The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Ravendra Singh - One of the best experts on this subject based on the ideXlab platform.
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a validated model for design and evaluation of control architectures for a continuous Tablet compaction process
Processes, 2017Co-Authors: Fernando N. Barros, Aparajith Bhaskar, Ravendra SinghAbstract:The systematic design of an advanced and efficient control strategy for controlling critical quality attributes of the Tablet compaction operation is necessary to increase the robustness of a continuous pharmaceutical manufacturing process and for real time release. A process model plays a very important role to design, evaluate and tune the control system. However, much less attention has been made to develop a validated control relevant model for Tablet compaction process that can be systematically applied for design, evaluation, tuning and thereby implementation of the control system. In this work, a dynamic Tablet compaction model capable of predicting linear and nonlinear process responses has been successfully developed and validated. The nonlinear model is based on a series of transfer functions and static polynomial models. The model has been applied for control system design, tuning and evaluation and thereby facilitate the control system implementation into the pilot-plant with less time and resources. The best performing control algorithm was used in the implementation and evaluation of different strategies for control of Tablet Weight and breaking force. A characterization of the evaluated control strategies has been presented and can serve as a guideline for the selection of the adequate control strategy for a given Tablet compaction setup. A strategy based on a multiple input multiple output (MIMO) model predictive controller (MPC), developed using the simulation environment, has been implemented in a Tablet press unit, verifying the relevance of the simulation tool.
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Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press
Journal of Pharmaceutical Innovation, 2017Co-Authors: Nicholas Townsend Haas, Marianthi G. Ierapetritou, Ravendra SinghAbstract:In continuous pharmaceutical manufacturing, real-time precise control of critical quality attributes (CQAs) is necessary for quality by design (QbD)-based manufacturing and real-time release (RTR) with minimum consumption of time, space, and resources. Pharmaceutical Tablets can be produced through different routes with a common Tablet press unit operation always placed at the end of the manufacturing process. Therefore, the Tablet press is a crucial unit operation directly influencing the CQAs irrespective of manufacturing routes. Despite this, little attention has been paid to the development of an advanced efficient control system for the Tablet press. Process modeling can be used as an efficient virtual experimentation tool to design, compare, and evaluate different control systems. We developed a model in Simulink (Mathworks) that includes two master control loops for Tablet Weight and hardness and a slave feedback loop controlling the compaction force applied to each Tablet. We examined the performance of different control strategies based on proportional integral derivative (PID) control and model predictive control (MPC), as well as feedforward/feedback control. We found that a hybrid MPC-PID control strategy outperforms the PID-only control strategy. We also observed that the addition of a feedforward controller further improves the performance of the hybrid MPC-PID control strategy.
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Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press
Journal of Pharmaceutical Innovation, 2017Co-Authors: Nicholas Townsend Haas, Marianthi G. Ierapetritou, Ravendra SinghAbstract:© 2017, Springer Science+Business Media New York.In continuous pharmaceutical manufacturing, real-time precise control of critical quality attributes (CQAs) is necessary for quality by design (QbD)-based manufacturing and real-time release (RTR) with minimum consumption of time, space, and resources. Pharmaceutical Tablets can be produced through different routes with a common Tablet press unit operation always placed at the end of the manufacturing process. Therefore, the Tablet press is a crucial unit operation directly influencing the CQAs irrespective of manufacturing routes. Despite this, little attention has been paid to the development of an advanced efficient control system for the Tablet press. Process modeling can be used as an efficient virtual experimentation tool to design, compare, and evaluate different control systems. We developed a model in Simulink (Mathworks) that includes two master control loops for Tablet Weight and hardness and a slave feedback loop controlling the compaction force applied to each Tablet. We examined the performance of different control strategies based on proportional integral derivative (PID) control and model predictive control (MPC), as well as feedforward/feedback control. We found that a hybrid MPC-PID control strategy outperforms the PID-only control strategy. We also observed that the addition of a feedforward controller further improves the performance of the hybrid MPC-PID control strategy.
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Development and implementation of an advanced model predictive control system into continuous pharmaceutical Tablet compaction process
International Journal of Pharmaceutics, 2017Co-Authors: Aparajith Bhaskar, Fernando N. Barros, Ravendra SinghAbstract:In the context of continuous pharmaceutical oral dosage manufacturing, a control system is essential to ensure that the critical quality attributes (CQAs) are maintained within the regulatory constraints by mitigating variations generated in upstream operations. Such a system is essential to the Quality by Design (QbD) paradigm shift, which can ensure that predefined end quality attributes are achieved within an optimal economic and time bracket. In this work, an advanced model predictive control (MPC) architecture integrated with a novel real-time Tablet Weight measurement method has been development and implemented into a continuous direct compaction Tablet manufacturing pilot-plant. The proposed control architecture has the potential to control Tablet Weight and Tablet breaking force simultaneously by systematically decoupling and cascading the control loops. The model predictive control algorithm was experimentally found to be superior to the PID (proportional, integral and derivative) controller and thus, can be utilized for a wide range of applications to improve the quality of pharmaceutical products in continuous manufacturing. The MPC was used to control main compression force and pre compression force using main compression height and fill depth respectively as the actuators. The introduction of this methodology leads to new ways of developing MPC models, Tablet Weight measurement methods and control strategies that enhance the manufacturability and quality of pharmaceutical Tablets.
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real time monitoring of powder blend bulk density for coupled feed forward feed back control of a continuous direct compaction Tablet manufacturing process
International Journal of Pharmaceutics, 2015Co-Authors: Ravendra Singh, Marianthi G. Ierapetritou, Rodolfo J. Romañach, Andres D Romanospino, Rohit RamachandranAbstract:Abstract The pharmaceutical industry is strictly regulated, where precise and accurate control of the end product quality is necessary to ensure the effectiveness of the drug products. For such control, the process and raw materials variability ideally need to be fed-forward in real time into an automatic control system so that a proactive action can be taken before it can affect the end product quality. Variations in raw material properties (e.g., particle size), feeder hopper level, amount of lubrication, milling and blending action, applied shear in different processing stages can affect the blend density significantly and thereby Tablet Weight, hardness and dissolution. Therefore, real time monitoring of powder bulk density variability and its incorporation into the automatic control system so that its effect can be mitigated proactively and efficiently is highly desired. However, real time monitoring of powder bulk density is still a challenging task because of different level of complexities. In this work, powder bulk density which has a significant effect on the critical quality attributes (CQA’s) has been monitored in real time in a pilot-plant facility, using a NIR sensor. The sensitivity of the powder bulk density on critical process parameters (CPP’s) and CQA’s has been analyzed and thereby feed-forward controller has been designed. The measured signal can be used for feed-forward control so that the corrective actions on the density variations can be taken before they can influence the product quality. The coupled feed-forward/feed-back control system demonstrates improved control performance and improvements in the final product quality in the presence of process and raw material variations.
Fernando J. Muzzio - One of the best experts on this subject based on the ideXlab platform.
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prediction of Tablet Weight variability in continuous manufacturing
International Journal of Pharmaceutics, 2020Co-Authors: Sonia M Razavi, Philippe Cappuyns, James V Scicolone, Ronald D Snee, Ashish Kumar, Johny Bertels, Ivo Van Assche, Alberto M Cuitino, Fernando J. MuzzioAbstract:This paper provides a method for prediction of Weight variability of Tablets made in rotary Tablet presses as a function of material attributes and processing parameters. The goal was to be able to predict whether or not a formulation is suitable for direct compaction continuous manufacturing using the Tablet Weight variability as a criterion. The work focused on identifying the significant factors affecting the Weight variability in Tablets, within the design space studied. A wide range of blends with different powder properties were prepared. It was shown that among powder properties, cohesion, bulk density, and particle size were the most significant and sufficient material attributes to explain Tablet Weight variability. A response surface model was built and validated with three different blends. The model is not formulation dependent and can be expanded to include other blend properties or processing parameters effects.
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Mixing order of glidant and lubricant – Influence on powder and Tablet properties
International Journal of Pharmaceutics, 2011Co-Authors: Kalyana Pingali, Alberto M Cuitino, Rafael Mendez, Bozena Michniak-kohn, Daniel R. Lewis, Fernando J. MuzzioAbstract:The main objective of the present work was to study the effect of mixing order of Cab-O-Sil (CS) and magnesium stearate (MgSt) and microlayers during mixing on blend and Tablet properties. A first set of pharmaceutical blend containing Avicel PH200, Pharmatose and micronized acetaminophen was prepared with three mixing orders (mixing order-1: CS added first; mixing order-2: MgSt added first; mixing order-3: CS and MgSt added together). All the blends were subjected to a shear rate of 80 rpm and strain of 40, 160 and 640 revolutions in a controlled shear environment resulting in nine different blends. A second set of nine blends was prepared by replacing Avicel PH200 with Avicel PH102. A total of eighteen blends thus prepared were tested for powder hydrophobicity, powder flow, Tablet Weight, Tablet hardness and Tablet dissolution. Results indicated that powder hydrophobicity increased significantly for mixing order-1. Intermediate hydrophobic behavior was found for mixing order-3. Additionally, mixing order 1 resulted in improved powder flow properties, low Weight variability, higher average Tablet Weight and slow drug release rates. Dissolution profiles obtained were found to be strongly dependent not only on the mixing order of flowing agents, but also on the strain and the resulting hydrophobicity.
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a modeling approach for understanding effects of powder flow properties on Tablet Weight variability
Powder Technology, 2009Co-Authors: Amit Mehrotra, M. S. Tomassone, B. Chaudhuri, Akhmad Faqih, Fernando J. MuzzioAbstract:Abstract In this paper we focus on the effect of cohesion and compression speed on the outcome of the compression process for both monodisperse and polydisperse granular systems. A three dimensional discrete element model (DEM) which incorporates static and dynamic friction is used in this study to simulate die filling, and the compaction and decompaction of cohesive granular system in a confined cylindrical die similar to those used in a commercial Tablet press driving the pre-compressive stage. The magnitude of the cohesive force is represented in terms of a parameter K = Fcohes/mg, where K is called the bond number and is the measure of cohesiveness. Force displacement curves are used to characterize the compression and deformation properties of the materials and are obtained by measuring the force on the upper punch and the corresponding displacements in the die. Results show that a considerable more energy is needed to compress the cohesive material as compared to free flowing materials. It is found that the time required to fill the die strongly depends on the cohesion of the material. The energy for the Tableting process is directly proportional to the upper punch speed.
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A modeling approach for understanding effects of powder flow properties on Tablet Weight variability
Powder Technology, 2009Co-Authors: Akhil Mehrotra, M. S. Tomassone, B. Chaudhuri, Akhmad Faqih, Fernando J. MuzzioAbstract:In this paper we focus on the effect of cohesion and compression speed on the outcome of the compression process for both monodisperse and polydisperse granular systems. A three dimensional discrete element model (DEM) which incorporates static and dynamic friction is used in this study to simulate die filling, and the compaction and decompaction of cohesive granular system in a confined cylindrical die similar to those used in a commercial Tablet press driving the pre-compressive stage. The magnitude of the cohesive force is represented in terms of a parameter K = Fcohes/mg, where K is called the bond number and is the measure of cohesiveness. Force displacement curves are used to characterize the compression and deformation properties of the materials and are obtained by measuring the force on the upper punch and the corresponding displacements in the die. Results show that a considerable more energy is needed to compress the cohesive material as compared to free flowing materials. It is found that the time required to fill the die strongly depends on the cohesion of the material. The energy for the Tableting process is directly proportional to the upper punch speed. © 2008 Elsevier B.V. All rights reserved.
Jean Paul Remon - One of the best experts on this subject based on the ideXlab platform.
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Impact of blend properties on die filling during Tableting.
International Journal of Pharmaceutics, 2018Co-Authors: B. Van Snick, Chris Vervaet, Jean Paul Remon, W. Grymonpré, Jens Dhondt, Kenny Pandelaere, G. Di Pretoro, T. De Beer, Valérie VanhoorneAbstract:Abstract 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. Additionally, the bulk residence time, ejection force, pre-compression displacement, main compression force, die fill fraction and feed frame fill fraction were determined during each run. Multivariate data analysis was applied to investigate the relation between the process parameters, blend characteristics, product and process responses. Blends with metoprolol tartrate as API showed high ejection forces. This behavior could be linked to the high wall friction value of metoprolol tartrate. The main responses related to the die filling could be predicted via a PLS model based on blend characteristics. Tablet Weight variability was highly correlated with the variability on pre-compression displacement and main compression force. A good predictive model for Tablet Weight variability was obtained taking the porosity, wall friction angle, flowability, density, compressibility and permeability into account. Additionally, turret speed and paddle speed were included in the calibration of the model. The applied approach can save resources (material, time) during early drug product development.
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Assessment and prediction of Tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy
Asian Journal of Pharmaceutical Sciences, 2016Co-Authors: Elisabeth Peeters, Jurgen Vercruysse, Thomas De Beer, Chris Vervaet, Ana Tavares Da Silva, Maunu Toiviainen, Jeroen Van Renterghem, Mikko Juuti, João A. Lopes, Jean Paul RemonAbstract: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 collected offline and Tablet properties determined with traditional analyzing methods. Partial Least Squares (PLS) regression was used to correlate spectral information to Tablet properties, but predictive models couldn't be established. Principal component analysis (PCA) was effectively used to distinguish theophylline concentrations and hydration levels and multiple linear regression (MLR) analysis allowed insight on how granulation parameters affect granule and Tablet properties.
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reduction of Tablet Weight variability by optimizing paddle speed in the forced feeder of a high speed rotary Tablet press
Drug Development and Industrial Pharmacy, 2015Co-Authors: Elisabeth Peeters, Thomas De Beer, Chris Vervaet, Jean Paul RemonAbstract:AbstractContext: Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release.Objective: The aim of this study was to investigate the influence of paddle speeds and fill depth at different Tableting speeds on the Weight and Weight variability of Tablets.Materials and methods: Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary Tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured.Results and discussion: Analysis of the DoE revealed that paddle speeds are of minor importance for Tablet Weight but significantly affect volume of powder inside the feeder in...
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Use of a continuous twin screw granulation and drying system during formulation development and process optimization
European Journal of Pharmaceutics and Biopharmaceutics, 2015Co-Authors: Jurgen Vercruysse, U. Delaet, I. Van Assche, Philippe Cappuyns, Margot Fonteyne, Thomas De Beer, E Peeters, Jean Paul Remon, Chris VervaetAbstract:Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and Tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P Tablet press (Tablet Weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1 h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as Tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1 h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating granule and Tablet quality attributes were obtained during the start-up phase of the 1 h run. For the single cell runs, granule and Tablet properties were comparable with results obtained during the second part of the 1 h run (after start-up). Although deviating granule quality (particle size distribution and Hausner ratio) was observed due to the divergent design of the ConsiGma™-1 unit and the ConsiGma™-25 system (horizontal set-up) used in this study, Tablet quality produced from granules processed with the ConsiGma™-1 system was predictive for Tablet quality obtained during continuous production using the ConsiGma™-25 system.
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Stability and repeatability of a continuous twin screw granulation and drying system
European Journal of Pharmaceutics and Biopharmaceutics, 2013Co-Authors: Jurgen Vercruysse, U. Delaet, Philippe Cappuyns, Jean Paul Remon, T. De Beer, I. Van Assche, F. Arata, G. Caporicci, Chris VervaetAbstract:Abstract The aim of this study was to investigate the process transfer of a commercially available product from the current batch fluid bed granulation and drying production method to an innovative continuously operating “from powder to Tablet” production line using twin screw granulation as an intermediate granulation step. By monitoring process outcomes (torque, water temperature at the granulator jacket inlet, differential pressure over the dryer filters, and temperature mill screen) and granule and Tablet quality in function of process time, the stability and repeatability during long production runs were determined. Three consecutive 5 h “from powder to Tablet” production runs were performed using the ConsiGma™-25 system (GEA Pharma Systems, Collette™, Wommelgem, Belgium). A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch, and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm and 800 rpm), granules were in-line blended with magnesium stearate and directly compressed using a Modul™ P Tablet press (Tablet Weight: 430 mg, main compression force: 12 kN). Granule (loss on drying, particle size distribution, friability, flow) and Tablet (Weight uniformity, hardness, thickness, friability, content uniformity, disintegration time, and dissolution) quality was evaluated in function of process time. For each of the logged process outcomes, a stabilization period was needed to reach steady-state conditions. Slightly deviating particle size distribution and friability results for milled granules were observed during start-up due to initial layering of the mill screen. However, no deviating Tablet quality was detected in function of process time. For multiple hours, granule and Tablet quality was constant in function of process time. Furthermore, process data trends were highly repeatable. Consequently, the ConsiGma™-25 system can be considered as a stable and repeatable system for the continuous production of Tablets via wet granulation.
Chris Vervaet - One of the best experts on this subject based on the ideXlab platform.
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Impact of blend properties on die filling during Tableting.
International Journal of Pharmaceutics, 2018Co-Authors: B. Van Snick, Chris Vervaet, Jean Paul Remon, W. Grymonpré, Jens Dhondt, Kenny Pandelaere, G. Di Pretoro, T. De Beer, Valérie VanhoorneAbstract:Abstract 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. Additionally, the bulk residence time, ejection force, pre-compression displacement, main compression force, die fill fraction and feed frame fill fraction were determined during each run. Multivariate data analysis was applied to investigate the relation between the process parameters, blend characteristics, product and process responses. Blends with metoprolol tartrate as API showed high ejection forces. This behavior could be linked to the high wall friction value of metoprolol tartrate. The main responses related to the die filling could be predicted via a PLS model based on blend characteristics. Tablet Weight variability was highly correlated with the variability on pre-compression displacement and main compression force. A good predictive model for Tablet Weight variability was obtained taking the porosity, wall friction angle, flowability, density, compressibility and permeability into account. Additionally, turret speed and paddle speed were included in the calibration of the model. The applied approach can save resources (material, time) during early drug product development.
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Assessment and prediction of Tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy
Asian Journal of Pharmaceutical Sciences, 2016Co-Authors: Elisabeth Peeters, Jurgen Vercruysse, Thomas De Beer, Chris Vervaet, Ana Tavares Da Silva, Maunu Toiviainen, Jeroen Van Renterghem, Mikko Juuti, João A. Lopes, Jean Paul RemonAbstract: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 collected offline and Tablet properties determined with traditional analyzing methods. Partial Least Squares (PLS) regression was used to correlate spectral information to Tablet properties, but predictive models couldn't be established. Principal component analysis (PCA) was effectively used to distinguish theophylline concentrations and hydration levels and multiple linear regression (MLR) analysis allowed insight on how granulation parameters affect granule and Tablet properties.
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reduction of Tablet Weight variability by optimizing paddle speed in the forced feeder of a high speed rotary Tablet press
Drug Development and Industrial Pharmacy, 2015Co-Authors: Elisabeth Peeters, Thomas De Beer, Chris Vervaet, Jean Paul RemonAbstract:AbstractContext: Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release.Objective: The aim of this study was to investigate the influence of paddle speeds and fill depth at different Tableting speeds on the Weight and Weight variability of Tablets.Materials and methods: Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary Tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured.Results and discussion: Analysis of the DoE revealed that paddle speeds are of minor importance for Tablet Weight but significantly affect volume of powder inside the feeder in...
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Use of a continuous twin screw granulation and drying system during formulation development and process optimization
European Journal of Pharmaceutics and Biopharmaceutics, 2015Co-Authors: Jurgen Vercruysse, U. Delaet, I. Van Assche, Philippe Cappuyns, Margot Fonteyne, Thomas De Beer, E Peeters, Jean Paul Remon, Chris VervaetAbstract:Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and Tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P Tablet press (Tablet Weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1 h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as Tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1 h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating granule and Tablet quality attributes were obtained during the start-up phase of the 1 h run. For the single cell runs, granule and Tablet properties were comparable with results obtained during the second part of the 1 h run (after start-up). Although deviating granule quality (particle size distribution and Hausner ratio) was observed due to the divergent design of the ConsiGma™-1 unit and the ConsiGma™-25 system (horizontal set-up) used in this study, Tablet quality produced from granules processed with the ConsiGma™-1 system was predictive for Tablet quality obtained during continuous production using the ConsiGma™-25 system.
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Stability and repeatability of a continuous twin screw granulation and drying system
European Journal of Pharmaceutics and Biopharmaceutics, 2013Co-Authors: Jurgen Vercruysse, U. Delaet, Philippe Cappuyns, Jean Paul Remon, T. De Beer, I. Van Assche, F. Arata, G. Caporicci, Chris VervaetAbstract:Abstract The aim of this study was to investigate the process transfer of a commercially available product from the current batch fluid bed granulation and drying production method to an innovative continuously operating “from powder to Tablet” production line using twin screw granulation as an intermediate granulation step. By monitoring process outcomes (torque, water temperature at the granulator jacket inlet, differential pressure over the dryer filters, and temperature mill screen) and granule and Tablet quality in function of process time, the stability and repeatability during long production runs were determined. Three consecutive 5 h “from powder to Tablet” production runs were performed using the ConsiGma™-25 system (GEA Pharma Systems, Collette™, Wommelgem, Belgium). A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch, and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm and 800 rpm), granules were in-line blended with magnesium stearate and directly compressed using a Modul™ P Tablet press (Tablet Weight: 430 mg, main compression force: 12 kN). Granule (loss on drying, particle size distribution, friability, flow) and Tablet (Weight uniformity, hardness, thickness, friability, content uniformity, disintegration time, and dissolution) quality was evaluated in function of process time. For each of the logged process outcomes, a stabilization period was needed to reach steady-state conditions. Slightly deviating particle size distribution and friability results for milled granules were observed during start-up due to initial layering of the mill screen. However, no deviating Tablet quality was detected in function of process time. For multiple hours, granule and Tablet quality was constant in function of process time. Furthermore, process data trends were highly repeatable. Consequently, the ConsiGma™-25 system can be considered as a stable and repeatable system for the continuous production of Tablets via wet granulation.
Thomas De Beer - One of the best experts on this subject based on the ideXlab platform.
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Assessment and prediction of Tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy
Asian Journal of Pharmaceutical Sciences, 2016Co-Authors: Elisabeth Peeters, Jurgen Vercruysse, Thomas De Beer, Chris Vervaet, Ana Tavares Da Silva, Maunu Toiviainen, Jeroen Van Renterghem, Mikko Juuti, João A. Lopes, Jean Paul RemonAbstract: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 collected offline and Tablet properties determined with traditional analyzing methods. Partial Least Squares (PLS) regression was used to correlate spectral information to Tablet properties, but predictive models couldn't be established. Principal component analysis (PCA) was effectively used to distinguish theophylline concentrations and hydration levels and multiple linear regression (MLR) analysis allowed insight on how granulation parameters affect granule and Tablet properties.
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reduction of Tablet Weight variability by optimizing paddle speed in the forced feeder of a high speed rotary Tablet press
Drug Development and Industrial Pharmacy, 2015Co-Authors: Elisabeth Peeters, Thomas De Beer, Chris Vervaet, Jean Paul RemonAbstract:AbstractContext: Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release.Objective: The aim of this study was to investigate the influence of paddle speeds and fill depth at different Tableting speeds on the Weight and Weight variability of Tablets.Materials and methods: Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary Tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured.Results and discussion: Analysis of the DoE revealed that paddle speeds are of minor importance for Tablet Weight but significantly affect volume of powder inside the feeder in...
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Use of a continuous twin screw granulation and drying system during formulation development and process optimization
European Journal of Pharmaceutics and Biopharmaceutics, 2015Co-Authors: Jurgen Vercruysse, U. Delaet, I. Van Assche, Philippe Cappuyns, Margot Fonteyne, Thomas De Beer, E Peeters, Jean Paul Remon, Chris VervaetAbstract:Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and Tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P Tablet press (Tablet Weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1 h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as Tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1 h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating granule and Tablet quality attributes were obtained during the start-up phase of the 1 h run. For the single cell runs, granule and Tablet properties were comparable with results obtained during the second part of the 1 h run (after start-up). Although deviating granule quality (particle size distribution and Hausner ratio) was observed due to the divergent design of the ConsiGma™-1 unit and the ConsiGma™-25 system (horizontal set-up) used in this study, Tablet quality produced from granules processed with the ConsiGma™-1 system was predictive for Tablet quality obtained during continuous production using the ConsiGma™-25 system.