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Continuous Single-Step Wet Granulation with Integrated in-Barrel-Drying
Contributor(s):: Schmidt, Adrian, de Waard, Hans, Kleinebudde, Peter, Krumme, Markus
Purpose It was investigated if continuous wet granulation and drying could be combined in a twin-screw granulator with the aimto provide (pre-) dried granules in a single-step process, i.e. in-barrel-drying. Methods To have a consistent and robust material propulsionmechanism, a twin-screw...
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Continuous twin screw extrusion for the wet granulation of lactose
Contributor(s):: Keleb, EI, Vermeire, A, Vervaet, C, Remon, JP
The Suitability of continuous twin screw extrusion for the wet granulation of a-lactose monohydrate was studied and compared with conventional high shear granulation. The influence of process parameters (screw speed and total input rate) and formulation variables (water and polyvinylpyrrolidone...
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Continuous twin screw granulation - An advanced alternative granulation technology for use in the pharmaceutical industry
Contributor(s):: Bandari, Suresh, Nyavanandi, Dinesh, Kallakunta, Venkata Raman, Janga, Kartik Yadav, Sarabu, Sandeep, Butreddy, Arun, Repka, Michael A.
Hot melt extrusion has been an exciting technology in the pharmaceutical field owing to its novel applicability. Twin-screw granulation presents a great potential and offers many advantages relative to conventional granulation processes. Different twin-screw granulation techniques, such as...
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Continuous twin screw granulation and fluid bed drying: A mechanistic scaling approach focusing optimal tablet properties
Contributor(s):: Menth, Judith, Maus, Martin, Wagner, Karl G.
This study provides the results of investigation on scaling approaches for three differently-sized continuous granulation lines, each consisting of a twin screw wet granulation process and a continuous fluid bed drying process. To check the initial scaling approach with regard to granule and...
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Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design
Contributor(s):: Portier, Christoph, Pandelaere, KDelaet, U, Vigh, T, Di, Pretoro, G, De, Beer, T, Vervaet, C, Vanhoorne, V
Due to the numerous advantages over batch manufacturing, continuous manufacturing techniques such as twin screw wet granulation are rapidly gaining importance in pharmaceutical production. Since a large knowledge gap on the importance of formulation variables exists, this study systematically...
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Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design
Contributor(s):: Portier, Christoph, Vervaet, Chris, Vanhoorne, Valérie
Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in...
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Continuous Melt Granulation for Taste-Masking of Ibuprofen
Contributor(s):: Forster, Seth P., Lebo, David B.
This book covers key aspects of the continuous manufacturing of pharmaceuticals. The first part provides an overview of key chemical engineering principles and the current regulatory environment. The second covers existing technologies for manufacturing both small-molecule-based products and...
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Continuous Pharmaceutical Processing
Contributor(s):: Zoltan K Nagy, Arwa El Hagrasy, Jim Litster
Covers chemical engineering principles, regulatory aspects, primary and secondary manufacturing, process analytical technology and quality-by-design
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Continuous processing and the applications of online tools in pharmaceutical product manufacture: developments and examples
Contributor(s):: Ooi, Shing Minga, Sarkar, Srimantaa, Van Varenbergh, Grietb, Schoeters, Krisb, Heng, Paul Wan Sia
Continuous processing and production in pharmaceutical manufacturing has received increased attention in recent years mainly due to the industries’ pressing needs for more efficient, cost-effective processes and production, as well as regulatory facilitation. To achieve optimum product quality,...
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Continuous manufacturing of delta mannitol by cospray drying with PVP
Contributor(s):: Vanhoorne, V., Van Bockstal, P-J., Van Snick, B., Peeters, E., Monteyne, T., Gomes, P., De Beer, T., Remon, J. P., Vervaet, C.
Mannitol is a frequently used diluent in the production of tablets due to its non-hygroscopic character and low drug interaction potential. Although the delta-polymorph of mannitol has superior tabletability in comparison to alpha- and beta-mannitol, the latter are most commonly used because...
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Continuous Manufacturing of Ketoprofen Delayed Release Pellets Using Melt Extrusion Technology: Application of QbD Design Space, Inline Near Infrared, and Inline Pellet Size Analysis
Contributor(s):: Vo, Anh, Kutz, Gerd, He, Herman, Narala, Sagar, Bandari, Suresh, Repka, Michael A.
Delayed-release dosage forms are mainly manufactured as batch processes and include coated tablets, pellets, or particles with gastric resistant polymers. Authors propose a novel approach using the hot-melt extrusion technique to prepare delayed release dosage forms via a continuous manufacturing...
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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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Continuous manufacturing of pharmaceuticals
Contributor(s):: Johannes Khinast, Jukka Rantanen
A comprehensive look at existing technologies and processes for continuous manufacturing of pharmaceuticals.As rising costs outpace new drug development, the pharmaceutical industry has come under intense pressure to improve the efficiency of its manufacturing processes. Continuous process...
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Continuous granulation in the pharmaceutical industry
Contributor(s):: Vervaet, C, Remon, JP
Traditionally the manufacturing of pharmaceutical dosage forms has been a batch-wise process and continuous processes have limited applications in a pharmaceutical manufacturing plant. However, several factors (reduction of cost, improved process efficiency, optimal use of equipment, flexibility...
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Continuous direct compression as manufacturing platform for sustained release tablets
Contributor(s):: Vanhoorne, V, Holman, J., Cunningham, C., Kumar, A., Vercruysse, J., De Beer, T., Remon, J. P, Vervaet, C
This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard...
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Continuous direct compression: Development of an empirical predictive model and challenges regarding PAT implementation
Contributor(s):: Bekaert, B., Van Snick, B., Pandelaere, K., Dhondt, J., Di Pretoro, G., De Beer, T., Vervaet, C., Vanhoorne, V.
In this study, an empirical predictive model was developed based on the quantitative relationships between blend properties, critical quality attributes (CQA) and critical process parameters (CPP) related to blending and tableting. The blend uniformity and API concentration in the tablets were...
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Continuous direct tablet compression: effects of impeller rotation rate, total feed rate and drug content on the tablet properties and drug release
Contributor(s):: Jarvinen, Maiju A., Paaso, Janne, Paavola, Marko, Leiviska, Kauko, Juuti, Mikko, Muzzio, Fernando, Jarvinen, Kristiina
Context: Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages. Objective: This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process....
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Comparison of a continuous ring layer wet granulation process with batch high shear and fluidized bed granulation processes
Contributor(s):: Jarvinen, MA, Paavola, M, Poutiainen, S, Itkonen, P, Pasanen, V, Uljas, K, Leiviska, K, Juuti, M, Ketolainen, J, Jarvinen, K
The traditional batch wet granulation processes encounter several challenges, such as problems in the scale-up step, batch-to-batch variability together with the multivariate and difficult to control nature of the process. A continuous wet granulation technique could be a possible solution for...
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Concentration monitoring with near infrared chemical imaging in a tableting press
Contributor(s):: Dalvi, Himmat, Fauteux-Lefebvre, Clémence, Guay, Jean-Maxime, Abatzoglou, Nicolas, Gosselin, Ryan
Monitoring powder potency and homogeneity is important in achieving real-time release testing in a continuous tablet manufacturing operation. If quality related issues are encountered, monitoring powder potency inside a feed frame offers a last opportunity to intervene in the process before...
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Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation
Contributor(s):: Kumar, Ashish, Vercruysse, Jurgen, Vanhoorne, Valerie, Toiviainen, Maunu, Panouillot, Pierre-Emmanuel, Juuti, Mikko, Vervaet, Chris, Remon, Jean Paul, Gernaey, Krist V., De Beer, Thomas, Nopens, Ingmar
Twin-screw granulation is a promising continuous alternative for traditional batchwise wet granulation processes. The twin-screw granulator (TSG) screws consist of transport and kneading element modules. Therefore, the granulation to a large extent is governed by the residence time distribution...
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Continuous blending monitored and feedback controlled by machine vision-based PAT tool
Contributor(s):: Lászlo Galata, Dorián, Mészaros, Lilla, Ficzere Máté, Vass, Panna, Nagy, Brigitta, Szabó, Edina, Domokos, András, Farkas, Attila, Csontos, István, Marosi, György, Nagy, Zsombor Kristóf
In a continuous powder blending process machine vision is utilized as a Process Analytical Technology (PAT) tool. While near-infrared (NIR) and Raman spectroscopy are reliable methods in this field, measurements become challenging when concentrations below 2 w/w% are quantified. However, an...
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Characterizing drug product continuous manufacturing residence time distributions of major/minor excipient step changes using near infrared spectroscopy and process parameters
Contributor(s):: Shi, Zhenqi, Manley, Leo
The material residence time distribution in a continuous manufacturing process can be utilized to develop, design and justify the process control strategy. This paper successfully demonstrates using both major and minor formulation component step changes to determine the system response using...
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Compaction properties of melt coated coarse drug particles
Contributor(s):: Gren, T, Nystrom, C
Xylitol and stearic acid were applied onto the surfaces of coarse particles of paracetamol and acetylsalicylic acid by continuous multipurpose melt technology. The effect of melt coating on radial and axial tensile strength was studied and compared to that of dry mixing of paracetamol and...
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Challenges in tracing material flow passing a loss-in-weight feeder in continuous manufacturing processes
Contributor(s):: Peterwitz, Moritz, Gerling, Sina, Schembecker, Gerhard
Loss-in-weight feeders are an integral part of most continuous manufacturing processes, ensuring a constant mass flow. The feeders cause a significant degree of back-mixing in such lines. Understanding back-mixing is essential for the treatment of disturbances. However, feeders refilled...
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Challenges, opportunities and recent advances in near infrared spectroscopy applications for monitoring blend uniformity in the continuous manufacturing of solid oral dosage forms
Contributor(s):: Velez, Natasha L., Drennen, James K., Anderson, Carl A.
Near infrared (NIR) spectroscopy has been widely recognized as a powerful PAT tool for monitoring blend uniformity in continuous manufacturing (CM) processes. However, the dynamic nature of the powder stream and the fast rate at which it moves, compared to batch processes, introduces challenges...