Paddle Wheel Speed Research Articles

Assessment of blend uniformity in a stream sampler device using Raman spectroscopy

This study describes the first implementation of Raman spectrometer in a stream sampler for the in-line monitoring of low drug concentration in poor flowability powder blends. Raman spectra were continuously acquired as the powder blends flowed through the stream sampler operating with a paddle wheel speed of 10 RPM and used to develop the calibration models. A calibration model was developed to quantify caffeine concentration from 1.50 to 4.50% w/w using Partial Least Squares Regression (PLS-R). Three test set blends were used to assess the prediction errors of the calibration model. Caffeine concentration was predicted for the test set blends with a root mean square error of prediction of 0.21% w/w and a low bias of −0.03% w/w. The calibration model showed good prediction performance with an estimated sample mass of 83 mg. Variographic analysis demonstrated the low process variance of the real-time spectral acquisition through minimum practical error and sill values. The results showed the ability of the Raman spectrometer coupled with the stream sampler to monitor low drug concentration for poor flowability blends.

In-line monitoring of low drug concentration of flowing powders in a new sampler device.

A novel sampler device for flowing powders was tested to quantify drug concentrations as low as 0.76% w/w in pharmaceutical powder blends. The sampler device was developed based on the powder flow behavior within a tablet press feed frame, following the principles laid down in the Theory of Sampling. Two Near-Infrared (NIR) spectroscopic calibration models were developed with powder blends that varied from 0.52 to 2.52% w/w and 1.51-4.52% w/w. The calibration models were able to determine caffeine concentration in test set blends with root mean square error of predictions and bias below 0.1% w/w. Samples were collected from the sampler device and analyzed by ultraviolet-visible (UV-Vis) to determine the caffeine concentration. A high agreement between the in-line NIR predictions and the sampled UV-Vis results was found. The paddle wheel speed in the sampler can be varied up to ±10% without affecting NIR predictions; however, the models did not respond adequately to a 25% increase in this speed. Variographic analysis showed that the sampler device may quantify low drug concentrations with nugget effects below 0.0050 (%w/w)2. This study demonstrate that the sampler device may handle throughputs up to 45kg/h, without significantly affecting the physical properties of powder blends.

A DEM approach to assess the influence of the paddle wheel shape on force feeding during pharmaceutical tableting

Pharmaceutical tablet quality is tightly controlled to ensure the patient’s safety. Though the tableting process is a well-known and accepted approach, process understanding is frequently built upon long-time experience of the operators. This is also true for the first step in tableting, the die filling where the powder is fed from the hopper through a force feeding system into the rotating dies of the turret. The current study considers a three-chambered force feeder of a FETTE 1200i, with the focus to evaluate the influence of the paddle wheel shape, which may either be of cylindrical or cuboid shaped blades, on tablet quality. A numerical approach utilizing the discrete element method allowed to compute the powder transfer in the tablet press which helps in identifying the optimal paddle wheel shape configuration. For instance, at a low turret – high paddle wheel speed, the cylindrical configuration revealed highest quality with respect to tablet mass, tablet mass variation, and content uniformity. In contrast, the cuboid configuration indicated better quality at a high turret – low paddle wheel speed. In addition, the detailed analysis of macroscopic and microscopic powder flow phenomena within the force feeder was performed which improves general process understanding in pharmaceutical development.

Development of an In-Line Near-Infrared Method for Blend Content Uniformity Assessment in a Tablet Feed Frame.

Process analytical technology (PAT) has shown great potential for in-line tableting process monitoring. The study focuses on the development and validation of an in-line near-infrared (NIR) spectroscopic method for the determination of content uniformity of blends in a tablet feed frame. An in-line NIR method was developed after careful evaluation of the impact of potential experimental factors on the robustness and model accuracy and precision. The NIR method was validated according to the principles outlined in International Conference on Harmonization-Q2 for validation of analytical procedures and was demonstrated to be suitable for monitoring blend content for the formulation under evaluation. Reliable measurements of blend homogeneity rely on representative sampling. To reach the appropriate scale of scrutiny for a unit dose, the study assessed factors that influence the effective sample size measured by NIR. Spectral averaging, integration time, and feed frame paddle wheel speed were found to influence the effective sample size measured by the NIR probe. The effective sampling size was also estimated by comparing the distribution of predicted values with the reference values. The development of a robust, in-line PAT method was facilitated by thorough understanding of the sensitivity of PAT sensors to factors affecting pharmaceutical processes and products.

Inline monitoring of the powder filling level within a rotary tablet press feed frame

The filling level within feed frames and the uniformity of the powder supply by feed frames for die filling have not been monitored so far during tableting processes. This study was intended to investigate if the powder filling level inside a rotary tablet press feed frame is affected by the feed frames' paddle wheel speed and/or by the turret speed. Furthermore, it was examined whether the filling level affects the resulting tablet masses while filling the respective dies. Two tableting excipients one with poor flowability and one with excellent flowability were selected as model powders.For inline analysis within the feed frame, a laser triangulator was used, which at a particular position scans the powder surface level within the filling chamber of the feed frame and, combined with the recognition of the angle position of the paddle wheel by a rotary encoder, calculates the filling level and the uniformity of the powder supply by an in-house written software.Results show that the turret speed, the paddle wheel speed and the powder characteristics may all affect the filling level within the filling chamber. The presented method is suitable for inline monitoring of the filling level in the filling chamber of the feed frame and the homogeneity of the powder supply for die filling during tableting. Moreover, a decrease of the filling level during tableting and/or a sudden refill effect of the filling chamber can be detected as well, which may occur under certain process settings at the end of the tablet production and may influence the tablet mass. The results also showed that initial deviations of the filling levels of the individual paddle wheel interspaces persisted until the end of the tableting runs, which might be one of the reasons for tablet mass deviations during production.

Two-Phase Flow Modeling of Solid Dissolution in Liquid for Nutrient Mixing Improvement in Algal Raceway Ponds

Achieving optimal nutrient concentrations is essential to increasing the biomass productivity of algal raceway ponds. Nutrient mixing or distribution in raceway ponds is significantly affected by hydrodynamic and geometric properties. The nutrient mixing in algal raceway ponds under the influence of hydrodynamic and geometric properties of ponds is yet to be explored. Such a study is required to ensure optimal nutrient concentrations in algal raceway ponds. A novel computational fluid dynamics (CFD) model based on the Euler–Euler numerical scheme was developed to investigate nutrient mixing in raceway ponds under the effects of hydrodynamic and geometric properties. Nutrient mixing was investigated by estimating the dissolution of nutrients in raceway pond water. Experimental and CFD results were compared and verified using solid–liquid mass transfer coefficient and nutrient concentrations. Solid–liquid mass transfer coefficient, solid holdup, and nutrient concentrations in algal pond were estimated with the effects of pond aspect ratios, water depths, paddle wheel speeds, and particle sizes of nutrients. From the results, it was found that the proposed CFD model effectively simulated nutrient mixing in raceway ponds. Nutrient mixing increased in narrow and shallow raceway ponds due to effective solid–liquid mass transfer. High paddle wheel speeds increased the dissolution rate of nutrients in raceway ponds.

In line monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using Near Infrared spectroscopy

Near infrared (NIR) spectroscopy was used to determine the drug concentration in 3% (w/w) acetaminophen blends within the complex flow regime of the tablet press feed frame just before tablet compaction. NIR spectra also provided valuable information on the powder flow behavior within the feed frame and were used to track when a process enters or leaves the steady state. A partial least squares regression calibration model was developed with powder mixtures that varied from 1.5 to 4.5% (w/w) by obtaining 135 spectra after steady state for each concentration while the feed frame and die disc operated at 30.5 revolutions per minute (rpm). The calibration model determined drug concentration in validation blends with a root mean square error of prediction and bias below 0.1% (w/w). The robustness of the NIR calibration model was evaluated by determining the effect of variation on the operating conditions (paddle wheel speed and die disc speed) on NIR predictions. This work found that the paddle wheel speed can be increased up to 30% and the die disc speed decrease 10% without affecting NIR predictions. The results demonstrated that paddle wheel speed has a significant effect on the wave powder behavior (frequency and amplitude) but does not have significant effect on the mass hold-up within feed frame. The die disc speed does not affect wave powder behavior but affects significantly the mass hold-up inside the feed frame. This information can be used to reduce the tablet weight variability and ensure that this critical attribute is met.

Design and analysis of flow velocity distribution inside a raceway pond using computational fluid dynamics.

Open raceway ponds are widely adopted for cultivating microalgae on a large scale. Working depth of the raceway pond is the major component to be analysed for increasing the volume to surface area ratio. The working depth is limited up to 5-15cm in conventional ponds but in this analysis working depth of raceway pond is considered as 25cm. In this work, positioning of the paddle wheel is analysed and corresponding Vertical Mixing Index are calculated using CFD. Flow pattern along the length of the raceway pond, at three different paddle wheel speeds are analysed for L/W ratio of 6, 8 and 10, respectively. Effect of clearance (C) between rotor blade tip and bottom surface is also analysed by taking four clearance conditions i.e. C=2, 5, 10 and 15. Moving reference frame method of Fluent is used for the modeling of six blade paddle wheel and realizable k-ε model is used for capturing turbulence characteristics. Overall objective of this work is to analyse the required geometry for maintaining a minimum flow velocity to avoid settling of algae corresponding to 25cm working depth. Geometry given in [13] is designed using ANSYS Design modular and CFD results are generated using ANSYS FLUENT for the purpose of validation. Good agreement of results is observed between CFD and experimental Particle image velocimetry results with the deviation of 7.23%.

Decrease in light/dark cycle of microalgal cells with computational fluid dynamics simulation to improve microalgal growth in a raceway pond

In this study, computational fluid dynamics (CFD) was used to systemically analyze the movement of algae in a vortex flow field produced by up-down chute baffles. The average cell light/dark (L/D) cycle period, vertical fluid velocity, fraction of time the algae was resides in light zone and the L/D cycle period were investigated under different paddlewheel speeds and microalgal concentrations. Results showed that the L/D cycle period decreased but the vertical fluid velocity increased when the up-down chute baffles were used. The L/D cycle period decreased by 24% (from 5.1s to 3.9s), and vertical fluid velocity increased by 75% when up-down chute baffles were used with paddlewheel speed of 30r/min. The probability of L/D cycle period of 3s increased by 52% from 0.29 to 0.44 with the up-down chute baffles. This led to approximately 22% increase in biomass yield without changing the paddlewheel speed.

Microdynamic analysis of particle flow in a confined space using DEM: The feed frame case

The effect of feed frame and paddle wheel design and operating conditions on particle flow is not fully understood. Performance optimization of the tablet press feed frames is an issue of great significance in the pharmaceutical industry. Inadequate die filling and the amount of shear-strain applied in the tablet compressing stage can result in losses of the finished product because of poor quality. Most feed frames have two or more compartments, which complicate the powder flow dynamics. Therefore, a feed frame was built based on a single paddle wheel to have a better understanding of the particle flow and the force exerted over the particles using discrete element method simulations. A factorial design was developed, which involves the paddle wheel speed, the number of paddles and the paddle height. Results showed that the faster the paddle wheel speed, the lower the relative standard deviation of the die weight. The number of paddles was also demonstrated to be an important factor on decreasing the die weight variability and affects the force exerted over the particles. These findings can lead to changes in feed frame design to avoid high die weight variability, reducing the undesired attrition and segregation effect improving tablet quality.

Improving CO2 fixation with microalgae by bubble breakage in raceway ponds with up–down chute baffles

The aeration gas was broken into smaller bubbles with enhanced local solution velocity to improve CO2 fixation with microalgae in raceway ponds with up–down chute baffles. A high-speed photography system and online precise pH probes were used to measure bubble generation and residence times, which were affected by paddlewheel speed, aerator orifice diameter, gas flow rate, and solution depth. Bubble generation time (from gas reaching aerator orifice surface to completely escaping from the aerator) decreased because of the enhanced local solution velocity, whereas bubble residence time increased because of the vortex flow field produced by up–down chute baffles. Bubble generation time decreased by 27% and bubble residence time increased by 27% when paddlewheel speed was 10r/min with an aeration gas rate of 0.03vvm. The decreased generation time and increased residence time of aeration bubbles promoted microalgae biomass yield by 29% in optimized flow fields in raceway ponds.

Enhanced flashing light effect with up-down chute baffles to improve microalgal growth in a raceway pond

Novel up-down chute baffles that sequentially generate clockwise and anticlockwise liquid vortexes were developed to increase vertical liquid velocity between the bottom dark area and the top light area in a raceway pond. The vertical liquid velocity, mixing time, and mass transfer coefficient were measured as functions of paddlewheel speed and air aeration rate by using a particle imaging velocimeter, pH probes, and dissolved oxygen probes. The up-down chute baffles decreased the liquid mixing time and increased the mass transfer coefficient by 41% and 25%, respectively. Besides, the vertical liquid velocity increased from ∼0.5cm/s to ∼6.1cm/s. As a result, the dark–light cycle period was reduced to 1/12. This enhanced flashing light effect with up-down chute baffles increased biomass yield by 32.6% in the same raceway pond.

Relationship between residence time distribution and forces applied by paddles on powder attrition during the die filling process

Abstract The die filling process, which happens prior to the compaction step, affects directly the quality of the final product (tablets). As paddles pass through the powder bed inside the feed frame, shear is applied to particles. Therefore, it is important to establish a relationship between residence time distribution (RTD) and forces applied by the feed frame paddles on powder attrition and overlubrication during the die filling process. The pulse injection method was used to study the RTD. The discrete element method (DEM) was also used to measure the RTD of particles by size ranges and the mean residence time (MRT) inside the feed frame. The experimental and DEM simulation design of experiments included 2 paddle wheel speeds (24 and 72 rpm) and 2 die disk speeds (29 and 57 rpm). Experimental results show that higher paddle wheel speeds lead to lower mean residence time, narrower RTD profiles, and larger number of paddle passes. The simulations RTD profiles are similar to an ideal continuous stirred tank reactor (CSTR) profile with a sharp peak and a tail. Operating conditions, feed frame exit contributions, and outlet mass flow rate affect the MRT. The RTD analysis by particle size shows that particle size segregation occurs where the smaller particles are leaving the feed frame faster. The level of powder confinement inside the feed frames can have a significant effect on powder attrition. As particle size increases, the compressive and tangential force applied to it increases. The tangential force data show that the level of attrition is also affected by the paddle wheel speed. This study explains in detail different factors that can affect the residence time distribution and the force applied to particles that can ultimately cause particle breakage and powder overlubrication.

Simulation of powder flow in a lab-scale tablet press feed frame: Effects of design and operating parameters on measures of tablet quality

The feed frame of a pharmaceutical tablet press is an important process component critical in defining both the total tablet mass and the amount of the active pharmaceutical ingredient (API) within the tablets. In addition to these quantities, the mechanical agitation of the feeder can cause attrition or over-lubrication of the powder blend or granulation flowing through the device. In order to better understand these effects, the discrete element method is used to model powder flow in a single paddle wheel feed frame of a laboratory-scale tablet press with varying particle, process, and equipment parameters. Results show that widely varying particle flow patterns and residence time distributions are achieved for varying paddle wheel shape, rotation direction, and rotation speed. Faster paddle wheel speeds generally lead to more uniform tablet masses whereas slower paddle wheel speeds perform less work on the particles (a surrogate for attrition) and move the particles a smaller distance (a surrogate for the extent of lubrication) in the feed frame before they enter a die and are compressed into a tablet. Finally, the effects of paddle wheel design and powder cohesion are also described.

Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy

New analytical methods are needed to understand and optimize the processes by which tablets are produced. Fette 3090 tablet presses are commonly used in the pharmaceutical industry. A near-infrared (NIR) probe was installed into a Fette 3090 feed frame to understand and monitor the die filling process. The second objective was to analyze in detail the different factors that could affect the prediction of the developed NIR calibration models. Two monitoring positions for NIR spectrometers were evaluated; one at each side of the feed frame. A powder wave behavior caused by the paddle motion was observed inside the feed frame. The study also revealed that NIR spectra can help in the understanding of powder flow inside the feed frame. It was demonstrated that NIR spectra baselines can also be used to determine changes in mass inside the feed frame. The new NIR method showed that the paddle wheel speed has a significant impact in the powder dynamics inside the feed frame. The baselines of the NIR spectra depended on the mass hold-up inside the feed frame and paddle wheel speed. Studies using blends were performed to develop a NIR calibration model based on the feed frame system dynamics to determine acetaminophen drug concentration variability during the die filling process. The study found that variation in the distance from the powder to the probe due to paddle wheel speed has a significant effect on the NIR prediction. This study found that with NIR spectroscopy, blend uniformity can be assessed with high accuracy during the die filling process using the corresponding paddle wheel speed in-line calibration model. NIR was demonstrated to be a good development tool for the in-line monitoring of powder during the die filling process.

Particle size segregation promoted by powder flow in confined space: The die filling process case

Tablet compression has great significance in the pharmaceutical industry since most of the drugs are in the tablet dosage form. The tablet press feed frame is used to fill powder into the empty dies. Die filling is one of the key steps to control final properties of tablets. Using the Discrete Element Method (DEM), a standard feed frame taken from a Manesty Betapress was simulated which represents the tableting process without the compression stage. DEM was used to understand the micro-macro dynamics of the particles inside the feed frame. Segregation behavior of a single material with a particle size distribution was investigated using this method. The DEM simulation components included 2 paddle wheel speeds (24 and 72rpm) and 2 die disk speeds (29 and 57rpm). Results obtained have highlighted the effect of feed frames on the powder properties. The DEM results show size segregation inside the feed frame and during the die filling stage. Velocity profiles and particle vectors show that the percolation phenomenon is the most significant segregation mechanism. Paddle wheel speed was demonstrated to be the most important factor to control particle size segregation inside the feed frame.

Monitoring blend potency in a tablet press feed frame using near infrared spectroscopy

A near-infrared (NIR) probe was installed into the feed frame of a rotary tablet press to monitor API concentration as a function of time. A series of step change experimental trials were completed, where a placebo blend was initially charged into the feed frame, and an active blend was layered above. The compression process was initiated, and process parameters, such as mass throughput rate, and feed frame paddle wheel speed were systematically varied.For the range of mass throughput rates studied, excellent correlations were shown between the NIR signal and weight corrected tablet potency from stratified tablet samples. A similar correlation was demonstrated for higher feed frame paddle wheel speeds. However, for lower feed frame paddle wheel speeds, a bias was observed between weight corrected tablet potency and the NIR signal. This finding suggests that compression process parameters, such as paddle wheel rotational speed and NIR probe location, must be optimized for different tablet press geometries to ensure that the NIR process signal can be related to tablet potency.This emerging application of Process Analytical Technology (PAT) may be used to identify powder segregation events during discharge of powder from an intermediate bulk container (IBC) or as a development tool to further understand powder mixing dynamics occurring within the feed frame. This may also be used as a diagnostic tool for fault detection during tablet compression. Finally, this PAT application may also be integrated with the tablet press control system as a gating or reject device for sub or super-potent tablets or enable Real-Time-Release testing (RTRt) through the continuous monitoring of the potency and homogeneity of powder circulating within the feed frame.

Large-scale biodiesel production using microalgae biomass of Nannochloropsis

The aim of this study is to investigate the large-scale algae production using Nannochloropsis sp. in indoor open ponds. One of the key factors in open pond productivity is the uniformity of distribution of nutrients and CO2. Therefore, the effects of paddlewheel speeds (1.4, 2.1 and 2.8 rad s � 1 ) on the productivity were also evaluated. The culture system

A Novel Flex-Stretch-Flow Bioreactor for the Study of Engineered Heart Valve Tissue Mechanobiology

Tissue engineered heart valves (TEHV) have been observed to respond to mechanical conditioning in vitro by expression of activated myofibroblast phenotypes followed by improvements in tissue maturation. In separate studies, cyclic flexure, stretch, and flow (FSF) have been demonstrated to exhibit both independent and coupled stimulatory effects. Synthesis of these observations into a rational framework for TEHV mechanical conditioning has been limited, however, due to the functional complexity of tri-leaflet valves and the inherent differences of separate bioreactor systems. Toward quantifying the effects of individual mechanical stimuli similar to those that occur during normal valve function, a novel bioreactor was developed in which FSF mechanical stimuli can be applied to engineered heart valve tissues independently or in combination. The FSF bioreactor consists of two identically equipped chambers, each having the capacity to hold up to 12 rectangular tissue specimens (25 x 7.5 x 1 mm) via a novel "spiral-bound" technique. Specimens can be subjected to changes-in-curvature up to 50 mm(-1) and uniaxial tensile strains up to 75%. Steady laminar flow can be applied by a magnetically coupled paddlewheel system. Computational fluid dynamic (CFD) simulations were conducted and experimentally validated by particle image velocimetry (PIV). Tissue specimen wall shear stress profiles were predicted as a function of paddlewheel speed, culture medium viscosity, and the quasi-static state of specimen deformation (i.e., either undeformed or completely flexed). Velocity profiles predicted by 2D CFD simulations of the paddlewheel mechanism compared well with PIV measurements, and were used to determine boundary conditions in localized 3D simulations. For undeformed specimens, predicted inter-specimen variations in wall shear stress were on average +/-7%, with an average wall shear stress of 1.145 dyne/cm(2) predicted at a paddlewheel speed of 2000 rpm and standard culture conditions. In contrast, while the average wall shear stress predicted for specimens in the quasi-static flexed state was approximately 59% higher (1.821 dyne/cm(2)), flexed specimens exhibited a broad intra-specimen wall shear stress distribution between the convex and concave sides that correlated with specimen curvature, with peak wall shear stresses of approximately 10 dyne/cm(2). This result suggests that by utilizing simple flexed geometric configurations, the present system can also be used to study the effects of spatially varying shear stresses. We conclude that the present design provides a robust tool for the study of mechanical stimuli on in vitro engineered heart valve tissue formation.

Design Characteristics of Single Hub Paddle Wheel Aerator

Aeration experiments, based on dimensional analysis, were conducted in brick masonry tanks of dimensions 2.9×2.9×1.6 m3 and 5.9×2.9×1.6 m3 to study the design characteristics of a single hub paddle wheel aerator. A generalized equation has been developed to estimate the optimum volume of water to be aerated at a given paddle wheel diameter (d) and speed (N) . A simulation equation with E [nondimensional number characterizing standard aeration efficiency (SAE)] and P* (nondimensional number characterizing power input per unit volume) provided a correlation better than that with E and F (Froude number) and E and R (Reynolds number) only. A simplified generalized equation correlating E and P* was developed which can be used to predict aeration efficiency for P* ⩽6.56 . Similarly, a simulation equation with Ne [(power number)(nondimensional number charcterizing power consumption)] and P* provided a correlation better than that with Ne and F and Ne and R only. The optimum dynamic condition at which maximum SAE...