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Jean Paul Remon - One of the best experts on this subject based on the ideXlab platform.
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conceptual framework for model based analysis of residence time distribution in twin screw Granulation
European Journal of Pharmaceutical Sciences, 2015Co-Authors: Ashish Kumar, Jean Paul Remon, Jurgen Vercruysse, Valerie Vanhoorne, Maunu Toiviainen, Pierreemmanuel Panouillot, Mikko Juuti, Chris Vervaet, Krist V Gernaey, Thomas De BeerAbstract:Abstract 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 within each module where different Granulation rate processes dominate over others. Currently, experimental data is used to determine the residence time distributions. In this study, a conceptual model based on classical chemical engineering methods is proposed to better understand and simulate the residence time distribution in a TSG. The experimental data were compared with the proposed most suitable conceptual model to estimate the parameters of the model and to analyse and predict the effects of changes in number of kneading discs and their stagger angle, screw speed and powder feed rate on residence time. The study established that the kneading block in the screw configuration acts as a plug-flow zone inside the granulator. Furthermore, it was found that a balance between the throughput force and conveying rate is required to obtain a good axial mixing inside the twin-screw granulator. Although the Granulation behaviour is different for other excipients, the experimental data collection and modelling methods applied in this study are generic and can be adapted to other excipients.
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continuous twin screw Granulation influence of process variables on granule and tablet quality
European Journal of Pharmaceutics and Biopharmaceutics, 2012Co-Authors: Jurgen Vercruysse, Jean Paul Remon, Thomas De Beer, Cordoba D Diaz, Elisabeth Peeters, Margot Fonteyne, U Delaet, I Van Assche, Chris VervaetAbstract:Abstract The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw Granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, α-lactose monohydrate and PVP (ratio: 30/67.5/2.5, w/w) was granulated with demineralized water. Experiments were done using the high-shear wet Granulation module (based on twin screw Granulation) of the ConsiGma™-25 unit (a continuous tablet manufacturing system) for particle size enlargement. After drying, granules were compressed using a MODUL™ P tablet press (compression force: 10 kN, tablet diameter: 12 mm). Using a D-optimal experimental design, the effect of several process variables (throughput (10–25 kg/h), screw speed (600–950 rpm), screw configuration (number (2, 4, 6 and 12) and angle (30°, 60° and 90°) of kneading elements), barrel temperature (25–40 °C) and method of binder addition (dry versus wet)) on the Granulation process (torque and temperature increase in barrel wall), granule (particle size distribution, friability and flowability) and tablet (tensile strength, porosity, friability, disintegration time and dissolution) quality was evaluated. The results showed that the quality of granules and tablets can be optimized by adjusting specific process variables (number of kneading elements, barrel temperature and binder addition method) during a Granulation process using a continuous twin screw granulator.
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comparison of two twin screw extruders for continuous Granulation
European Journal of Pharmaceutics and Biopharmaceutics, 2009Co-Authors: Dejan Djuric, B Van Melkebeke, Jean Paul Remon, Peter Kleinebudde, Chris VervaetAbstract:Abstract A comparison was made between two twin-screw extruders (APV Baker and Leistritz Micro) used for continuous wet Granulation. Both extruders had similar screw configurations, based on the length-to-diameter ratio of the screws, existing out of a conveying zone of 20 D, i.e. 20 times the screw diameter and a Granulation zone of 4 D. The kneading blocks in the Granulation zone were 2.2 and 2.5 D for the Leistritz and APV extruders, respectively. An experimental design was used to investigate the influence of process parameters (total input rate and screw speed) and extruder type on granule and tablet quality. Dicalcium phosphate and α-lactose monohydrate were used as water-insoluble and water-soluble excipients, respectively. For dicalcium phosphate, the amount of fines (
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validation of a continuous Granulation process using a twin screw extruder
International Journal of Pharmaceutics, 2008Co-Authors: B Van Melkebeke, Chris Vervaet, Jean Paul RemonAbstract:Using twin-screw Granulation as particle size enlargement technique, the effect of modifying the screw configuration (number of mixing zones, configuration of kneading block) on granule quality, tablet properties and mixing efficiency was investigated. The amount of oversized agglomerates and yield was significantly influenced by the presence of an extra conveying element at the screw end. Changing the staggering angle of the kneading block significantly affected yield and granule friability. The 90° configuration resulted in a lower yield and granule friability. Disintegration time was the only tablet property significantly influenced by the screw configuration as disintegration was significantly faster when an extra conveying element was placed at the screw end. The influence of tracer addition method (wet vs. dry) on mixing efficiency inside the extruder barrel was investigated by means of different tracers: riboflavin (0.05%) suspended in the Granulation liquid and hydrochlorothiazide (2.5%) added separately as powder. Mixing efficiency in function of time and granule size (above and below 1400 μm) was tested using riboflavine sodium phosphate (0.05%) dissolved in the Granulation liquid. Since a good mixing efficiency was obtained independent of tracer addition method, tracer solubility, Granulation time and granule size, continuous Granulation using a twin-screw extruder was identified as a robust process.
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Twin screw Granulation as a simple and efficient tool for continuous wet Granulation.
International journal of pharmaceutics, 2004Co-Authors: E I Keleb, Chris Vervaet, A Vermeire, Jean Paul RemonAbstract:The modification of a twin screw extruder for continuous wet Granulation was investigated. Modification of the extruder setup as well as the screw design allowed the continuous wet Granulation of alpha-lactose monohydrate without the need of a wet sieving step. The robustness of twin screw Granulation was evaluated by studying the influence of processing parameters and formulation variables on the process performance and on the properties of alpha-lactose monohydrate granules and tablets. The process reproducibility during long term production was evaluated. Screw speed (200-450 rpm) and total input rate (5.5-9.5 kg/h) had no significant influence on the granule properties, while the water concentration during Granulation influenced the process as well as the granule properties. At a water concentration (calculated on wet granule basis) of 5.5-8.5%, continuous twin screw Granulation of alpha-lactose monohydrate 200 M was feasible and the granules obtained had good properties. PVP addition mainly affected tablet properties. Tablets made from granules containing 2.5% PVP had a tensile strength above 0.94 MPa, a friability below 1% and a disintegration time ranging between 495 and 576 s. Tablets containing hydrochlorothiazide complied with the dissolution requirements as 60% was released after 5 and 15 min from tablets without PVP and with 2.5% PVP, respectively. No problems were observed during continuous twin screw Granulation over a period of 8h and the granule and tablet properties were reproducible throughout the process. These results indicated that twin screw Granulation is an efficient tool for continuous wet Granulation.
Chris Vervaet - One of the best experts on this subject based on the ideXlab platform.
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conceptual framework for model based analysis of residence time distribution in twin screw Granulation
European Journal of Pharmaceutical Sciences, 2015Co-Authors: Ashish Kumar, Jean Paul Remon, Jurgen Vercruysse, Valerie Vanhoorne, Maunu Toiviainen, Pierreemmanuel Panouillot, Mikko Juuti, Chris Vervaet, Krist V Gernaey, Thomas De BeerAbstract:Abstract 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 within each module where different Granulation rate processes dominate over others. Currently, experimental data is used to determine the residence time distributions. In this study, a conceptual model based on classical chemical engineering methods is proposed to better understand and simulate the residence time distribution in a TSG. The experimental data were compared with the proposed most suitable conceptual model to estimate the parameters of the model and to analyse and predict the effects of changes in number of kneading discs and their stagger angle, screw speed and powder feed rate on residence time. The study established that the kneading block in the screw configuration acts as a plug-flow zone inside the granulator. Furthermore, it was found that a balance between the throughput force and conveying rate is required to obtain a good axial mixing inside the twin-screw granulator. Although the Granulation behaviour is different for other excipients, the experimental data collection and modelling methods applied in this study are generic and can be adapted to other excipients.
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continuous twin screw Granulation influence of process variables on granule and tablet quality
European Journal of Pharmaceutics and Biopharmaceutics, 2012Co-Authors: Jurgen Vercruysse, Jean Paul Remon, Thomas De Beer, Cordoba D Diaz, Elisabeth Peeters, Margot Fonteyne, U Delaet, I Van Assche, Chris VervaetAbstract:Abstract The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw Granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, α-lactose monohydrate and PVP (ratio: 30/67.5/2.5, w/w) was granulated with demineralized water. Experiments were done using the high-shear wet Granulation module (based on twin screw Granulation) of the ConsiGma™-25 unit (a continuous tablet manufacturing system) for particle size enlargement. After drying, granules were compressed using a MODUL™ P tablet press (compression force: 10 kN, tablet diameter: 12 mm). Using a D-optimal experimental design, the effect of several process variables (throughput (10–25 kg/h), screw speed (600–950 rpm), screw configuration (number (2, 4, 6 and 12) and angle (30°, 60° and 90°) of kneading elements), barrel temperature (25–40 °C) and method of binder addition (dry versus wet)) on the Granulation process (torque and temperature increase in barrel wall), granule (particle size distribution, friability and flowability) and tablet (tensile strength, porosity, friability, disintegration time and dissolution) quality was evaluated. The results showed that the quality of granules and tablets can be optimized by adjusting specific process variables (number of kneading elements, barrel temperature and binder addition method) during a Granulation process using a continuous twin screw granulator.
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comparison of two twin screw extruders for continuous Granulation
European Journal of Pharmaceutics and Biopharmaceutics, 2009Co-Authors: Dejan Djuric, B Van Melkebeke, Jean Paul Remon, Peter Kleinebudde, Chris VervaetAbstract:Abstract A comparison was made between two twin-screw extruders (APV Baker and Leistritz Micro) used for continuous wet Granulation. Both extruders had similar screw configurations, based on the length-to-diameter ratio of the screws, existing out of a conveying zone of 20 D, i.e. 20 times the screw diameter and a Granulation zone of 4 D. The kneading blocks in the Granulation zone were 2.2 and 2.5 D for the Leistritz and APV extruders, respectively. An experimental design was used to investigate the influence of process parameters (total input rate and screw speed) and extruder type on granule and tablet quality. Dicalcium phosphate and α-lactose monohydrate were used as water-insoluble and water-soluble excipients, respectively. For dicalcium phosphate, the amount of fines (
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validation of a continuous Granulation process using a twin screw extruder
International Journal of Pharmaceutics, 2008Co-Authors: B Van Melkebeke, Chris Vervaet, Jean Paul RemonAbstract:Using twin-screw Granulation as particle size enlargement technique, the effect of modifying the screw configuration (number of mixing zones, configuration of kneading block) on granule quality, tablet properties and mixing efficiency was investigated. The amount of oversized agglomerates and yield was significantly influenced by the presence of an extra conveying element at the screw end. Changing the staggering angle of the kneading block significantly affected yield and granule friability. The 90° configuration resulted in a lower yield and granule friability. Disintegration time was the only tablet property significantly influenced by the screw configuration as disintegration was significantly faster when an extra conveying element was placed at the screw end. The influence of tracer addition method (wet vs. dry) on mixing efficiency inside the extruder barrel was investigated by means of different tracers: riboflavin (0.05%) suspended in the Granulation liquid and hydrochlorothiazide (2.5%) added separately as powder. Mixing efficiency in function of time and granule size (above and below 1400 μm) was tested using riboflavine sodium phosphate (0.05%) dissolved in the Granulation liquid. Since a good mixing efficiency was obtained independent of tracer addition method, tracer solubility, Granulation time and granule size, continuous Granulation using a twin-screw extruder was identified as a robust process.
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Twin screw Granulation as a simple and efficient tool for continuous wet Granulation.
International journal of pharmaceutics, 2004Co-Authors: E I Keleb, Chris Vervaet, A Vermeire, Jean Paul RemonAbstract:The modification of a twin screw extruder for continuous wet Granulation was investigated. Modification of the extruder setup as well as the screw design allowed the continuous wet Granulation of alpha-lactose monohydrate without the need of a wet sieving step. The robustness of twin screw Granulation was evaluated by studying the influence of processing parameters and formulation variables on the process performance and on the properties of alpha-lactose monohydrate granules and tablets. The process reproducibility during long term production was evaluated. Screw speed (200-450 rpm) and total input rate (5.5-9.5 kg/h) had no significant influence on the granule properties, while the water concentration during Granulation influenced the process as well as the granule properties. At a water concentration (calculated on wet granule basis) of 5.5-8.5%, continuous twin screw Granulation of alpha-lactose monohydrate 200 M was feasible and the granules obtained had good properties. PVP addition mainly affected tablet properties. Tablets made from granules containing 2.5% PVP had a tensile strength above 0.94 MPa, a friability below 1% and a disintegration time ranging between 495 and 576 s. Tablets containing hydrochlorothiazide complied with the dissolution requirements as 60% was released after 5 and 15 min from tablets without PVP and with 2.5% PVP, respectively. No problems were observed during continuous twin screw Granulation over a period of 8h and the granule and tablet properties were reproducible throughout the process. These results indicated that twin screw Granulation is an efficient tool for continuous wet Granulation.
Michael Thompso - One of the best experts on this subject based on the ideXlab platform.
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examining drug hydrophobicity in continuous wet Granulation within a twin screw extruder
International Journal of Pharmaceutics, 2015Co-Authors: Michael Thompso, Kevi P OdonnellAbstract:Abstract The influence of active pharmaceutical ingredient (API) hydrophobicity on continuous wet Granulation was studied in twin screw Granulation utilizing foamed binder delivery. The APIs examined were caffeine, acetaminophen, ibuprofen and griseofulvin and the drug load was maintained constant at 15 wt%. In order to understand the impact of these APIs on the Granulation process, API and binder distribution, particle size, porosity, and fracture strength were analyzed on samples collected along the screw length. It was found that the API and binder distributions were uniform along the screws regardless of the hydrophobicity of the formulation, in contrast to literature results with liquid injection. The absence of de-mixing of the hydrophobic ingredient was hypothesized to be a result of the high spread-to-soak ratio of a foamed binder that ‘cages’ those particles within the mass of local hydrophilic solids.
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wet Granulation in a twin screw extruder implications of screw design
Journal of Pharmaceutical Sciences, 2010Co-Authors: Michael ThompsoAbstract:Wet Granulation in twin-screw extrusion machinery is an attractive technology for the continuous processing of pharmaceuticals. The performance of this machinery is integrally tied to its screw design yet little fundamental knowledge exists in this emerging field for Granulation to intelligently create, troubleshoot, and scale-up such processes. This study endeavored to systematically examine the influence of different commercially available screw elements on the flow behavior and Granulation mechanics of lactose monohydrate saturated at low concentration (5-12%, w/w) with an aqueous polyvinyl-pyrrolidone binder. The results of the work showed that current screw elements could be successfully incorporated into designs for wet Granulation, to tailor the particle size as well as particle shape of an agglomerate product. Conveying elements for cohesive granular flows were shown to perform similar to their use in polymer processing, as effective transport units with low specific mechanical energy input. The conveying zones provided little significant change to the particle size or shape, though the degree of channel fill in these sections had a significant influence on the more energy-intensive mixing elements studied. The standard mixing elements for this machine, kneading blocks and comb mixers, were found to be effective for generating coarser particles, though their mechanisms of Granulation differed significantly.
Jurgen Vercruysse - One of the best experts on this subject based on the ideXlab platform.
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conceptual framework for model based analysis of residence time distribution in twin screw Granulation
European Journal of Pharmaceutical Sciences, 2015Co-Authors: Ashish Kumar, Jean Paul Remon, Jurgen Vercruysse, Valerie Vanhoorne, Maunu Toiviainen, Pierreemmanuel Panouillot, Mikko Juuti, Chris Vervaet, Krist V Gernaey, Thomas De BeerAbstract:Abstract 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 within each module where different Granulation rate processes dominate over others. Currently, experimental data is used to determine the residence time distributions. In this study, a conceptual model based on classical chemical engineering methods is proposed to better understand and simulate the residence time distribution in a TSG. The experimental data were compared with the proposed most suitable conceptual model to estimate the parameters of the model and to analyse and predict the effects of changes in number of kneading discs and their stagger angle, screw speed and powder feed rate on residence time. The study established that the kneading block in the screw configuration acts as a plug-flow zone inside the granulator. Furthermore, it was found that a balance between the throughput force and conveying rate is required to obtain a good axial mixing inside the twin-screw granulator. Although the Granulation behaviour is different for other excipients, the experimental data collection and modelling methods applied in this study are generic and can be adapted to other excipients.
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visualization and understanding of the Granulation liquid mixing and distribution during continuous twin screw Granulation using nir chemical imaging
European Journal of Pharmaceutics and Biopharmaceutics, 2014Co-Authors: Jurgen Vercruysse, Mikko Juuti, Maunu Toiviaine, Margo Fonteyne, Niko Helkimo, Jarkko Ketolaine, Urbain Alfons C Delae, Ivo Van Assche, Jean Paul Remo, Chris VervaeAbstract:Abstract Over the last decade, there has been increased interest in the application of twin screw Granulation as a continuous wet Granulation technique for pharmaceutical drug formulations. However, the mixing of Granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw Granulation is not yet fully understood. Therefore, this study aims at visualizing the Granulation liquid mixing and distribution during continuous twin screw Granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the Granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of Granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the Granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw Granulation system.
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continuous twin screw Granulation influence of process variables on granule and tablet quality
European Journal of Pharmaceutics and Biopharmaceutics, 2012Co-Authors: Jurgen Vercruysse, Jean Paul Remon, Thomas De Beer, Cordoba D Diaz, Elisabeth Peeters, Margot Fonteyne, U Delaet, I Van Assche, Chris VervaetAbstract:Abstract The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw Granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, α-lactose monohydrate and PVP (ratio: 30/67.5/2.5, w/w) was granulated with demineralized water. Experiments were done using the high-shear wet Granulation module (based on twin screw Granulation) of the ConsiGma™-25 unit (a continuous tablet manufacturing system) for particle size enlargement. After drying, granules were compressed using a MODUL™ P tablet press (compression force: 10 kN, tablet diameter: 12 mm). Using a D-optimal experimental design, the effect of several process variables (throughput (10–25 kg/h), screw speed (600–950 rpm), screw configuration (number (2, 4, 6 and 12) and angle (30°, 60° and 90°) of kneading elements), barrel temperature (25–40 °C) and method of binder addition (dry versus wet)) on the Granulation process (torque and temperature increase in barrel wall), granule (particle size distribution, friability and flowability) and tablet (tensile strength, porosity, friability, disintegration time and dissolution) quality was evaluated. The results showed that the quality of granules and tablets can be optimized by adjusting specific process variables (number of kneading elements, barrel temperature and binder addition method) during a Granulation process using a continuous twin screw granulator.
Abu T M Serajuddi - One of the best experts on this subject based on the ideXlab platform.
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development and optimization of a wet Granulation process at elevated temperature for a poorly compactible drug using twin screw extruder for continuous manufacturing
Journal of Pharmaceutical Sciences, 2017Co-Authors: Anuprabha Meena, Divyaka Desai, Abu T M SerajuddiAbstract:The objective of this study was to enhance tabletability of a poorly compactible drug, acetaminophen, by wet Granulation using twin screw extruder at high temperature. It was desired that there would be minimum amounts of excipients used and the granules obtained after extrusion would be dry and fall within a size range suitable for tableting without any further processing. Mixtures of acetaminophen (95%) with binders (5% povidone or partially pregelatinized starch) were wet granulated through twin screw extruder at 70°C by adding 7% w/w water. The process had a short Granulation time ( 90% granules in the size range of 125 to 1000 μm ( 1.7 MPa, which was superior to that of tablets prepared by conventional high shear wet Granulation. As the granules could be extruded continuously and did not require drying and milling, the method was amenable to continuous processing.
