Double-cone Blender Research Articles

Formulation and evaluation of novel herbal antidiabetic nutraceutical powder dosage using edible plant components of Tripura, India

BackgroundNutritional deficiency diseases are common in India and other developing countries. Recently, herbal nutraceutical products have diminished diseases related to nutrition and improper diet. The current study aimed to develop a powdered herbal nutraceutical using certain native edible plant parts from Tripura, India, and to assess its antidiabetic activity.MethodsPlant parts were selected based on the ethnomedicinal information of healers. Nutraceutical powder was prepared by a simple mixing method using a double cone blender. Bulk density, tapped density, Hausner quotient, Carr’s compressibility index, flow rate, and angle of repose were determined to evaluate the nutraceutical powder. The proximate composition was determined by The Association of Official Analytical Collaboration (AOAC) methods. Essential minerals were determined using an atomic absorption spectrophotometer (AAS). Vitamins (vit-C, vit-B9, vit-A, and vit-E) were determined using HPLC. The anti-diabetic activity of the nutraceutical powder was evaluated by the Oral Glucose Tolerant (OGTT) test.ResultsAll selected plants provided significant ethnomedicinal information. All physical parameters of the nutraceutical powder significantly matched the standard values. The formulated nutraceutical powder had a good caloric value (369 kcal), and a good amount of minerals and vitamins were found. Formulated nutraceutical powder shows significant antidiabetic activity.ConclusionBased on the results, it was concluded that formulated nutraceutical powder may minimize various malnutritional diseases and control the blood glucose label.

The effect of rotation speed and particle size distribution variability on mixability: An avalanche rheological and multivariate image analytical approach.

The utility of modulating rotation speed in tumble mixing and its mechanistic interplay with particle size distribution (PSD) variability in excipients remain underexplored. They were investigated in this study. For the present purpose, PSD of a commercial grade lactose was modified to reflect commercially relevant variations; and mixed with microcrystalline cellulose and chlorpheniramine in a double-cone blender, at various rotation speeds. Model of mixing was constructed using avalanche rheological properties and was also rendered as quantifiable visual models using avalanche rheological visual metric (ARVM), to uncover mechanistic relationships. ARVM was derived through multivariate image analysis of avalanche flow. It was observed that increasing rotation speed reduced the number of rotations needed to achieve blend homogeneity by 30-33% for PSD variants with 16-20% fines, while increasing the number of rotations by 134% in PSD variants with less than 15% fines (p≈0.00). ARVM successfully modelled (root mean square error of external validation=2.46%) and revealed the mechanistic interplay. With increased proportion of fines, lactose exhibited quasi-parabolic motion with disaggregation of soft agglomerates and improved mixing. With decreased proportion of fines, lactose flowed as coherent wave-like masses with imperceptible dispersive tendency and increased dilation, which impeded mixing. In conclusion, this study contributes to process understanding and ideas for designing robust mixing operations. It showcases the usefulness of a quantitative visual approach, exemplified by the ARVM, to evaluate material variability and uncover its mechanistic impact on processing.

Fabrication of Motorized Low Speed Double Cone Blender

Blending in powder metallurgy process is an important stage which affects the performance of the composite prepared through the process. In the present study an attempt is made to fabricate a double cone blender for enhancement of mixing process during the preparation of composite through powder metallurgy process.

Towards reliable optimization of metal powder—Lubricant mixing for high die filling performance: Exploring a rheology based approach

A previously unreported approach to optimize the time of an industry scale mixing operation for best filling performance, while ensuring premix uniformity, is tested. Mixing a base metal powder with a lubricant facilitates compacting and ejecting of powder compacts. However, the quality of lubricant admixing directly influences premix flowability and, therefore, the die filling performance of the premix. Insufficient lubricant admixing leads to non-uniform lubricant distribution, while excessive mixing, − to segregation or flowability degradation.Approximately 1.5 metric tons of a powder mix based on FL 4405 and a lubricant containing lithium compounds are mixed in a double cone blender. The optimum mixing time is estimated using a set of powder rheology measurements. It is then validated through conventional premix flowability and uniformity tests including Hall flowrate and burn-off-based probing of lubricant distribution, respectively. A streamlined subset of the performed characterization steps for the optimization of other premix formulations is proposed.

Scale-Up Strategy in Quality by Design Approach for Pharmaceutical Blending Process with Discrete Element Method Simulation.

An approach combining quality by design (QbD) and the discrete element method (DEM) is proposed to establish an effective scale-up strategy for the blending process of an amlodipine formulation prepared by the direct compression method. Critical process parameters (CPPs) for intermediate critical quality attributes (IQAs) were identified using risk assessment (RA) in the QbD approach. A Box–Behnken design was applied to obtain the operating space for a laboratory-scale. A DEM model was developed by the input parameters for the amlodipine formulation; blending was simulated on a laboratory-scale V-blender (3 L) at optimal settings. The efficacy and reliability of the DEM model was validated through a comparison of simulation and experimental results. Change of operating space was evaluated using the validated DEM model when scaled-up to pilot-scale (10 L). Pilot-scale blending was simulated on a V-blender and double-cone blender at the optimal settings derived from the laboratory-scale operating space. Both pilot-scale simulation results suggest that blending time should be lower than the laboratory-scale optimized blending time to meet target values. These results confirm the change of operating space during the scale-up process. Therefore, this study suggests that a QbD-integrated DEM simulation can be a desirable approach for an effective scale-up strategy.

Near infrared spectroscopy for rapid and in-line detection of particle size distribution variability in lactose during mixing

Particle size distribution (PSD) variability in excipients may cause unacceptable prolongation of mixing time needed to achieve blend homogeneity. Therefore, it is vital to modulate mixing through real-time monitoring of PSD variability. Notwithstanding the criticality of PSD variability, real-time measurement of PSD during mixing is relatively unexplored; and this is the focus of the present study. The model excipient was commercial grade lactose with modified PSD that conformed to the manufacturer’s specifications. It was mixed with microcrystalline cellulose and chlorpheniramine in a double-cone blender. High and low dose blends were prepared and near infrared spectroscopy (NIRS) was used to collect spectral data, during mixing, for chemometric modelling of PSD. Four modelling approaches based on partial least squares regression (PLSR) were applied. The models were highly interpretable and rapidly measured PSD near the beginning of mixing (5th to 6th rotation), with accuracy (relative standard error of prediction <5.0%, r2 ≈ 1.00, slope ≈ 1.00). Therefore, NIR chemometric modelling is a viable strategy to detect variability in PSD of excipients during blending and could enable real-time control of mixing. Most significantly, this strategy is potentially transferable to the monitoring and controlling of batch and continuous processes, where PSD is either a source of process variability or a critical quality attribute.

Investigating the effect and mechanism of particle size distribution variability on mixing using avalanche testing and multivariate modelling

Particle size distribution (PSD) variability in excipients is widely thought to affect the mixing process and the achievement of blend homogeneity. Yet, few studies have addressed this issue by attempting to ascertain the relationship and elucidate its mechanism. To address this, the model material, lactose, was modified to reflect commercially relevant PSD variations and mixed with microcrystalline cellulose and chlorpheniramine in a double-cone blender. Multivariate modelling and avalanche testing were applied to elucidate the relationship and mechanism. PSD variability can cause significant change in mixing time, by 8 times and 3 times (p ≈ 0.00) for high and low dose drug formulations, respectively. Achievement of blend homogeneity depended on the dispersive mixing mechanism (r2 = 0.99). Dispersive mixing was adversely affected by powder cohesiveness and powder dilation, which increased as the proportion of fine particles in lactose powder increased. This study yielded three conclusions. Firstly, PSD variability in pharmaceutical grade excipients can cause unacceptable prolongation in mixing time. Secondly, the impact of PSD variability on continuous mixing and other batch mixing of various scales, requires investigation. Lastly, the current findings can contribute to the development of robust mixing operations in the form of offline pre-emptive measures and inline process control strategies.

Establishment of blending control for Hand operated Double Cone Blender

In the current study, a fundamental approach is used to establish operation procedure, for a hand operated double cone blender. Initially, assuming for a potent drug, where in, the strength of the drug is very less in the final dosage form, a one percent concentration of potassium permanganate with respect to final one kilogram of blended powder using starch as diluent was planned. With a kind of geometric progression method, at a rate of 10 rotations per minute, the final outcome of the uniform distribution of the potassium permanganate was found to be for at least for fourteen hours of rotations, leading to concentration range of potassium permanganate 0.08 ± 0.025 mg per mg of final blended powder.

Discrete element method simulations and experiments of dry catalyst impregnation for spherical and cylindrical particles in a double cone blender

The dry impregnation of catalyst supports is a widely used process in the preparation of heterogeneous catalysts, however there has not been a lot of work done computationally on this process. In this work, discrete element method (DEM) simulations coupled with an algorithm for the transfer of fluid to and between particles are used to study dry impregnation. We use a previously developed model, which has been further validated with geometrically equivalent experiments and the results show very good agreement. The effects of rotational speed, particle size and particle morphology are explored in order to achieve the best overall mixing and fluid content uniformity in the particle bed. We study spheres and cylinders of different sizes and aspect ratios. Axial mixing analysis and liquid distributions are used to investigate the propagation of the fluid throughout the particle bed with the goal of understanding the effect of operational and material parameters and ultimately to improve fluid content uniformity in systems with particles of different morphologies. The fluid content uniformity is characterized by the relative standard deviation (RSD) of the liquid content from all the particles in the system. Our results show that cylinders always take less time to mix than spheres of the same diameter and mixing times are also shorter for cylinders of higher aspect ratios when compared to cylinders of smaller aspect ratio. Likewise, the times to reach good fluid content uniformity are shorter for cylinders with higher aspect ratios as compared with cylinders with lower aspect ratios. We also observe that mixing time in the axial direction for both spheres and cylinders followed an exponential function of the surface area to volume ratio. We found a linear correlation between the times to achieve good axial mixing and the times to achieve good fluid content uniformity in the entire particle bed, which suggests that mixing in the axial direction controls fluid uniformity in the entire particle bed.

Development of a Rational Design Space for Optimizing Mixing Conditions for Formation of Adhesive Mixtures for Dry-Powder Inhaler Formulations

The purpose of the present study was to develop guidance toward rational choice of blenders and processing conditions to make robust and high performing adhesive mixtures for dry-powder inhalers and to develop quantitative experimental approaches for optimizing the process. Mixing behavior of carrier (LH100) and AstraZeneca fine lactose in high-shear and low-shear double cone blenders was systematically investigated. Process variables impacting the mixing performance were evaluated for both blenders. The performance of the blenders with respect to the mixing time, press-on forces, static charging, and abrasion of carrier fines was monitored, and for some of the parameters, distinct differences could be detected. A comparison table is presented, which can be used as a guidance to enable rational choice of blender and process parameters based on the user requirements. Segregation of adhesive mixtures during hopper discharge was also investigated.

Dry catalyst impregnation in a double cone blender: A computational and experimental analysis

The dry impregnation of catalysts is widely used in industrial catalyst preparation, however, until recently, it has not been possible to model this system computationally. In this work, a novel algorithm for the spray and inter-particle transfer of fluid onto and within a rotating bed of granular catalyst support was explored using discrete element method (DEM). The simulations were validated by experiments utilizing a geometrically identical double cone blender fixed with a single nozzle impregnator. The effects of liquid flow rate and fill level were explored at a fixed rotation rate of 25rpm. Specifically, three flow rates of 1.5, 2.5 and 5L/h were selected and evaluated at a 30% and 45% fill fraction by volume. Mixing analysis and fluid concentration distributions were used both experimentally and computationally to investigate the propagation of fluid throughout the bed with the goal of modeling and improving industrial content uniformity. It was discovered that low flow rate systems and lower fill fractions resulted in better mixing and content uniformity throughout the bed. Results obtained from our model show good agreement with experiments, and therefore it was demonstrated that a novel fluid transfer algorithm incorporated into DEM could be used to accurately model dry catalyst impregnation, therefore introducing a new tool for optimizing catalyst manufacturing.

Comparing mixing performance of uniaxial and biaxial bin blenders

The dynamics involved in powder mixing remains a topic of interest for many researchers; however the theory still remains underdeveloped. Most of the mixers are still designed and scaled up on empirical basis. In many industries, including pharmaceutical, the majority of blending is performed using “tumbling mixers”. Tumbling mixers are hollow containers which are partially loaded with materials and rotated for some number of revolutions. Some common examples include horizontal drum mixers, v-blenders, double cone blenders and bin blenders. In all these mixers while homogenization in the direction of rotation is fast, mediated by a convective mixing process, mixing in the horizontal (axial) direction, driven by a dispersive process, is often much slower. In this paper, we experimentally investigate a new tumbling mixer that rotates with respect to two axes: a horizontal axis (tumbling motion), and a central symmetry axis (spinning motion). A detailed study is conducted on mixing performance of powders and the effect of critical fundamental parameters including blender geometry, speed, fill level, presence of baffles, loading pattern, and axis of rotation. In this work Acetaminophen is used as the active pharmaceutical ingredient and the formulation contains commonly used excipients such as Avicel and Lactose. The mixing efficiency is characterized by extracting samples after pre-determined number of revolutions, and analyzing them using Near Infrared Spectroscopy to determine compositional distribution. Results show the importance of process variables including the axis of rotation on homogeneity of powder blends.

Enhanced mixing in double cone blenders

Solubility behavior of d-mannitol (d-man) in pure water and four water-organic solvents from 288.15 K to 318.15 K at atmospheric pressure was studied by both phase equilibria and molecular modelling methods. A dynamic method was employed to determine the data on equilibrium, both molecular dynamic (MD) simulations and density functional theory (DFT) calculations were carried out to uncover the relationship between intermolecular interactions and solubility behavior. The MD results illustrate that the strength in hydrogen bond of solute-organic solvent captures the solubility ranking of d-man in corresponding mixed solvents, and the radial distribution function (RDF) plots indicate that organic solvents have enhancement effect on the water aggregation in solution which weakened the strong interaction between d-man and water molecules. Both of them suggest that solubility behavior not only depends on solute-solvent interaction, the solvent-solvent interaction also plays a key role in determining it. The solubility was further fitted by the modified Apelblat model, λh model, NRTL model and finally, mixing properties (enthalpy, Gibbs energy and entropy) were discussed, indicating the dissolution process is governed by both enthalpy and entropy of solution.

Granular segregation in the double-cone blender: Transitions and mechanisms

We investigate granular segregation in one of the most common industrial devices used in granular processing: the double-cone blender. We report several new and spontaneously occurring segregation patterns, including stripes, bands, and a symmetry-breaking state in which one species vacates half the tumbler. By varying the tumbling speed along with particle size and size ratio, we find that the transitions between segregated patterns are extremely sharp: Changes in fill level or speed of under one percent are sufficient to produce a reproducible qualitative change in the observed pattern. We show that the several distinct segregation patterns observed experimentally can be reproduced from a simplified model in which outward rolling on the convective granular cascade competes against inertial motion of rapidly moving large particles. Finally, we identify a cutoff particle size ratio above which large particles become buried in the cascading flow, and segregation appears to cease.

Enhanced mixing in double-cone blenders

Experiments were conducted comparing mixing performance in a conventional double-cone blender and in a double-cone blender that was modified by means of a stationary deflector plate in order to enhance axial particle flow. Mixing performance was assessed qualitatively using a transparent mixing vessel to visualize particle mixing patterns and determine the state of homogeneity at the mixture's surface during the entire experiment. Mixing performance was also examined quantitatively by repeatedly vacuuming several layers of beads, taking a digital image of the bed after vacuuming, and using image analysis to subdivide the images into samples and determine the composition of each sample. The effect of operating conditions (rotation rate, vessel fill percentage and total number of revolutions) was examined. Mixing was quantified in terms of the standard deviation of the concentration of a tracer. The evolution of the process was accurately described by a single-parameter model that characterized axial mixing as a first order process with a characteristic rate constant. For double-cone mixers of standard design, under all operating conditions, slow flow of particles through a vertical plane of symmetry at the center of the vessel caused poor mixing performance. Insertion of a deflector plate inclined relative to this plane was very effective in enhancing mixing. The effect of the deflector was to create a convective axial flow across the center of the mixer, increasing the mixing rate by a factor of 25:1.

Mixing dynamics in catalyst impregnation in double-cone blenders

The mixing of solids was studied in a 10 in. diameter acrylic scaled-down model of a commercial double-cone blender as a method of investigating catalyst impregnation variables. Layers of labeled and unlabeled particles were assembled in specific horizontal and vertical geometries and a Computed Tomography scanner was used to non-destructively image the particle bed in 10 mm slices at 50 mm intervals after different numbers of rotations through the mixing process. Experiments were performed with both 1/16 in. diameter pellets and nominally 100 μm diameter spherical particles in order to study the effect of particle to vessel diameter ratio. These studies showed that for both material sizes (1) axial mixing (perpendicular to the axis of rotation) was essentially complete within 10 to 20 rotations and that the surface was refreshed after a single rotation; (2) radial mixing (along the axis of rotation) was found to be significantly poorer; (3) filling the vessel 80% rather than 50% full resulted in segregation and therefore very poor mixing. All of these results were quantitatively confirmed in experiments in which vacuuming and image analysis were used to quantify the concentration of particles of a given color throughout the granular bed. These results suggest that, in coating operations—such as catalyst impregnation—the liquid spray distribution must reflect the volume distribution of the solid along the rotation axis in order to avoid uneven distribution of the liquid solution caused by slow axial mixing of the granular bed.

Studies on solids mixing in a double-cone blender

The mixing of free-flowing sand particles of larger size (−0.422+0.595 mm) with non-free-flowing salt particles of smaller size (−0.252+0.353 mm) has been studied in an experimental double-cone blender with no deflectors and with deflectors. In these studies the progress of mixing in the axial and radial directions has been followed separately. Four compositions with mixtures proportions of 20, 40, 60 and 80% sand by weight have been studied. It is observed that for the case with no deflectors complete mixing is rarely attained for compositions containing a greater proportion of free flowing sand particles. In such cases complete mixing can be attained having deflectors at suitable positions in the blender.