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Jean Paul Remon - One of the best experts on this subject based on the ideXlab platform.
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production of pellets via extrusion Spheronisation without the incorporation of microcrystalline cellulose a critical review
European Journal of Pharmaceutics and Biopharmaceutics, 2009Co-Authors: Aleksandra Dukicott, Markus Thommes, Peter Kleinebudde, Jean Paul Remon, Chris VervaetAbstract:Abstract Microcrystalline cellulose (MCC) is the golden standard to manufacture spherical particles (pellets) via extrusion–Spheronisation since wetted microcrystalline cellulose has the proper rheological properties, cohesiveness and plasticity to yield strong and spherical particles. However, microcrystalline cellulose is not universally applicable due to a number of limitations: prolonged drug release of poorly soluble drugs, chemical incompatibility with specific drugs, drug adsorption onto MCC fibers. Hence, several products have been evaluated to explore their application as extrusion–Spheronisation aid, aiming to avoid the disadvantages of MCC and to provide a broad application platform for extrusion–Spheronisation: powdered cellulose, starch, chitosan, kappa-carrageenan, pectinic acid, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, polyethylene oxide, cross-linked polyvinylpyrrolidone, glycerol monostearate. To determine the true potential of the proposed alternatives for MCC this review critically discusses the properties of the different materials and the quality of the resulting pellets in relation to the properties required for an ideal extrusion–Spheronisation aid.
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development of starch based pellets via extrusion Spheronisation
European Journal of Pharmaceutics and Biopharmaceutics, 2007Co-Authors: Aleksandra Dukic, Raoul Mens, Paul B. Foreman, Peter Adriaensens, Jan Gelan, Jean Paul Remon, Chris VervaetAbstract:Abstract A modified starch (high-amylose, crystalline and resistant starch) was evaluated as an alternative excipient to microcrystalline cellulose for pellets prepared via extrusion/Spheronisation. Theophylline anhydrous (25%, w/w) was used as a model drug. A binder was necessary to obtain an acceptable yield and the addition of sorbitol improved the surface properties of the pellets. A surface response design with three formulation variables (binder, sorbitol and water level) and one process variable (Spheronisation speed) was used to optimise the process and to evaluate pellet yield, sphericity (aspect ratio and two-dimensional shape factor, e R ), size (mean Feret diameter), friability and disintegration properties. Mixer torque rheometry and solid-state NMR revealed a significant influence of sorbitol on wet mass consistency and pellet properties. A high pellet yield (>90%), acceptable sphericity (AR
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Development of starch-based pellets via extrusion/Spheronisation.
European Journal of Pharmaceutics and Biopharmaceutics, 2006Co-Authors: Aleksandra Dukic, Raoul Mens, Paul B. Foreman, Peter Adriaensens, Jan Gelan, Jean Paul Remon, Chris VervaetAbstract:Abstract A modified starch (high-amylose, crystalline and resistant starch) was evaluated as an alternative excipient to microcrystalline cellulose for pellets prepared via extrusion/Spheronisation. Theophylline anhydrous (25%, w/w) was used as a model drug. A binder was necessary to obtain an acceptable yield and the addition of sorbitol improved the surface properties of the pellets. A surface response design with three formulation variables (binder, sorbitol and water level) and one process variable (Spheronisation speed) was used to optimise the process and to evaluate pellet yield, sphericity (aspect ratio and two-dimensional shape factor, e R ), size (mean Feret diameter), friability and disintegration properties. Mixer torque rheometry and solid-state NMR revealed a significant influence of sorbitol on wet mass consistency and pellet properties. A high pellet yield (>90%), acceptable sphericity (AR
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Evaluation of extrusion/Spheronisation, layering and compaction for the preparation of an oral, multi-particulate formulation of viable, hIL-10 producing Lactococcus lactis.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2005Co-Authors: Nathalie Huyghebaert, An Vermeire, Sabine Neirynck, Lothar Steidler, Eric Remaut, Jean Paul RemonAbstract:Three formulation techniques were compared in order to develop a multi-particulate formulation of viable, interleukin-10 producing Lactococcus lactis Thy12. First, freeze-dried L. lactis was compacted into mini-tablets. Next, liquid L. lactis culture was used as the granulation fluid for the production of pellets by extrusion/Spheronisation. Finally, liquid L. lactis culture was layered on inert pellets as an alternative technique for the production of pellets. L. lactis viability and interleukin-10 production was evaluated. Viability dropped to 15.7% after compaction of freeze-dried L. lactis and to 1.0% after pelletisation of liquid L. lactis by extrusion/Spheronisation. The viability in the mini-tablets and pellets, stored for 1 week at RT and 10% RH was reduced to 23 and 0.5% of initial viability, respectively. Storage for 1 week at RT and 60% RH resulted in complete loss of viability. Layering of L. lactis on inert pellets resulted in low viability (4.86%), but 1 week after storage at RT and 10% RH, 68% of initial viability was maintained. Increasing product temperature and cell density of L. lactis in the layering suspension did not significantly change viability after layering and storage. Interleukin-10 production capacity of L. lactis Thy12 was maintained after layering.
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evaluation of extrusion Spheronisation layering and compaction for the preparation of an oral multi particulate formulation of viable hil 10 producing lactococcus lactis
European Journal of Pharmaceutics and Biopharmaceutics, 2005Co-Authors: Nathalie Huyghebaert, An Vermeire, Sabine Neirynck, Lothar Steidler, Eric Remaut, Jean Paul RemonAbstract:Three formulation techniques were compared in order to develop a multi-particulate formulation of viable, interleukin-10 producing Lactococcus lactis Thy12. First, freeze-dried L. lactis was compacted into mini-tablets. Next, liquid L. lactis culture was used as the granulation fluid for the production of pellets by extrusion/Spheronisation. Finally, liquid L. lactis culture was layered on inert pellets as an alternative technique for the production of pellets. L. lactis viability and interleukin-10 production was evaluated. Viability dropped to 15.7% after compaction of freeze-dried L. lactis and to 1.0% after pelletisation of liquid L. lactis by extrusion/Spheronisation. The viability in the mini-tablets and pellets, stored for 1 week at RT and 10% RH was reduced to 23 and 0.5% of initial viability, respectively. Storage for 1 week at RT and 60% RH resulted in complete loss of viability. Layering of L. lactis on inert pellets resulted in low viability (4.86%), but 1 week after storage at RT and 10% RH, 68% of initial viability was maintained. Increasing product temperature and cell density of L. lactis in the layering suspension did not significantly change viability after layering and storage. Interleukin-10 production capacity of L. lactis Thy12 was maintained after layering.
Peter Kleinebudde - One of the best experts on this subject based on the ideXlab platform.
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a data mining approach to optimize pellets manufacturing process based on a decision tree algorithm
European Journal of Pharmaceutical Sciences, 2015Co-Authors: Joanna Ronowicz, Markus Thommes, Peter Kleinebudde, Jerzy KrysinskiAbstract:The present study is focused on the thorough analysis of cause-effect relationships between pellet formulation characteristics (pellet composition as well as process parameters) and the selected quality attribute of the final product. The shape using the aspect ratio value expressed the quality of pellets. A data matrix for chemometric analysis consisted of 224 pellet formulations performed by means of eight different active pharmaceutical ingredients and several various excipients, using different extrusion/spheronization process conditions. The data set contained 14 input variables (both formulation and process variables) and one output variable (pellet aspect ratio). A tree regression algorithm consistent with the Quality by Design concept was applied to obtain deeper understanding and knowledge of formulation and process parameters affecting the final pellet sphericity. The clear interpretable set of decision rules were generated. The spehronization speed, spheronization time, number of holes and water content of extrudate have been recognized as the key factors influencing pellet aspect ratio. The most spherical pellets were achieved by using a large number of holes during extrusion, a high spheronizer speed and longer time of spheronization. The described data mining approach enhances knowledge about pelletization process and simultaneously facilitates searching for the optimal process conditions which are necessary to achieve ideal spherical pellets, resulting in good flow characteristics. This data mining approach can be taken into consideration by industrial formulation scientists to support rational decision making in the field of pellets technology.
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Spheronisation mechanism of MCC II-based pellets
Powder Technology, 2013Co-Authors: Cornelia Krueger, Markus Thommes, Peter KleinebuddeAbstract:Abstract Microcrystalline cellulose II (MCC II) – a polymorph of commonly used MCC I – was introduced as new pelletisation aid in wet-extrusion/Spheronisation. Preliminary investigations suggested that the Spheronisation mechanism of MCC II-based pellets differs from the known mechanism of MCC I. Therefore the Spheronisation mechanism of MCC II-based pellets was investigated and compared to that of MCC I. The study dealt with the effect of spheroniser load as well as Spheronisation speed and time on the pellet properties of shape (aspect ratio), size (equivalent diameter), weight, porosity, size distribution (10%-interval) and yield (fine fraction) of MCC II-based formulations. The parameters were systematically varied in a 3 3 full factorial design; Furthermore Spheronisation time experiments with Spheronisation times from 10 s to 15 min (13 steps) were conducted. For this purpose mixtures with 20% MCC II and 80% lactose or chloramphenicol were chosen. A mixture of 20% MCC I and 80% lactose served as comparison. Regarding the MCC II-based pellets all investigated pellet properties were significantly influenced by Spheronisation speed and time, spheroniser load showed nearly no influence. Aspect ratio, 10%-interval and porosity decreased continuously throughout the entire Spheronisation process. After a slight decrease, pellet weight and equivalent diameter increased during Spheronisation. On the contrary the fine fraction decreased during Spheronisation after passing a maximum in the first minutes of Spheronisation. MCC I-based pellets behaved differently during Spheronisation: Pellet weight remained nearly constant during Spheronisation and the equivalent diameter decreased; The fine fraction was lower compared to that of the MCC II-based pellets. The higher fine fraction of MCC II could partly explain this result as the fine fraction layered on the pellets. However, the fine fraction was too low to explain the complete weight gain. Therefore, a new Spheronisation mechanism for MCC-II based pellets was proposed: It was suspected that small pellets abraded during processing and layered on the other pellets. This presumption was supported by the high increase of the 10%-interval of the MCC II-based pellets during Spheronisation indicating a narrowing of the size distribution; The improvement was less pronounced for the MCC I-based pellets. MCC II behaves in a different manner than MCC I in Spheronisation: A deeper insight into the Spheronisation of MCC II-based pellets was obtained providing a new pelletisation mechanism that is the basis to control and influence the Spheronisation process of MCC II-based pellets.
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production of pellets via extrusion Spheronisation without the incorporation of microcrystalline cellulose a critical review
European Journal of Pharmaceutics and Biopharmaceutics, 2009Co-Authors: Aleksandra Dukicott, Markus Thommes, Peter Kleinebudde, Jean Paul Remon, Chris VervaetAbstract:Abstract Microcrystalline cellulose (MCC) is the golden standard to manufacture spherical particles (pellets) via extrusion–Spheronisation since wetted microcrystalline cellulose has the proper rheological properties, cohesiveness and plasticity to yield strong and spherical particles. However, microcrystalline cellulose is not universally applicable due to a number of limitations: prolonged drug release of poorly soluble drugs, chemical incompatibility with specific drugs, drug adsorption onto MCC fibers. Hence, several products have been evaluated to explore their application as extrusion–Spheronisation aid, aiming to avoid the disadvantages of MCC and to provide a broad application platform for extrusion–Spheronisation: powdered cellulose, starch, chitosan, kappa-carrageenan, pectinic acid, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, polyethylene oxide, cross-linked polyvinylpyrrolidone, glycerol monostearate. To determine the true potential of the proposed alternatives for MCC this review critically discusses the properties of the different materials and the quality of the resulting pellets in relation to the properties required for an ideal extrusion–Spheronisation aid.
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cross linking of amidated low methoxylated pectin with calcium during extrusion Spheronisation effect on particle size and shape
Chemical Engineering Science, 2005Co-Authors: Sverre Arne Sande, Ingunn Tho, Peter KleinebuddeAbstract:Granulation and pelletisation by wet extrusion/Spheronisation is a well-known technique for particle design in the pharmaceutical industry. The objective of this study was to evaluate the use of amidated low-methoxylated (LM) pectin as an excipient for pelletisation by extrusion/Spheronisation. The influence of degree of amidation of pectin (14%, 18% and 24%) and concentration of added calcium ions (0%, 5%, 12% w/w) on the shape and size of pectin pellets was investigated. The chosen approach was to aim at cross-linking during processing which could be obtained by adding calcium ions to the amidated pectin in the powder mixture and perform granulation/extrusion with water. Addition of calcium ions was expected to reduce the solubility and swelling of pectin during processing, and, consequently, the roundness of the pectin pellets should be improved. Both the degree of amidation and the concentration of added calcium ions as well as the interaction between the two were identified as significant factors in preparation of spherical pellets. The results suggest that the egg-box model alone cannot describe the cross-linking between amidated LM pectin and calcium ions, and it is proposed that the amid group itself plays an important role in the system.
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Cross-linking of amidated low-methoxylated pectin with calcium during extrusion/Spheronisation: Effect on particle size and shape
Chemical Engineering Science, 2005Co-Authors: Ingunn Tho, Sverre Arne Sande, Peter KleinebuddeAbstract:Granulation and pelletisation by wet extrusion/Spheronisation is a well-known technique for particle design in the pharmaceutical industry. The objective of this study was to evaluate the use of amidated low-methoxylated (LM) pectin as an excipient for pelletisation by extrusion/Spheronisation. The influence of degree of amidation of pectin (14%, 18% and 24%) and concentration of added calcium ions (0%, 5%, 12% w/w) on the shape and size of pectin pellets was investigated. The chosen approach was to aim at cross-linking during processing which could be obtained by adding calcium ions to the amidated pectin in the powder mixture and perform granulation/extrusion with water. Addition of calcium ions was expected to reduce the solubility and swelling of pectin during processing, and, consequently, the roundness of the pectin pellets should be improved. Both the degree of amidation and the concentration of added calcium ions as well as the interaction between the two were identified as significant factors in preparation of spherical pellets. The results suggest that the egg-box model alone cannot describe the cross-linking between amidated LM pectin and calcium ions, and it is proposed that the amid group itself plays an important role in the system.
Chris Vervaet - One of the best experts on this subject based on the ideXlab platform.
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The use of partially hydrolysed polyvinyl alcohol for the production of high drug-loaded sustained release pellets via extrusion-Spheronisation and coating: In vitro and in vivo evaluation.
International journal of pharmaceutics, 2016Co-Authors: G Verstraete, W De Jaeghere, J Vercruysse, W Grymonpré, V Vanhoorne, F Stauffer, T De Beer, A Bezuijen, J P Remon, Chris VervaetAbstract:Partially hydrolysed polyvinyl alcohol (PVA) was evaluated as a pelletisation aid for the production of pellets with a high acetaminophen and metformin hydrochloride concentration (>70%, w/w). Mixtures with varying drug concentration and PVA/microcrystalline cellulose (MCC) ratios were processed via extrusion-Spheronisation, either after addition of PVA as a dry powder or as an aqueous solution. Finally, high drug- loaded metformin pellets were coated with a methacrylic acid copolymer (Eudragit™ NM 30D) and evaluated for their sustained release potency in vitro and in vivo. The plasticity index of the wet mass increased by the addition of PVA to the formulation, which resulted in enhanced extrusion-Spheronisation properties, even at a high drug load. Although the MCC concentration was successfully lowered by adding PVA, the inclusion of MCC in the formulation was essential to overcome problems related to the tackiness effect of PVA during extrusion. Overall, wet addition of PVA was superior to dry addition, as pellets with a higher mechanical strength and narrower particle size distribution were obtained. Pellets containing 87% (w/w) metformin hydrochloride were successfully layered with 20% (w/w) coating material, yielding sustained release pellets with a final drug load of 70% (w/w). In addition, the sustained release characteristics of the PVA-based pellets with a high drug content were confirmed in vivo as no difference with the Glucophage™ SR reference formulation was observed.
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production of pellets via extrusion Spheronisation without the incorporation of microcrystalline cellulose a critical review
European Journal of Pharmaceutics and Biopharmaceutics, 2009Co-Authors: Aleksandra Dukicott, Markus Thommes, Peter Kleinebudde, Jean Paul Remon, Chris VervaetAbstract:Abstract Microcrystalline cellulose (MCC) is the golden standard to manufacture spherical particles (pellets) via extrusion–Spheronisation since wetted microcrystalline cellulose has the proper rheological properties, cohesiveness and plasticity to yield strong and spherical particles. However, microcrystalline cellulose is not universally applicable due to a number of limitations: prolonged drug release of poorly soluble drugs, chemical incompatibility with specific drugs, drug adsorption onto MCC fibers. Hence, several products have been evaluated to explore their application as extrusion–Spheronisation aid, aiming to avoid the disadvantages of MCC and to provide a broad application platform for extrusion–Spheronisation: powdered cellulose, starch, chitosan, kappa-carrageenan, pectinic acid, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, polyethylene oxide, cross-linked polyvinylpyrrolidone, glycerol monostearate. To determine the true potential of the proposed alternatives for MCC this review critically discusses the properties of the different materials and the quality of the resulting pellets in relation to the properties required for an ideal extrusion–Spheronisation aid.
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development of starch based pellets via extrusion Spheronisation
European Journal of Pharmaceutics and Biopharmaceutics, 2007Co-Authors: Aleksandra Dukic, Raoul Mens, Paul B. Foreman, Peter Adriaensens, Jan Gelan, Jean Paul Remon, Chris VervaetAbstract:Abstract A modified starch (high-amylose, crystalline and resistant starch) was evaluated as an alternative excipient to microcrystalline cellulose for pellets prepared via extrusion/Spheronisation. Theophylline anhydrous (25%, w/w) was used as a model drug. A binder was necessary to obtain an acceptable yield and the addition of sorbitol improved the surface properties of the pellets. A surface response design with three formulation variables (binder, sorbitol and water level) and one process variable (Spheronisation speed) was used to optimise the process and to evaluate pellet yield, sphericity (aspect ratio and two-dimensional shape factor, e R ), size (mean Feret diameter), friability and disintegration properties. Mixer torque rheometry and solid-state NMR revealed a significant influence of sorbitol on wet mass consistency and pellet properties. A high pellet yield (>90%), acceptable sphericity (AR
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Development of starch-based pellets via extrusion/Spheronisation.
European Journal of Pharmaceutics and Biopharmaceutics, 2006Co-Authors: Aleksandra Dukic, Raoul Mens, Paul B. Foreman, Peter Adriaensens, Jan Gelan, Jean Paul Remon, Chris VervaetAbstract:Abstract A modified starch (high-amylose, crystalline and resistant starch) was evaluated as an alternative excipient to microcrystalline cellulose for pellets prepared via extrusion/Spheronisation. Theophylline anhydrous (25%, w/w) was used as a model drug. A binder was necessary to obtain an acceptable yield and the addition of sorbitol improved the surface properties of the pellets. A surface response design with three formulation variables (binder, sorbitol and water level) and one process variable (Spheronisation speed) was used to optimise the process and to evaluate pellet yield, sphericity (aspect ratio and two-dimensional shape factor, e R ), size (mean Feret diameter), friability and disintegration properties. Mixer torque rheometry and solid-state NMR revealed a significant influence of sorbitol on wet mass consistency and pellet properties. A high pellet yield (>90%), acceptable sphericity (AR
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Extrusion-Spheronisation A literature review
International Journal of Pharmaceutics, 1995Co-Authors: Chris Vervaet, L. Baert, Jean Paul RemonAbstract:Abstract This review article deals with the aspects of the extrusion-Spheronisation process. The different steps in the production process of pellets are described. In a second part the parameters which can influence the pellet quality are discussed. Finally, an overview of the methods available for analysis of the quality of the pellets is given.
S L Rough - One of the best experts on this subject based on the ideXlab platform.
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Influence of plate surface protuberance size and shape on the production of pellets by extrusion-Spheronisation
Chemical Engineering Research & Design, 2016Co-Authors: Yanzhong Li, Jianfeng Xing, S L Rough, David I. WilsonAbstract:Abstract The influence of spheroniser plate surface protuberance geometry on pellets produced from Spheronisation of paste extrudates was investigated using a model paste material (45 wt% microcrystalline cellulose/water). Four cross-hatched pattern plates of different dimensions and/or shape of the surface protuberances were studied in terms of their effect on pellet water content, Spheronisation yield, pellet size and shape distributions, and surface morphology. In addition, the effect of the relative size of extrudates to protuberances was investigated by comparing pellets generated from 1 and 2 mm diameter extrudates. In this study, all the plates have the same groove line arrangement but differ in surface protuberance dimensions and/or shape, and so the focus differs from that of Michie et al. (2012) who investigated plates of different groove line arrangement. For all pellets the water content decreased with Spheronisation time, more so for samples made from 2 mm extrudates. A systematic effect of protuberance geometry on the product yield (a measure of losses due to fines) was evident for both extrudate sizes, with yields decreasing in the order (large studs), (pyramidal), (saw-toothed), and (small studs). Analysis of two-dimensional images of dried pellets indicated that the 2 mm diameter extrudates generated pellets with narrower size distributions and better shape quality parameters (aspect ratio and circularity). This was confirmed via SEM images showing the surface morphology. The results indicate that the size of extrudates relative to the plate features is important and should be investigated further.
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Experimental validation of a dimensional analysis of Spheronisation of cylindrical extrudates
Powder Technology, 2016Co-Authors: J Parkin, S L Rough, Ks Widjaja, Mp Bryan, D.i. WilsonAbstract:Abstract Extrusion–Spheronisation is a widely used technique for the manufacture of pellets with high sphericity and narrow size distribution. A dimensionless framework for describing the evolution of pellet shape with Spheronisation time is presented for the first time and is validated using new experimental data obtained with two families of materials: (i) microcrystalline cellulose (MCC)/water-based pastes with loadings of up to 15 wt% calcium carbonate, representing a ‘hard’ active pharmaceutical ingredient, and (ii) a lactose/MCC/water paste. The dimensional analysis of the pellet rounding stage identified the paste density and bulk yield strength, σ Y , as scaling quantities: σ Y was measured in separate extrusion tests and found to increase with increasing carbonate content. Higher paste strength gave longer Spheronisation times and less spherical pellets for a given set of Spheronisation conditions. The pellet aspect ratio was found to increase in a linear manner with the logarithm of Spheronisation time, progressing towards an asymptotic final value. This behaviour, which is evident in old data sets (e.g. Bryan et al. [1]) but has not been discussed previously, is compared with two simple models. High speed imaging was also used to examine the collision behaviour of pellets during the breakage and rounding stages in Spheronisation. This confirmed that the rounding phase was the rate-determining step. The velocities of a number of tracked pellets were consistently lower than the tip speed of the rotating friction plate, confirming previous findings in studies of beds of rotating pellets.
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Stages in Spheronisation: evolution of pellet size and shape during Spheronisation of microcrystalline cellulose-based paste extrudates
Powder Technology, 2015Co-Authors: Mp Bryan, S L Rough, Ln Atherton, S Duffield, D.i. WilsonAbstract:Abstract The stages of extrudate breakup and rounding to form spheroidal pellets were investigated for MCC/water pastes and some MCC/water/calcium carbonate pastes using the interrupted technique reported by Lau et al. (2014). A new quantitative parameter, named ‘dumb-bellity’, was developed to monitor the formation and disappearance of ‘dumb-bell’ shaped pellets in the early stages of the rounding process. Tests using mixtures of coloured extrudates confirmed that attachment of small fragments (‘fines’) to the waist of pellets was not responsible for the transition from dumb-bell to more spheroidal shapes. The results confirmed the findings of Lau et al., that rounding was the rate-limiting step. Extrudates prepared with up to 20 wt.% calcium carbonate, (the carbonate representing a hard, active pharmaceutical ingredient), were subject to the same Spheronisation mechanism. The time to spheronise the carbonate-containing pastes was longer, which could be related to the increased deformation resistance of these materials.
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The evolution of pellet size and shape during Spheronisation of an extruded microcrystalline cellulose paste
Chemical Engineering Research and Design, 2014Co-Authors: Cls Lau, S L Rough, David I. Wilson, Vincent Y. Lister, M ZhangAbstract:Abstract The process by which cylindrical rods of soft solid paste extrudate are converted into round pellets on a spheroniser (Marumeriser™) plate was studied by interrupting Spheronisation tests and measuring the size and shape of the pellets. Batches of 20 identical rods (20 mm long, 3 mm diameter) generated by ram extrusion of 47 wt% microcrystalline cellulose/water paste were spheronised at rotational speeds, ω, between 1200 rpm and 1800 rpm on a laboratory spheroniser. The time to complete Spheronisation was found to scale with ω−3.6, which was close to the ω−3dependency predicted by a simple collision model. Breakage occupied the first 10% of the process duration: rounding off was the rate-determining step. The evolution of pellet shape was classified into five stages, the duration of which was found to scale with Spheronisation time. Pellet shape, quantified by aspect ratio, circularity, shape and angularity factors presented by Sukumaran and Ashmawy (2001), showed similar behaviour for all ω studied. A phenomenological model is proposed which identifies different routes for small and large rod breakage products.
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a comparison of screen and ram extrusion Spheronisation of simple pharmaceutical pastes based on microcrystalline cellulose
International Journal of Pharmaceutics, 2013Co-Authors: D.i. Wilson, R Ward, C Seiler, S L RoughAbstract:Abstract The performance of two laboratory-scale extrusion apparatuses used to approximate the action of an industrial screen extruder, namely a multi-holed die ram extruder and a roller screen extruder, were compared. Both devices featured short dies (ram 2 mm, screen 1 mm) with die diameter 1 mm and hole area fraction approaching 0.25. A series of water/microcrystalline cellulose (MCC) pastes with water contents varying from 45 to 60 wt% were extruded and pellets obtained from subsequent Spheronisation of the extrudates characterised in terms of size and shape. Each device exhibited a different range of processing windows for acceptable spheronised products, with the ram apparatus being able to extrude a wider range of paste water contents than the screen device. The pellets obtained from extrusion–Spheronisation (E–S) of the pastes via the screen device were in general smaller, with a wider size distribution, than those from ram E–S. These results are attributed to the different mechanical histories experienced by the pastes in the two types of extruder, which lead to different extrudate densities being achieved. MCC/water/calcium carbonate pastes were also tested, where the latter component represented a ‘hard’ (non-deformable) active pharmaceutical ingredient. Addition of calcium carbonate increased the stiffness of the paste, which could be countered by adjusting the water content of the deformable MCC/water matrix within the extrudability limits of the latter material.
D.i. Wilson - One of the best experts on this subject based on the ideXlab platform.
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Experimental validation of a dimensional analysis of Spheronisation of cylindrical extrudates
Powder Technology, 2016Co-Authors: J Parkin, S L Rough, Ks Widjaja, Mp Bryan, D.i. WilsonAbstract:Abstract Extrusion–Spheronisation is a widely used technique for the manufacture of pellets with high sphericity and narrow size distribution. A dimensionless framework for describing the evolution of pellet shape with Spheronisation time is presented for the first time and is validated using new experimental data obtained with two families of materials: (i) microcrystalline cellulose (MCC)/water-based pastes with loadings of up to 15 wt% calcium carbonate, representing a ‘hard’ active pharmaceutical ingredient, and (ii) a lactose/MCC/water paste. The dimensional analysis of the pellet rounding stage identified the paste density and bulk yield strength, σ Y , as scaling quantities: σ Y was measured in separate extrusion tests and found to increase with increasing carbonate content. Higher paste strength gave longer Spheronisation times and less spherical pellets for a given set of Spheronisation conditions. The pellet aspect ratio was found to increase in a linear manner with the logarithm of Spheronisation time, progressing towards an asymptotic final value. This behaviour, which is evident in old data sets (e.g. Bryan et al. [1]) but has not been discussed previously, is compared with two simple models. High speed imaging was also used to examine the collision behaviour of pellets during the breakage and rounding stages in Spheronisation. This confirmed that the rounding phase was the rate-determining step. The velocities of a number of tracked pellets were consistently lower than the tip speed of the rotating friction plate, confirming previous findings in studies of beds of rotating pellets.
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Stages in Spheronisation: evolution of pellet size and shape during Spheronisation of microcrystalline cellulose-based paste extrudates
Powder Technology, 2015Co-Authors: Mp Bryan, S L Rough, Ln Atherton, S Duffield, D.i. WilsonAbstract:Abstract The stages of extrudate breakup and rounding to form spheroidal pellets were investigated for MCC/water pastes and some MCC/water/calcium carbonate pastes using the interrupted technique reported by Lau et al. (2014). A new quantitative parameter, named ‘dumb-bellity’, was developed to monitor the formation and disappearance of ‘dumb-bell’ shaped pellets in the early stages of the rounding process. Tests using mixtures of coloured extrudates confirmed that attachment of small fragments (‘fines’) to the waist of pellets was not responsible for the transition from dumb-bell to more spheroidal shapes. The results confirmed the findings of Lau et al., that rounding was the rate-limiting step. Extrudates prepared with up to 20 wt.% calcium carbonate, (the carbonate representing a hard, active pharmaceutical ingredient), were subject to the same Spheronisation mechanism. The time to spheronise the carbonate-containing pastes was longer, which could be related to the increased deformation resistance of these materials.
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a comparison of screen and ram extrusion Spheronisation of simple pharmaceutical pastes based on microcrystalline cellulose
International Journal of Pharmaceutics, 2013Co-Authors: D.i. Wilson, R Ward, C Seiler, S L RoughAbstract:Abstract The performance of two laboratory-scale extrusion apparatuses used to approximate the action of an industrial screen extruder, namely a multi-holed die ram extruder and a roller screen extruder, were compared. Both devices featured short dies (ram 2 mm, screen 1 mm) with die diameter 1 mm and hole area fraction approaching 0.25. A series of water/microcrystalline cellulose (MCC) pastes with water contents varying from 45 to 60 wt% were extruded and pellets obtained from subsequent Spheronisation of the extrudates characterised in terms of size and shape. Each device exhibited a different range of processing windows for acceptable spheronised products, with the ram apparatus being able to extrude a wider range of paste water contents than the screen device. The pellets obtained from extrusion–Spheronisation (E–S) of the pastes via the screen device were in general smaller, with a wider size distribution, than those from ram E–S. These results are attributed to the different mechanical histories experienced by the pastes in the two types of extruder, which lead to different extrudate densities being achieved. MCC/water/calcium carbonate pastes were also tested, where the latter component represented a ‘hard’ (non-deformable) active pharmaceutical ingredient. Addition of calcium carbonate increased the stiffness of the paste, which could be countered by adjusting the water content of the deformable MCC/water matrix within the extrudability limits of the latter material.
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A comparison of screen and ram extrusion–Spheronisation of simple pharmaceutical pastes based on microcrystalline cellulose
International Journal of Pharmaceutics, 2013Co-Authors: D.i. Wilson, R Ward, C Seiler, S L RoughAbstract:Abstract The performance of two laboratory-scale extrusion apparatuses used to approximate the action of an industrial screen extruder, namely a multi-holed die ram extruder and a roller screen extruder, were compared. Both devices featured short dies (ram 2 mm, screen 1 mm) with die diameter 1 mm and hole area fraction approaching 0.25. A series of water/microcrystalline cellulose (MCC) pastes with water contents varying from 45 to 60 wt% were extruded and pellets obtained from subsequent Spheronisation of the extrudates characterised in terms of size and shape. Each device exhibited a different range of processing windows for acceptable spheronised products, with the ram apparatus being able to extrude a wider range of paste water contents than the screen device. The pellets obtained from extrusion–Spheronisation (E–S) of the pastes via the screen device were in general smaller, with a wider size distribution, than those from ram E–S. These results are attributed to the different mechanical histories experienced by the pastes in the two types of extruder, which lead to different extrudate densities being achieved. MCC/water/calcium carbonate pastes were also tested, where the latter component represented a ‘hard’ (non-deformable) active pharmaceutical ingredient. Addition of calcium carbonate increased the stiffness of the paste, which could be countered by adjusting the water content of the deformable MCC/water matrix within the extrudability limits of the latter material.
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A novel lab-scale screen extruder for studying extrusion-Spheronisation.
International journal of pharmaceutics, 2013Co-Authors: M Zhang, R Ward, C Seiler, S L Rough, S. Mascia, D.i. WilsonAbstract:A novel apparatus, the laboratory roller screen extruder (termed the LRS), was developed to replicate key aspects of the geometry and shear strain rates generated near the screen of industrial screen extruders. The configuration of the LRS is reported alongside a commissioning study employing a cohesive 45 wt% water/microcrystalline cellulose paste. The key operating parameters which controlled the extrudate mass flowrate, force on the screen and roller torque were (i) the size of the gap between the top of the roller blade and the screen, and (ii) the roller rotational speed. The data suggest that the apparent shear rate, based on the blade-screen clearance, provides a quantitative criterion for scale-up. The amount of screen flex showed good agreement with a simple bending deformation model. Spheronisation of the extrudates gave pellets with a narrow size distribution and acceptable sphericity which would be acceptable for capsule filling. Optimisation of the pellet shape was not performed. The results indicate that the LRS can be used to assess formulations for industrial screen extrusion-Spheronisation.
