor(s):: Van Snick, B., Grymonpre, W., Dhondt, J., Pandelaere, K., Di Pretoro, G., Remon, J. P., De Beer, T., Vervaet, C., Vanhoorne, V.
Based on characterization of a wide range of fillers and APIs, thirty divergent blends were composed and subsequently compressed on a rotary tablet press, varying paddle speed and turret speed. The tablet weight variability was determined of 20 grab samples consisting of each 20 tablets....
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Future Supply Chains Enabled by Continuous Processing - Opportunities and Challenges
| Contributor(s):: Jagjit Singh Srai, Markus Krumme, Mauricio Futran, Clive Badman, Craig Johnston
This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily “continuous processing”-based supply chain. The current predominantly “large batch” and centralized manufacturing system designed for the “blockbuster” drug has driven a slow-paced,...
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Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes
| Contributor(s):: Chen, Liang, He, Zizhou, Kunnath, Kuriakose, Zheng, Kai, Kim, Sangah, Dave, Rajesh N.
Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid...
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End-to-end continuous manufacturing of conventional compressed tablets: From flow synthesis to tableting through integrated crystallization and filtration
| Contributor(s):: Domokos, A, Nagy, BGyurkes, M, Farkas, A, Tacsi, K, Pataki, H, Liu, YC, Balogh, A, Firth, P, Szilagyi, B, Marosi, G, Nagy, ZK
An end-to-end continuous pharmaceutical manufacturing process was developed for the production of conventional direct compressed tablets on a proof-of-concept level for the first time. The output reaction mixture of the flow synthesis of acetylsalicylic acid was crystallized continuously in a...
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Effect of force feeder on tablet strength during compression
| Contributor(s):: Narang, Ajit S., Rao, Venkatramana M., Guo, Hang, Lu, Jian, Desai, Divyakant S.
Mechanical strength of tablets is an important quality attribute, which depends on both formulation and process. In this study, the effect of process variables during compression on tablet tensile strength and tabletability (the ratio of tensile strength to compression pressure) was investigated...
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Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders
| Contributor(s):: Grymonpre, W., Verstraete, G., Vanhoorne, V., Remon, J. P., De Beer, T., Vervaet, C.
The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all...
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Continuous manufacturing of tablets with PROMIS-line. Introduction and case studies from continuous feeding, blending and tableting
| Contributor(s):: Simonaho, Simo-Pekka, Ketolainena, Jarkko, Ervasti, Tuomas, Toiviaine, Maunu, Korhonen, Ossi
Drug manufacturing technology is in the midst ofmodernization and continuousmanufacturing of drug products is especially the focus of great interest. The adoption of new manufacturing approaches requires extensive cooperation between industry, regulatory bodies, academics and equipment...
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Assessment and prediction of tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy
| Contributor(s):: Peeters, Elisabeth, Tavares da Silva, Ana Filipa, Toiviainen, Maunu, Van Renterghem, Jeroen, Vercruysse, Jurgen, Juuti, Mikko, Lopes, Joao Almeida, De Beer, Thomas., Vervaet, Chris, Remon, Jean-Paul
This study investigated whether Raman and Near Infrared (NIR) spectroscopy could predict tablet properties. Granules were produced on a continuous line by varying granulation parameters. Tableting process parameters were adjusted to obtain uniform tablet weight and thickness. Spectra were...
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Application of X-Ray Sensors for In-line and Noninvasive Monitoring of Mass Flow Rate in Continuous Tablet Manufacturing
| Contributor(s):: Ganesh, Sudarshan, Troscinski, Rachel, Schmall, Nicholas, Nagy, Zoltan, Reklaitis, Gintaras
The progress in continuous downstream manufacturing of oral solid doses demands effective real-time process management, with monitoring at its core. This study evaluates the feasibility of using a commercial sensor to measure the mass flow rate of the particulates, a critical process variable in...
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Artificial Intelligence Tools for Scaling Up of High Shear Wet Granulation Process
| Contributor(s):: Landin, Mariana
The results presented in this article demonstrate the potential of artificial intelligence tools for predicting the endpoint of the granulation process in high-speed mixer granulators of different scales from 25L to 600L. The combination of neurofuzzy logic and gene expression programing...