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Parametric Study of Residence Time Distributions and Granulation Kinetics as a Basis for Process Modeling of Twin-Screw Wet Granulation
09 Jun 2023 | Contributor(s):: Plath, Timo, Korte, Carolin, Sivanesapillai, Rakulan, Weinhart, Thomas
Twin-screw wet granulation is a crucial unit operation in shifting from pharmaceutical batch to continuous processes, but granulation kinetics as well as residence times are yet poorly understood. Experimental findings are highly dependent on screw configuration as well as formulation, and thus...
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On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Development of a Highly Efficient Synthesis for Ciprofloxacin
09 Jun 2023 | Contributor(s):: Armstrong, Cameron, Miyai, Yuma, Formosa, Anna, Thomas Dale, Chen, Esther, Hart, Travis, Schultz, Victor, Desai, Bimbisar, Cai, Angela, Almasy, Alexandra, Jensen, Klavs, Roper, Thomas
The experimental approach taken and challenges overcome in developing a high-purity production (>100 g) scale process for the telescoped synthesis of the antibiotic ciprofloxacin is outlined. The process was first optimized for each step sequentially with regard to purity and yield, with...
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Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets
09 Jun 2023 | Contributor(s):: Taipale-Kovalainen, Krista, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Korhonen, Ossi
The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental...
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Effects of Process and Design Parameters on Granule Size Distribution in a Continuous High Shear Granulation Process
09 Jun 2023 | Contributor(s):: Meng, Wei, Oka, Sarang, Liu, Xue, Omer, Thamer, Ramachandran, Rohit, Muzzio, Fernando J.
Wet granulation is widely used in the pharmaceutical industry. This advantageous technology is capable of enhancing compression and powder handling, decreasing ingredient segregation, and promoting blend and content uniformity. Currently, a high level of interest exists in the continuous version...
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Determining key parameters of continuous wet granulation for tablet quality and productivity: A case in ethenzamide
09 Jun 2023 | Contributor(s):: Matsunami, K, Nagato, THasegawa, K, Sugiyama, H
This paper aims to determine key parameters that affect tablet quality and productivity in continuous tablet manufacturing. Experiments were performed based on design of experiments using a continuous high-shear granulator and ethenzamide as the active pharmaceutical ingredient. To guide a...
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Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API
09 Jun 2023 | Contributor(s):: Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous Research Article identified lactose/MCC/HPMC as a...
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Continuous twin screw granulation: Influence of process and formulation variables on granule quality attributes of model formulations
09 Jun 2023 | Contributor(s):: Portier, Christoph, Pandelaere, Kenny, Delaet, Urbain, Vigh, Tamas, Kumar, Ashish, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
In recent years, continuous manufacturing techniques, such as twin screw wet granulation, have gained significant momentum. Due to the large diversity of the (model) formulations and equipment, it is often difficult to generalize conclusions about the importance of process settings. As only...
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Continuous twin screw granulation: Robustness of lactose/MCC-based formulations
09 Jun 2023 | Contributor(s):: Portier, Christoph, De Vriendt, Charlotte, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response...
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Continuous Single-Step Wet Granulation with Integrated in-Barrel-Drying
09 Jun 2023 | 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 granulation: A complex interplay between formulation properties, process settings and screw design
09 Jun 2023 | 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 manufacturing of a pharmaceutical cream: Investigating continuous powder dispersing and residence time distribution (RTD)
09 Jun 2023 | Contributor(s):: Bostijn, N, Van, Renterghem, JVanbillemont, B, Dhondt, W, Vervaet, C, De;Beer, T
Recently, an innovative continuous manufacturing technology for a pharmaceutical oral suspension was proposed, based on two consecutive mixing units. A limitation of this technology is the need to dissolve or disperse powder-based raw materials in a liquid via a batch step before continuous...
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Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation
09 Jun 2023 | Contributor(s):: Matsunami, Kensaku, Ryckaert, Alexander, Peeters, Michiel, Badr, Sara, Sugiyama, Hirokazu, Nopens, Ingmar, De Beer, Thomas
Toward further implementation of continuous tablet manufacturing, one key issue is the time needed for start-up operation because it could lead to lower product yield and reduced economic performance. The behavior of the start-up operation is not well understood; moreover, the definition of the...
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Analytical Method Quality by Design for an On-Line Near-Infrared Method to Monitor Blend Potency and Uniformity
09 Jun 2023 | Contributor(s):: Corredor, Claudia, Bu, Xin, McCann, Ryan, Dougherty, Jeffrey, Stevens, Tim, Both, Douglas, Shah, Pankaj
In this work, an example of analytical method quality by design (AQbD) principles applied to an in-line NIR method to monitor blend potency and uniformity in the manufacturing of an oral solid dosage product is presented. An integrated process analytical technology (PAT) method was developed...
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A comprehensive analysis and optimization of continuous twin-screw granulation processes via sequential experimentation strategy
09 Jun 2023 | Contributor(s):: Meng, Wei, Rao, Kallakuri Suparna, Snee, Ronald D., Ramachandran, Rohit., Muzzio, Fernando J
Nowadays twin-screw granulation has been emerging as an attractive continuous wet granulation technique. This study was geared towards better process design and understanding with emphasis on bridging the knowledge gap between input and output variables by employing sequential experimentation...