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Influence of binder attributes on binder effectiveness in a continuous twin screw wet granulation process via wet and dry binder addition
Contributor(s):: Vandevivere, L., Denduyver, P., Portier, C., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.
The effect of a wide variety of binders on the quality of granules produced via continuous twin screw wet granulation was studied. Anhydrous dicalcium phosphate was used as poorly soluble filler and was granulated applying dry or wet addition of binders. Furthermore, dry and wet binder...
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Influence of filler selection on twin screw foam granulation
Contributor(s):: Rocca, K. E., Weatherley, S., Sheskey, P. J., Thompson, M. R.
The influence of filler selection in wet granulation was studied for the novel case where the binder is delivered as an unstable, semi-rigid aqueous foam to an extrusion process. The work primarily examined the impact of differing concentrations of microcrystalline cellulose (Avicel PH (R) 101)...
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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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Inline Determination of Residence Time distributionin Hot-Melt-Extrusion
Contributor(s):: Wesholowski, Jens, Berghaus, Andreas, Thommes, Markus
In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this...
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Implementing Feedback Granule Size Control in a Continuous DryGranulation Line Using Controlled Impeller Speed of the GranulationUnit, Compaction Force and Gap Width
Contributor(s):: Wilms, Annika, Teske, Andreas, Meier, Robin, Wiedey, Raphael, Kleinebudde, Peter
Purpose: In continuous manufacturing of pharmaceuticals, dry granulation is of interest because of its large throughput capacity and energy efficiency. In order to manufacture solid oral dosage forms continuously, valid control strategies for critical quality attributes should be established. To...
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Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation
Contributor(s):: Vanhoorne, V., Bekaert, B., Peeters, E., De Beer, T., Remon, J-P., Vervaet, C.
In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current...
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Improving Feedability of Highly Adhesive Active Pharmaceutical Ingredients by Silication
Contributor(s):: Escotet-Espinoza, M. Sebastian, Moghtadernejad, Sara, Sanchez, Eric, Cappuyns, Philippe, Van Assche, Ivo, Di Pretoro, Giustino, Ierapetritou, Marianthi, Scicolone, James V., Muzzio, Fernando J.
Purpose: Loss-in-weight feeders play a vital role in assuring blend and content uniformity as well as lot-to-lot powder traceability in continuous manufacturing. Irregular flow from the feeders propagates through the system, potentially resulting in out-of-specification product. Powder properties...
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In line monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using Near Infrared spectroscopy
Contributor(s):: Sierra-Vega, Nobel, Sánchez-Paternina, Adriluz, Maldonado, Nadja, Cárdenas, Vanessa, Romañach, Rodolfo, Mendez, Rafael
Near infrared (NIR) spectroscopy was used to determine the drug concentration in 3% (w/w) acetaminophen blends within the complex flow regime of the tablet press feed frame just before tablet compaction. NIR spectra also provided valuable information on the powder flow behavior within the feed...
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Indirect monitoring of ultralow dose API content in continuous wet granulation and tableting by machine vision
Contributor(s):: Ficzere, Máté, Mészáros, Lilla Alexandra, Madarász, Lajos, Novák, Márk, Nagy, Zsombor Kristóf, Galata, Dorián László
This paper presents new machine vision–based methods for indirect real-time quantification of ultralow drug content during continuous twin-screw wet granulation and tableting. Granulation was performed with a solution containing carvedilol (CAR) as API in the ultralow dose range (0.05 w/w% in the...
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Impact of material properties and process variables on the residence time distribution in twin screw feeding equipment
Contributor(s):: Van Snick, B, Kumar, A, Verstraeten, M, Pandelaere, K, Dhondt, J, Di Pretoro, G, De Beer, T, Vervaet, C, Vanhoorne, V
Screw feeders are integrated as dispensing units in most continuous manufacturing platforms. Hence, characterizing and modelling the residence time distribution (RTD) of materials in feeders is indispensable to understand the traceability of raw materials from the drum till tablet, enabling the...
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Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation
Contributor(s):: Vercruysse, J, Burggraeve, A., Fonteyne, M., Cappuyns, P., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Vervaet, C.
Twin screw granulation (TSG) has been reported by different Research Article groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution...
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Impact of Vertical Blender Unit Parameters on Subsequent Process Parameters and Tablet Properties in a Continuous Direct Compression Line
Contributor(s):: Kreiser, MJ, Wabel, C, Wagner, KG
The continuous manufacturing of solid oral-dosage forms represents an emerging technology among the pharmaceutical industry, where several process steps are combined in one production line. As all mixture components, including the lubricant (magnesium stearate), are passing simultaneously through...
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How to measure coating thickness of tablets: Method comparison of optical coherence tomography, near-infrared spectroscopy and weight-, height- and diameter gain
Contributor(s):: Wahl, P. R., Peter, A., Wolfgang, M., Khinast, J. G.
Film coating of pharmaceutical dosage forms, such as tablets and pellets, can be used to tailor the drug release profile. With that regard, a uniform coating thickness of a single tablet (intra-tablet), all tablets (inter-tablet) and subsequent batches (inter-batch) is crucial. We present a...
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Hypromellose - A traditional pharmaceutical excipient with modern applications in oral and oromucosal drug delivery
Contributor(s):: Maskova, Eliska, Kubova, Katerina, Raimi-Abraham, Bahijja T., Vllasaliu, Driton, Vohlidalova, Eva, Turanek, Jaroslav, Masek, Josef
Hydroxypropylmethylcellulose (HPMC), also known as Hypromellose, is a traditional pharmaceutical excipient widely exploited in oral sustained drug release matrix systems. The choice of numerous viscosity grades and molecular weights available from different manufacturers provides a great...
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Identifying a Loss-in-Weight Feeder Design Space Based on Performance and Material Properties
Contributor(s):: Li, Tianyi, Scicolone, James V. Sanchez, Eric, Muzzio, Fernando J.
Powder properties, such as density and adhesion, can cause large variability in the flow rate of ingredients fed from feeders, which can propagate through the system. Knowing an ideal range of operation and correlating powder properties to process performance can result in faster optimization of...
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Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process
Contributor(s):: Vandevivere, Lise, Vangampelaere, Maxine, Portier, Christoph, de Backere, Cedrine, Hausler, Olaf, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable...
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Identifying overarching excipient properties towards an in-depth understanding of process and product performance for continuous twin-screw wet granulation
Contributor(s):: Willecke, N., Szepes, A., Wunderlich, M., Remon, J. P., Vervaet, C., De Beer, T.
The overall objective of this work is to understand how excipient characteristics influence the process and product performance for a continuous twin-screw wet granulation process. The knowledge gained through this study is intended to be used for a Quality by Design (QbD)-based formulation...
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Impact of blend properties and process variables on the blending performance
Contributor(s):: Bekaert, B, Grymonpre, W, Novikova, A, Vervaet, C, Vanhoorne, V
In this study, quantitative relationships were established between blend properties, process settings and blending responses via multivariate data-analysis. Four divergent binary blends were composed in three different ratios and processed at various throughputs and impeller speeds. Additionally,...
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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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Granulation of increasingly hydrophobic formulations using a twin screw granulator
Contributor(s):: Yu, Shen, Reynolds, Gavin K., Huang, Zhenyu, de Matas, Marcel, Salman, Agba D.
The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has...
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Grey-Box Approach for the Prediction of Variable Residence Time Distribution in Continuous Pharmaceutical Manufacturing
Contributor(s):: Elkhashap, A, Meier, R, Stenger, D, Abel, D
Axial dispersion models are used for the prediction of residence time distribution (RTD) of the flow occurring in various processes. Such models are essential for the understanding of the flow dynamics allowing monitoring, control and material tracing specially in the scope of continuous...
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Heat Transfer Evaluation During Twin-Screw Wet Granulation in View of Detailed Process Understanding
Contributor(s):: Stauffer, Fanny, Ryckaert, Alexander, Van Hauwermeiren, Daan, Funke, Adrian, Djuric, Dejan, Nopens, Ingmar, De Beer, Thomas
During the last decade, the pharmaceutical industry has shown a growing interest in continuous twin-screw granulation (TSG). Despite flourishing literature on TSG, limited studies focused on fundamental process understanding on its mechanisms. In current study, granule quality attributes along...
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Hot melt extrusion technology for continuous manufacturing
Contributor(s):: Furqan Tahir, Lovett. David
Hot melt extrusion (HME), a manufacturing technique traditionally used in the plastic and food industries, is now attracting significant interest from the pharmaceutical manufacturing sector. This is primarily because HME enables the continuous manufacture of a wide variety of dosage...
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Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation
Contributor(s):: Patil, H, Tiwari, RV, Repka, MA
Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently...