Showing papers on "High Shear Granulation published in 2011"
TL;DR: Extrusion forces recorded during processing of a mixture previously granulated in a high shear granulator were higher than when processed in a planetary mixture, which is probably the main cause of this phenomenon.
Abstract: A gravity feed extruder was adapted to monitor the extrusion forces, the temperature during processing and the rotational speed of the extruding cylinders. The extruder was used to evaluate the influence of particle size of insoluble material and of product solubility on the extrusion forces. Microcrystalline cellulose, dicalcium phosphate dihydrate and different lactoses were used as model compounds. Difference in lactose and microcrystalline cellulose particle size did not influence extrusion forces. The amount of water in the mixtures to be processed and the initial difference in solubility for some of the lactose types investigated influenced the extrusion forces dramatically. Extrusion forces recorded during processing of a mixture previously granulated in a high shear granulator were higher than when processed in a planetary mixture. Loss of water during high shear granulation is probably the main cause of this phenomenon.
46 citations
TL;DR: In this paper, the role of solid state surface chemistry on granulation performance of organic pharmaceutical solids was investigated by coagglomerating untreated and silanized d-mannitol powder from a narrow sieve fraction in a high shear process.
Abstract: This article presents a detailed study of the role of solid state surface chemistry on the high shear granulation performance of organic pharmaceutical solids. The sole effect of powder surface chemistry on granulation performance was investigated by coagglomerating untreated and silanized d-mannitol powder from a narrow sieve fraction in a high shear process. The wetting performance by polyvinylpyrrolidone (PVP) binder solutions was quantified using experimentally determined thermodynamic spreading coefficients, calculated from surface energy heterogeneity distributions obtained via inverse gas chromatography (IGC) measurements. Increases in binder wettability of the formulations correlated with increases in both granule size and compressive elastic moduli, which are attributed to an increase in interparticle contacts. In conclusion, starting materials surface chemistry plays a crucial role in final granule properties, even in highly agitated processes such as high shear granulation. The comprehensive ch...
36 citations
TL;DR: By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high- shear mixer.
Abstract: The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol−1 from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.
34 citations
TL;DR: In this article, the authors investigated the effect of granule formation, consolidation, and breakage and attrition on granule properties, and found that significant inhomogeneity existed in granule property, even for granules taken from the same batch at the same sampling time.
34 citations
TL;DR: In this article, the effects of fill volume on the properties of a high shear granulator were investigated. And the results showed that increasing the fill factor (batch size) increased the values of these material parameters.
33 citations
TL;DR: Three granulating binders in high drug-load acetaminophen blends were evaluated and a polymethacrylate binder enhanced tablet tensile strength with rapid disintegration in simulated gastric fluid, whereas polyvinylpyrrolidone and hydroxypropyl cellulose binders produced less desirable tablets.
Abstract: Three granulating binders in high drug-load acetaminophen blends were evaluated using high shear granulation and extrusion granulation. A polymethacrylate binder enhanced tablet tensile strength with rapid disintegration in simulated gastric fluid, whereas polyvinylpyrrolidone and hydroxypropyl cellulose binders produced less desirable tablets. Using the polymethacrylate binder, the extrusion granulation process was studied regarding the effects of granulating liquid, injection rate and screw speed on granule properties. A full factorial experimental design was conducted to allow the statistical analysis of interactions between extrusion process parameters. Response variables considered in the study included extruder power consumption (screw loading), granule bulk/tapped density, particle size distribution, tablet hardness, friability, disintegration time and dissolution.
25 citations
TL;DR: In this paper, the attributes of granola breakfast cereal produced by wet granulation are discussed and a case study employing granola production is presented, where the granulation process and operation conditions are discussed in detail.
Abstract: The present review discusses the attributes of granola breakfast cereal produced by wet granulation. Granola is an aggregated baked food product often eaten as a breakfast cereal containing natural ingredients such as oats, nuts and honey. Wet granulation is a unit operation where fine primary particulate materials (powders, grains etc.) agglomerate in the presence of a liquid binder to produce larger granules. High-shear granulation and fluidised bed granulation are the most common mode of wet granulation. Granulation prevents the segregation of co-agglomerated components, resulting in an improvement in content uniformity. In addition, the compression and dissolution characteristics, product attractiveness of the product are improved. The granulation process and operation conditions are discussed in detail and a case study employing granola production is presented.
18 citations
TL;DR: It was concluded that the largest fraction of optimal granules would be obtained at an impeller speed of 700 rpm with the chopper at 1,000 rpm allowing balances between flow establishment, segregation, and centrifugal forces.
Abstract: Chopper presence and then chopper speed was varied during wet high shear granulation of a placebo formulation using a PMA-1 granulator while also varying the impeller speed. The granules were extensively analyzed for differences due to the chopper. The effect of the chopper on the granules varied with impeller speed from no effect at a low impeller speed of 300 rpm to flow interruptions at an impeller speed of 700 rpm to minimal impact at very high impeller speeds as caking at the bowl perimeter obscured the effect of the chopper on the flow pattern. Differences in the granule flowability were minimal. However, it was concluded that the largest fraction of optimal granules would be obtained at an impeller speed of 700 rpm with the chopper at 1,000 rpm allowing balances between flow establishment, segregation, and centrifugal forces.
17 citations
TL;DR: In this article, a high shear mixer granulator was used to produce granola in a wet granulation process followed by oven drying, and the results enabled the optimal ranges of impeller speeds, liquid binder addition rate and the wet massing time to be established for this system, thereby aiding the manufacturing process in terms of controllability and reproducibility.
11 citations
TL;DR: Compaction behavior of melt granules were affected by their mean sizes, porosities, flow properties, binder, and moisture contents, and the last two factors were responsible for the disparities in compaction behavior.
Abstract: Recently, microwave-induced melt granulation was shown to be a promising alternative to conventional melt granulation with improved process monitoring capabilities. This study aimed to compare the physicochemical and compaction properties of granules produced from microwave-induced and conventional melt granulation. Powder admixtures comprising equivalent proportions by weight of lactose 200 M and anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350 under the influence of microwave-induced and conventional heating in a 10-L single pot high shear processor. The properties of the granules and compacts produced from the two processes were compared. Relative to conventional melt granulation, the rates at which the irradiated powders heated up in microwave-induced melt granulation were lower. Agglomerate growth proceeded at a slower rate, and this necessitated longer massing durations for growth induction. These factors prompted greater evaporative moisture losses from the melt granules. Additionally, nonuniform heating of the powders under the influence of microwaves led to increased inter-batch variations in the binder contents of resultant melt granules and a reliance of content homogeneity on massing duration. Agglomerate growth proceeded more rapidly under the influence of conventional heating due to the enhanced heating capabilities of the powders. Melt granules produced using the conventional method possessed higher moisture contents and improved content homogeneity. The compaction behavior of melt granules were affected by their mean sizes, porosities, flow properties, binder, and moisture contents. The last two factors were responsible for the disparities in compaction behavior of melt granules produced from microwave-induced and conventional melt granulation.
4 citations
Journal Article•
TL;DR: In this article, a comparative study of the granulation process focuses on the observation of granule size distribution (GSD) is performed with process kinetics, and the authors use a 1-D discretized population balance and Equi-Partition of Kinetic Energy (EKE) coalescence model.
Abstract: High-shear and fluid-bed processes were used for granulation of dolomite powder into agrochemical product. In this paper, comparative study of the granulation process focuses on the observation of granule size distribution (GSD). Considerable difference between high-shear and fluid-bed GSDs is analyzed with process kinetics. Simulation of dynamic development of GSD is achieved with application of a 1-D discretized population balance and Equi-Partition of Kinetic Energy (EKE) coalescence model. The used approach indicates for both processes (high-shear and fluid-bed granulation) the presence of coalescence growth as a dominant mechanism in the dolomite granulation process. Deviations between simulated and real GSDs signify the probable existence of other granulation mechanism(s). A posteriori approach by the integral method was used for coalescence rate constant estimation. The generated kinetic considerations represent a valuable step towards a comprehensive perspective of dolomite granulation and implementing the acquired knowledge in real-life agrochemical granulation.
TL;DR: The aim of this study was to investigate the correlation between the growth behaviour and in‐vitro dissolution rate of water‐insoluble drugs prepared with high‐shear wet granulation.
Abstract: Objectives The aim of this study was to investigate the correlation between the growth behaviour and in-vitro dissolution rate of water-insoluble drugs prepared with high-shear wet granulation.
Methods Granules containing nimodipine, microcrystalline cellulose, low-substituted hydroxypropylcellulose and aqueous solution of hydroxypropylcellulose were prepared and the effects of independent process variables, including impeller speed and liquid-to-solid ratio were taken into consideration. The mean granule size, granule-size distribution (GSD), porosity and surface properties were monitored at different kneading times to identify the granule-growth mechanisms simultaneously. A computer-based method was applied to simulate the dissolution behaviour of polydisperse granules based on the GSD data.
Key findings The in-vitro dissolution rate of drug was high for the early stages of granulation and sharply decreased when coalescence and consolidation of granules started, approaching a flat and low level when granules were sufficiently consolidated. The simulated dissolution results were in agreement with experimental observations and were significantly affected by the GSD, porosity and surface properties of granules during the granulation process. Moreover the GSD was directly related to the granule-growth behaviour and mechanisms.
Conclusions In general, it was concluded that the dissolution properties of nimodipine basically correlated with the growth behaviour of granules in a high-shear mixer. The simulation method based on GSD can be used as a convenient and rapid way to predict the dissolution properties for formulation development and granulation optimization.
20 Jan 2011
TL;DR: In this article, the role of primary particle properties and process parameters (e.g., composition, primary particle size distribution, mixing speed, liquid flow rate and amount) on the final granule characteristics were investigated.
Abstract: Among all the powder agglomeration processes, high shear wet granulation is one of the most commonly used techniques. It consists of the agglomeration of different powders through the addition of a granulating fluid and a vigorous mixing. Industries often turn to high shear granulation mainly to avoid segregation of critical components in a powder mixture, improve flowability and compactibility. Despite the great importance of this technique in many industrial activities, it is not totally clear how changes in the initial powder mixture or in process variables can affect the final product properties. Moreover, scale-up of high shear granulators is still difficult to perform.
The present research mainly focuses on the high shear wet granulation of pharmaceutical powders. Particularly, this research aims at closing the gap in understanding the role of primary particle properties (e.g. composition, primary particle size distribution) and process parameters (e.g. mixing speed, liquid flow rate and amount) on the final granule characteristics. Scale-up effects on the powder flow patterns were investigated as well.