General overview of equipment for granulation and coating processes Granulators and coaters using mainly convective heat and mass transfer and low agitation High shear granulators
Michael Jacob
Handbook of Powder Technology, Vol. 2, Chapter 9, Elsevier Science B.V.
2007
This chapter provides a short introduction into drying, granulation and coating equipment. Owing to the very wide field of applications and processes a huge number of equipment types have been developed. Because of this some examples of equipment basics were explained here in more detail and other types were mentioned only as an overview. In the developing phase of processes and also of products equipment suppliers should be contacted to select the right type and size of equipment and to optimize processes. Additional standard literature references contain information about other processing principles and types of equipments.
English version
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Characterization of the fluidization behaviour and studies for coating, granulation and agglomeration
Michael Jacob, Elka Piskova, Lothar Mörl, Gerhard Krüger, Stefan Heinrich, Mirko Peglow, Karl-Heinz Rümpler
Tagungsband Nr. O81-003, 1-13, Session: Particulate Systems-Formulation, Topic: Advancing the Fundamentals (7th World Congress of Chemical Engineering incorporating the 5th European Congress of Chemical Engineering Glasgow, Scotland, July 10-14, 2005)
2005
In this work the fluid dynamics and the process behaviour of different types of spouted beds for drying, coating and granulation of particles are investigated. So, experiments with an empty bed and many bulk materials under dry and wet conditions were carried out, whereby the apparatus- and bed pressure drop was measured in relation to Archimedes number, free cross-section areas of the gas entrance, air volume flow rate, bed mass and different entrance conditions. Equations for the minimal fluidization velocity were formulated and the time profiles of the gas oscillations were recorded by use of a pressure sensor and the corresponding measuring techniques.
Axel Schiffmann, Jochen A. Dressler, Bernhard Luy, Hans Leuenberger
Sonderdruck, pharmind 66, Nr. 8, 1024-1030, ECV - Editio Cantor Verlag, Germany
2004
Due to increasing demands for an automated cleanability of processing equipment, equipment manufacturers have improved their product design for an optimum performance of the Cleaning In Place (CIP) process with respect to GMP standards. In this context it is important to assess if and eventually how these design improvements do affect the properties of granules manufactured in this fluid-bed system. Besides other design variations especially the bottom plate and the product retention filters are considered as critical magnitudes of influence in a fluid-bed process. The conventional product retaining filter systems used for this study consist of a seamed polyester fabric with a mesh size of approximately 20 µm. During a process this type of cloth filter is cleaned by means of pneumatic shaking cylinders which generate a periodically up and down movement of the bag type filter unit for a specified time. The product recovery filters developed for a WIP/CIP process are cylindrical filter cartridges consisting of stainless steel material with a mesh size of 10 µm in this study. Instead of the up and down movement the novel cartridges are periodically purged with bursts of compressed air at a pressure of 6 bar. The study compares standard granule material obtained in a fluid-bed top spray granulator which was modified for a better cleanability during a WIP/CIP process with granules obtained in a conventionally designed unit. The granulations are carried out under equal process conditions with the same formulation. The goal of this study is to detect eventual differences between the granule properties. For the comparison of the quality of the granule properties the bulk and tapped density, loss on drying, angle of repose, particle size distribution and the uniformity of drug content were measured. Scanning Electron Micrographs were prepared to visualize possible morphological differences. Within this study it can be concluded that a top-spray granulation process optimized in a conventionally designed unit can be transferred to a WIP/CIP designed fluid-bed granulator without changing process variables. The investigated design improvements do not affect the granule quality.
Sonderdruck, Powder and Bulk Engineering, CSC Publishing Inc.
Continuous fluidized-bed processing is becoming increasingly popular for producing food, chemical, and pharmaceutical powders and granules. This article introduces you to two forms of fluidized-bed processing: allomeration and spray granulation. Sections detail these processes, describe equipment that provides them, and explain how each process can be controlled to achieve a final product with the desired properties.
Modelling and simulation tools
S. Heinrich, M. Peglow, M. Henneberg, J. Dressler, L. Mörl, M. Jacob
Proc. International Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Nürnberg, 15. - 18.03.2004
The fluidized bed spray granulation (FBSG) is a process used for the production of granular high-quality, free-flowing, low-dust and low-attrition solids originating from liquid products, e. g. solutions, suspensions, melts and emulsions. The advantage is the coupling of the wetting, drying, particle enlarging, shaping, homogenisation and separation processes and the production in a single processing step. Especially for large production units a continuous operation of the FBSG is desirable. The continuous granulation process presents, unlike to the batch-operation, the advantage to operate the plant under stationary condition at high throughputs. The stationary operation point is reached, provided constant granulate spectrum beside constant mass flows and constant thermal conditions, whereby initially fed granulates have to be removed at all. Sometimes this unsteady phase lasting up to a few hours. The aim of the following examinations is to study the stability behaviour of the fluidized bed. Depending on the seeds formation mechanisms – overspray (non-deposited dried drops), attrition, separation - a narrow or wide particle size distribution is obtained. In respect to the heat and mass transfer processes a simple ID model is coupled with population balances. For the calculation of the temperature and humidity distributions supplementary a 3D model is presented.
Anette Seo, Per Holm, Torben Schæfer
European Journal of Pharmaceutical Sciences 16 (2002) 95-1005, Elsevier Science B.V.
2002
This study was performed in order to evaluate the effects of binder droplet size and type of binder on the agglomerate growth mechanisms by melt agglomeration in a fluidised bed granulator. Lactose monohydrate was agglomerated with melted polyethylene glycol (PEG) 3000 or Gelucire 50/13 (esters of polyethylene glycol and glycerol), which was atomised at different nozzle air flow rates giving rise to median droplet sizes of 40, 60, and 80 µm. Different product temperatures were investigated, below the melting range, in the middle of the melting range, and above the melting range for each binder. The agglomerates were found to be formed by initial nucleation of lactose particles immersed in the melted binder droplets. Agglomerate growth occurred by coalescence between nuclei followed by coalescence between agglomerates. Complex effects of binder droplet size and type of binder were seen at low product temperatures. Low product temperatures resulted in smaller agglomerate sizes, because the agglomerate growth was counteracted by very high binder viscosity or solidification of the binder. At higher product temperatures, neither the binder droplet size nor the type of binder had a clear effect on the final agglomerate size.
Apparate, Verfahrensvarianten, Möglichkeiten zur Einflussnahme auf Produkteigenschaften
Produktgestaltung in der Partikeltechnologie, Fraunhofer Institut für Chemische Technologie (ITC), Pfinztal
Wirbelschichtapparate finden in vielen Bereichen der Wirtschaft breite Anwendung. Das Einsatzfeld umfasst dabei sowohl Wärme- und Stoffübertragungsprozesse, wie beispielsweise Kühlung, Trocknung und Kalzinierung, als auch komplexe Mehrphasenprozesse wie Agglomeration, Sprühgranulation und Coating. Im Rahmen dieses beitrages wird Schwerpunkt gelegt auf Prozesse, bei denen Flüssigkeiten in Wirbelschichten eingedüst werden. In der folgenden Übersicht sind die zu betrachtenden Prozesse und häufig erwünschte Produkteigenschaften zusammengefasst. Die folgenden Abschnitte stellen grundlegende Zusammenhänge dar, ohne den Anspruch auf Vollständigleit zu erheben. Es werden elementare Prozessmechanismen erläutert und Ideen zur Produkt- und Prozessgestaltung geweckt. Einige Beispiele sollen Anregungen zur Entwicklung neuartiger eigenschaftsorientierter Produkte geben.
German version
Robert Pišek, Odon Planinšek, Matjaž Tuš, Stane Srcic
Sonderdruck, pharmind 62, Nr. 4, 312-319, ECV - Editio Cantor Verlag, Germany
2000
The aim of this research work was to investigate the influence of disc surface and its speed on the direct pelletization logy is "single pot" method of pellet production based on fluid bed technology. Two series of experiments have been carried out on GPCG 1 (Glatt Powder Coater Granulator) fluid bed apparatus. In the first series of the experiments mixture of 350 g of pentoxifylline and 150 g microcrystalline cellulose were used for pellets production. In the second series of experiments, the same amount of ketoprofen was used instead of pentoxifylline. In both series suspension of EudragitR NE 30 D was used as liquid binder but in each series at different concentration. Within each series of experiments the process variables were kept constant within limitations of the process, except rotational speed of the disc during agglomeration and spheronization step. Additionally, two different rotating discs were used; one with smooth and the other with textured surface. The results show that both surface and rotational speed of the disc have influence on shape, surface and size of pellets while there is less effect on true density, humidity content and yield of the experiment. Keeping rotational speed of the smooth disc constant during agglomeration of powder particles and increasing rotational speed during spheronization of agglomerates results in more spherical pellets with larger diameters and smoother surfaces. The influence of rotating disc with textured surface is opposite to the previously mentioned influence of smooth disc. Increasing rotational speed during spheronization step at the constant speed during agglomeration step results in smaller and less spherical pellets with rougher surface.
Axel Schiffmann, Dr. Bernhard Luy, Dr. Markus Bättig, Prof. Dr. Hans Leuenberger
Sonderdruck, Pharma Technology Journal, Nr. 1080, Seite 206-223
In der pharmazeutischen Industrie verwendete Produktionsanlagen zur Herstellung fester Arzneiformen werden manuell oder vollautomatisch gereinigt. Um einen vollautomatisch ablaufenden Reinigungsprozess zu realisieren, der pharmazeutischen (resp.: GMP-) Anforderungen genügt, müssen viele Anlagenteile in Konstruktion und Design z. T. erheblich verändert werden. Ein wichtiger Aspekt ist hierbei das sog. Total Containment: CIP-Fähigkeit und Total Containment bedingen sich gegenseitig und müssen in gleichem Maße bei der Entwicklung berücksichtigt werden. Die Verwirklichung dieses vollkommen geschlossenen Produkt-Handlings ist eine notwendige Voraussetzung zur Realisierung dieses neuen Anlagentyps. Dieser Beitrag beschreibt am Beispiel einer Wirbelschichtanlage, wie durch Veränderungen der konventionellen Bauart und der Peripherie ein solches Ziel erreicht werden kann. Die in diesem Zusammenhang verwendeten Abkürzungen WIP/CIP werden klar voneinander abgegrenzt. WIP (washing in place) bezeichnet eine halb- oder vollautomatische Reinigung mit entweder undefiniertem Reinigungsresultat oder aber mit dem Ergebnis, dass die Anlage noch nicht im GMP-Sinne sauber ist. CIP (cleaning in place) dagegen bezeichnet den Gesamtprozess einer vollautomatischen Reinigung einschließlich aller Faktoren, die auf das Reinigungsergebnis Einfluss haben, einschließlich des Nachweises, dass das Akzeptanzkriterium der Reinigungsvalidierung erreicht wurde. Eine Vergleichsstudie zwischen der manuellen und vollautomatischen Reinigung zeigt, dass durch systematische Veränderung der einzelnen Anlagenteile in Verbindung mit einem vollautomatischen Reinigungsprogramm ein höherer Reinigungsgrad erreicht werden kann. Des Weiteren kann eine Aussage über die Reproduzierbarkeit des Reinigungserfolges getroffen werden.
In the pharmaceutical industry production equipments of the manufacture of solid dosage forms are cleaned manually, semi- or fully-automated. In order to implement a fully automated cleaning process which meets pharmaceutical (i.e. GMP-) requirements, many conventionally used components must be changed considerably with respect to construction and design. An important aspect is the so-called Total Containment: CIP-ability and Total Containment are interdependent and must be considered equally with the development. The realisation of the Total Containment is an absolute prerequisite for the implementation of this new type of equipment. By the example of a fluid bed system this article describes, how this can be achieved by modifications of conventional equipments and of peripheral devices. The abbreviations WIP/CIP used in this context are clearly defined. WIP (washing in place) means semi or fully automated cleaning with either undefined result of cleaning or with the result that the system is not yet clean according to GMP-requirements. CIP (cleaning in place), on the other hand, stands for the entire process of a fully-automated cleaning to a GMP-conform level, including all factors, which have influence on the cleaning result. This includes the proof that the acceptance criterion of the cleaning validation was achieved. A comparison study between the manual and fully-automated cleaning shows that by systematic modification of the individual components in connection with a fully-automated cleaning program a higher cleaning grade can be achieved. Furthermore, a statement about the reproducibility of cleaning success can be met.
Dr. Karlheinz Rümpler, Dr. Ulrich Walter
Sonderdruck, Food Technologie Magazin, Dr. Harnisch Verlag
Futtermittelzusätze werden häufig durch Fermentation gewonnen, liegen also zunächst in flüssiger Form vor. Traditionell werden in aufwendigen Verfahrensschritten Nebenprodukte abgetrennt. Die gereinigte Fermantationsbrühe wird dann zur Kristallisation gebracht und anschließend getrocknet. Die dabei entstehenden kristallinen Produkte sind bei der weiteren anspruchsvollen Verarbeitung in der Mischfutterindustrie aufgrund der schlechten Rieselfähigkeit und der hygroskopischen Eigenschaften nur schwer zu handhaben. Ziel unserer Entwicklungsarbeit war es, die gesamte Fermentationsbrühe mit allen Rückständen und Nebenprodukten zu trocknen und in ein rieselfähiges, staubfreies und lagerstabiles feinkörniges Produkt kleiner 1 mm zu überführen. Die Granulationstrocknung in der Wirbelschicht nach dem AGT-Verfahren ist für solche Aufgaben bestens geeignet. Mit ihr ist es möglich, Lösungen, Suspensionen und Schmelzen in feste Stoffe zu überführen. Entweder wird dabei die flüssige Phase verdampft und der Trockenstoff gewonnen oder bei Schmelzen durch Unterkühlung die Kristallisation erreicht.
Dr. Karlheinz Rümpler, Michael Jacob
1999
In vielen Bereichen der Wirtschaft erlangen granulierte sowie instantisierte Produkte immer größer werdende Bedeutung. Dabei liegen die Anwendungsschwerpunkte in den Produktgruppen Instantnahrungsmittel, Instantgetränke und Komponenten für die Lebensmittelindustrie. Bei der Herstellung derartiger Produkte erweisen sich kontinuierliche Wirbelschichtverfahren als sehr geeignet. Ihre Vorteile liegen in den sehr guten Stoff- und Wärmeübergangsbedingungen bei kompaktem Aufbau der Anlage. Mit der kontinuierlichen Wirbelschicht-Fließrinne steht eine Anlagentechnik zur Verfügung, die vielseitig einsetzbar ist und ohne grundlegende technische Veränderungen zur Herstellung verschiedener Produkte geeignet ist. Es sind Anlagengrößen vom Labormaßstab bis hin zur Massenproduktion realisierbar. Ein wesentlicher Vorteil liegt in der Flexibilität sowie Durchführbarkeit verschiedener Prozesse in einer Anlage, was die Zukunftssicherheit der Investition garantiert.
Sonderdruck, Marketing & Food Technology, Dr. Harnisch Verlag
1998
Many powder and granular products are coated to improve their properties, and the engineering involved in coating processes is subject to continuous development. In the pharmaceuticals industry, for example, various coatings are used not only to control the release of substances or to adjust the flavor, but also to improve stability or structure. Intermittent fluidized-bed coaters have proved effective in providing this kind of finish. Where large volumes are involved, however - as in the food industry - continuous coating has considerable advantages. A new continuous coating system has been developed for such applications that has the flexibility required for a large material throughput while providing the coating quality demanded in the food industry.
F. Norring Christensen, P. Bertelsen
Sonderdruck, Drug Development and Industrial Pharmacy, 23(5), 451-463, Marcel Dekker, Inc.
1997
The Wurster-based fluid-bed coating process is often treated as just another fluid-bed coating process. However, there are significant differences between the two types of fluid-bed coatings. The Wurster-based coating process does not contain any fluid-bed regions in the traditional sense, as it is a circulating fluid-bed process. Four different regions within the equipment can be identified: the upbed region, the expansion chamber, the downbed region, and the horizontal transport region. The size of these regions is determined by the dimensions of the coating apparatus. Part of the upbed region constitutes the coating zone where the spray mist hits the substrate (the material that is going to be coated). The coating process consists of three phases: the start-up phase, the coating phase, and the drying/cooling phase. During the coating phase, several processes take place simultaneously. They are: atomization of the film solution/suspension, transport of the film droplets to the substrate, adhesion of the droplets to the substrate, film formation, the coating cycle of the substrate, and the drying of the film. When discussing the coating process, it is important to consider properties of the substrate. Key properties of the substrate determine important process properties such as bed expansion, bubble properties, slug properties, and spouting. The most important properties of the substrate are the density of the particles, their diameter, and their stickiness. The process characteristics are very different in each of the four regions. The upbed region is the most difficult to control. It is here that the most sensitive processes in relation to the coating occur. The product flow in the upbed region is a dilute vertical pneumatic conveying. The pneumatic conveying is controlled by the upbed fluidization air rate. Slugging is a frequent problem with the flow in this region for dense and large substrates. The airflow is the combined airflows of the fluidization air and the nozzle air.
Gudrun Ding
Sonderdruck, ZFL 5+6/1994, Hüthig GmbH, Heidelberg
1994
Pulvrige Substanzen bereiten beim Dosieren, Abfüllen und Transportieren oftmals Probleme durch hohen Staubanteil und schlechte Rieselfähigkeit. Durch Agglomeration derartiger Substanzen wird das Handling wesentlich erleichtert. Darüber hinaus bilden sich durch die Anlagerung feiner Partikel poröse Granulate, die sich durch besonders schnelle Dispergierbarkeit auszeichnen. Für die Herstellung von Instantgranulaten werden in der Lebensmittelindustrie heute verschiedene Verfahren eingesetzt.
A. Gottschalk
Sonderdruck, powder handling & processing März/1993
1993
The following article is an introduction to unique thermo-mechanical continuous processing technology which transforms a liquid or a powder based feed stream into dust-free particulates. The key features of this technology are: a fluidized particle bed, an integrated particle classification system, and a continuous material feed and discharge.
Dr. Karlheinz Rümpler
Glatt-Sonderdruck
Veränderte Lebensgewohnheiten und steigende Qualitätsansprüche der Verbraucher führen zu einer stark wachsenden Nachfrage nach hochwertigen Convenience-Produkten. Der Markt stellt damit ständig neue Anforderungen an die Lebensmittelindustrie und ihre Herstellungsverfahren. Multifunktionelle Techniken wie das Trocknen, Granulieren und Coaten von Partikeln in der Wirbelschicht haben daher in den letzten Jahren zunehmend an Bedeutung gewonnen. Eine vorteilhafte Anwendung findet die Wirbelschichttechnologie beispielsweise beim Coaten von Inhalts- und Zusatzstoffen. Der Einsatz solcher mikroverkapselter Produkte bietet vielfältige anwendungstechnische Vorteile wie den Schutz vor Oxidation oder chemischen Reaktionen mit der umgebenden Matrix, verringerte Verluste beim Herstellungsprozess, kontrollierte Freisetzung von Wirkstoffen (z. B. Gewürze und Backhilfsmittel), deutlich verlängerte Mindesthaltbarkeit und höhere biologische Wertigkeit. In diesem Beitrag soll ein kurzer Überblick über Verfahren und Anwendungen dieser speziellen Technologie gegeben werden.
David M. Jones
Sonderdruck, Pharmaceutical Engineering, März 1991
1991
Fluidized bed processing has evolved from simply drying to granulating, pelletizing, and film coating. Water and organic solvents can be used; the latter presenting challenges in avoidance of both safety and emission problems. Vacuum fluidized processing combines the intrinsic safety of operating under vacuum with the high drying rates of fluidized beds. As a totally enclosed process, it has application with highly potent or toxic materials, as well as oxygen sensitive products.
Jozwiakowski, Franz, Jones
Sonderdruck, Pharmaceutical Reseach, Vol.7/No.11, Nov. 1990
1990
The equipment modifications and process changes necessary to perform hot-melt particle coating in a fluid bed granulator are reviewed. A specific case is presented in which partially hydrogenated cottonseed oil is coated onto fine granules (mean particle size, 77 µm; range 10-150 µm, one standard deviation is 10 µm) composed of a hydrophobic drug and sucrose. The major variables were product bed temperature, temperature of the wax, spray rate, and atom temperature pressure. The product bed temperature was selected to give the optimum congealing rate, and the latter three variables were varied in a statistically designed experiment. The physical properties of wax-coated granules fabricated using combinations of process variables were examined. Response surface analysis was used to determine the optimum process settings in terms of dissolution, particle size, and density of the coated product. This system proved quite adequate for the production of uniformly coated granules, with the best product being obtained at the optimized conditions using 120°C atomization air and molten coating temperature, 30 g/min as the spray rate, and an atomization air pressure of 5 bar.
Grundlagen und Erfahrungen bei der Anwendung eines neuen Wirbelschichtverfahrens
