Fluid bed granulators offer a wide range of possibilities for feeding of. Our multifunctional lab and pilot systems for high shear granulation have proven themselves many times in process development and in reliably transferring from a laboratory to a production scale. Population balance model development, validation, and. Growth of granules and densification of the powder. Recent progress in high shear wet granulation process. Realtime monitoring of granule properties during high.
High shear processing req uires a lower percentage of water addition to produce granules of a larger particle size. The present research mainly focuses on the high shear wet granulation of pharmaceutical powders. Control strategy for process development of highshear wet. For any two dynamically similar systems, all the dimensionless numbers necessary to describe the process have the same numerical value 96.
Modelbased analysis of high shear wet granulation from batch. The most obvious ones are that wet granulation can improve the flow properties of the input. As a service to our customers we are providing this early version of the manuscript. The water spray rate of the scaleup batches was increased as a. The pma system comprises of three machines, offering total flexibility in system design with capacities of 11800 l. Among all the powder agglomeration processes, high shear wet granulation is. The granulating module of a high shear wet granulator mainly consists of a mixing bowl, an impeller, and an auxiliary chopper, and some are equipped with process analysis devices e. Pdf wet granulation in laboratory scale high shear mixers. The high shear wet granulation process was scaled up to 1. It is applied in several technological processes in the chemical and pharmaceutical industries. At the same experiment points, granules at all scales had similar size distribution, surface morphology, and flow properties. Bladegranule bed stress in a cylindrical high shear granulator. High shear wet granulation, powder technology 2012, doi.
The clinical research process in the pharmaceutical industry. A pat approach to improve process understanding of high shear. May 15, 2020 granulation with a high shear granulator is thought to be simpler, because it involves fewer process parameters than granulation with a fluid bed dryer. The model is aligned to adequately describe the high shear mode of granulation operation in a batch process. Scaleup studies on high shear wet granulation process. A population balance modeling pbm framework has been employed for modeling purposes which is then utilized to obtain accurate predictions of the process. With so many variables involved in a granulation process, it is no wonder that more and. High shear wet granulation in tsg involves many different process and equipment variables. Typically, granulation involves agglomeration of fine particles into larger granules, typically of size range between 0. The tip velocity, or speed of the fluid at the outside edge of the rotor, will be higher than the velocity at the center of the rotor, and it is this difference in velocity that creates shear. Dec 09, 2020 the high shear mixer granulator is designed to optimize the wet granulation process. It was concluded that the effectiveness of high shear wet granulation could be improved by choosing a proper combination of starting material and process parameters and by monitoring the mass motion during the process. Sep 04, 2015 process steps does not require current facilities to be modified high shear mixer water added for granulation granulation dried to wet granulation fluid bed drying blending and compaction film coating packaging preheating. The optimal endpoint can be thought of as the factor affecting a number of agglomerate properties fig.
Dynamic similitude for wet granulation would imply that the wet mass flow patterns in the bowl are similar. Used to turn a finepowder heterogeneous mixture into a uniform granulation, with increased particle size and higher density, offering proper flow and compactness properties, in a short time process and with repeatability. High shear granulation is an effective way to turn. Pdf scaleup studies on high shear wet granulation process.
Wet granulation endpoint as a factor in tableting optimization agglomeration of particles in wet granulation have been studied extensively 24, 79. Jan 28, 20 high shear mixture granulation dry powder mixing approx 25 mins liquid binder addition approx 12 mins wet massing wet sieving of granules drying dry sieving of granules12720 satara college of pharmacy, satara. The pharmaceutical granulation process entails wet and dry granulation. Flow diagram of the telemetric impeller stress sensor system. The machine discharges the wet mass through a wet mill which is capable of breaking any agglomerate. The high shear wet granulation hswg process is a size enlargement process used to improve the powder properties of the formulation such as the bulk density and powder flowability for the subsequent processes and to impart desirable properties to it. Development of regime map for steady state high shear wet. Wet granulation involves low shear, high shear, and. Abstract high shear wet granulation is widely used in the pharmaceutical industry, however it is still difficult to predict the results of granulation and explain the relevant results. Pdf effect of high shear granulation process parameters.
Effect of operating conditions and physicochemical. Challenges in wet granulation understanding the effect of process settings on granulation performance process evolution product quality 4 mostly theoretical approaches tracking granule attributes. Pdf scaleup of a high shear wet granulation process using a. Granulation was then carried out in a continuous high shear mixer granulator, glatt gcg 70. In this paper, a continuous high shear wet granulation process was examined based on a placebo formulation comprising 70%. Optimum liquid requirement for granulation has been found to vary with. Mar 01, 2021 the granulating module of a high shear wet granulator mainly consists of a mixing bowl, an impeller, and an auxiliary chopper, and some are equipped with process analysis devices e. High shear mixer granulator wet granulation process. High shear wet granulation hswg is a unit operation in the manufacturing process that can significantly impact the quality of the final product and therefore, needs to be fully understood. Granulation is the process of forming grains or granules from a powdery or solid substance, producing a granular material. Rohit ramachandran the addition of binder to facilitate the granulation in high shear wet granulation hswg process can be achieved either by adding a binder liquid with uniform viscosity.
High shear wet granulation hswg is a shaping process for granulation that has been enhanced for application in the pharmaceutical industry. Effect of operating conditions and physico chemical. Fluid bed granulators offer a wide range of possibilities for feeding of raw materials and discharge of finished products. A pat approach to improve process understanding of high.
Wet granulation can be divided into three main processes of low shear, high shear. Two types of granulation technologies are employed. The effect of the physical states of binders on highshear wet. Effects of process and design parameters on granule size. Novel approach to evaluating granulation and segregation. A newly developed miniscale high shear granulator was used for scaleup study of wet granulation process from 0. Abstracthigh shear wet granulation is widely used in the pharmaceutical industry. It is expected that this information will be valuable for future manufacturing processes using both labscale and largescale high shear mixers.
Pdf scaleup of the high shear wet granulation hswg process is considered a challenge because hswg is complex and influenced by numerous factors. Handbook of pharmaceutical granulation technology, second edition. Wet granulation high shear mixer wettability growth kinetics friability porosity the wet granulation process is sensitive to changes in product properties and process variables. The high shear wet granulation hswg process is a size enlargement process used to improve the powder properties of the formulation such as the bulk density and powder owability for the subsequent processes and to impart desirable properties to it. Lab and pilot systems glatt integrated process solutions. Granulation, the process of particle enlargement by agglomeration techniques, is routinely used across several industries to transform the properties of compressible powder blends 1.
It is a key process adopted in a range of industries for 4 production of pharmaceuticals, detergents, agricultural and food products, agrochemicals, enzymes etc. Improved understanding of the high shear wet granulation. The wet granulation process is sensitive to changes in product properties and process variables. Impeller torque and motor power consumption for a small high shear mixer fielder. High shear granulation results in an improved flow of the resulting granules for improved weight control during compression of tablets. There are many reasons that a wet granulation process is employed. High shear granulation high shear wet granulation process. Mixer agglomeration and in particular high shear wet granulation is a unit operation typically used. Torque curves recorded during granulation are found to allow good control of the process. It also shows the setup of a professional high shear granulator, aka high shear mixer and i. However, study of hswg is complex and challenging due to the relatively poor understanding of hswg, especially for sticky powderlike herbal extracts.
Alternative method for producing organic fertiliser from. Investigation of high shear wet granulation processes. Pdf effect of high shear granulation process parameters on. A high shear mixer uses a rotating impeller or high speed rotor or both to create flow and shear. Under various operation conditions and granulation bowl sizes, powder mixture composed of anhydrous caffeine, dmannitol, dibasic calcium phosphate, pregelatinized starch and corn starch was granulated by adding water. High shear mixer granulator wet granulation process ste. Defining scaling criteria in high shear granulation. Improve flow property and compression characteristics. A pat approach to improve process understanding of high shear wet granulation through inline particle measurement using fbrm c35 jun huang, 1goldi kaul, julia utz,2 pedro hernandez, victor wong, daragh bradley,1 arwinder nagi,1 des ogrady3 1pharmaceutical development center, wyeth pharmaceuticals, 401 n middletown road, pearl river, new york 10965 2excella gmbh.
High shear wet granulation is a significant component procedure in the pharmaceutical. Scaleup studies on high shear wet granulation process from. Wet granulation has been and continues to be the most widely used agglomeration process. Wet granulation in laboratory scale high shear mixers. Pdf wet granulation in laboratory scale high shear. Pdf pharmaceutical granulation processes, mechanism and the. At 6% binder level, hardness values were essentially equivalent for all binder materials, although low shear granulation processes tended to. Particularly, this research aims at closing the gap in understanding the role of. Moreover, scaleup of high shear granulators is still difficult to perform. The aim was to investigate the effect of granulation parameters.
This binder can be added in molten form, but the high shear process offers the benefit of allowing the binder to be added in its solid state. Abstract the effect of binder properties on torque curves, granule growth kinetics, wet mass consistency and dry granule strength has been investigated in this study. Introduction to tableting by wet granulation dfe pharma. Realtime monitoring of granule properties during high shear. This work aimed to evaluate the commonly used scale. The wet granulation process has been impacted over the last 25 years by the development of improved equipment, innovative research, novel polymeric binders, and even process analytical. Pharma solutions methocel as a wet and dry granulation binder. This research examined a high shear wet granulation process and subsequent manufacturing of a tablet containing a biopharmaceutics classification system bcs class ii drug, gliclazide low. The design maximizes product processing and contained handling. Purpose increasing water addition appears to increase particle size for both high shear and rotor processing.
High shear granulation or rapid mixture granulation process for immediate release ir formulation know how for the impeller and chopper speed scaleup rule for wet granulation process is most important for pharmaceutical technology transfer team and formulation research and development team. For high dose drugs, poor flow and compaction of the active mean that wet. In this study, we used salvia miltiorrhiza granules to investigate the hswg process. It is an important guide if you want to become a professional in fluid bed granulation process. It is the ultimate in versatility, with modular options for blending, high shear granulating and melt or wet pelletizing. This animation illustrates the process of high shear granulation. In wet granulation process a granulating liquid is used to facilitate the agglomeration process. For high viscosity binders higher wet mass consistencies but lower dry granule strengths have been observed. Pdf closing the gap in series scale up of high shear wet. Wet granulation edit in wet granulation, granules are formed by the addition of a granulation liquid onto a powder bed which is under the influence of an impeller in a high shear granulator, screws in a twin screw granulator 1 or air in a. Granulation runs have been performed on a fine cohesive microcrystalline cellulose powder avicel 105, d 50 20. High shear granulators often produce a wet mass after the completion of the granulation process. A high shear mixer received 19 may 2011 granulator was used to produce granola in a wet granulation process followed by oven received in revised form drying.
High shear mixer granulation using food grade binders with different. Experimental materials all the chemicals used in this research were of standard pharmaceutical grade. Modelbased analysis of high shear wet granulation from. Investigation of high shear wet granulation processes using. Improved understanding of the high shear wet granulation process. In addition, the use of the pregelatinized starch in the formulation also led to a reduction in the wall adhesion of the material. By granulating api with other excipients, it is possible to obtain different physical properties for the granulated sample, e. Among all the powder agglomeration processes, high shear wet granulation hswg, which is a typical batch process, is one of the most commonly used techniques. This article presents a new process analytical technology pat approach to monitor batch evolution process trajectory with regard to in process particle characterization during granulation. Granulation process transforms fine powders into freeflowing, dust free granules that are easy.
Or to test various processing options in wet granulation. Granule properties such as particle size, porosity, flow, and tabletability, and tablet dissolution were compared across scales using scale. Calculation of impeller and chopper speed during rmg wet. The optimal process and formulation are based on the knowledge of the granule growth mechanisms and of the effects of product properties and process variables. Remember, this is the main subject of this article. To keep the froude number constant, the impeller speed was set at 597 rpm for the pma1, and 435 rpm for the pma65. In a melt granulation process, the binder solution of a standard wet granulation process is replaced with a meltable binder. It is another example of a wet granulation process. The high shear wet granulation process using highshear granulator can be divided into 5 stages and they included.
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