A Feasibility Study on Pellet Coating Using a High-Speed Quasi-continuous Coater

Pellet coating is traditionally carried out using the Wurster coater. This study investigated the feasibility of pellet coating in a newly developed coater built with a unique airflow system, the Supercell™ coater (GEA Pharma Systems, UK). A full factorial design study was carried out to evaluate the influences of the spray rate of the coating dispersion, batch size of the pellet load, pellet size fraction and plenum pressure of the fluidizing air on the color coating of pellets in the Supercell™ coater. Results showed that pellets could be successfully coated using the Supercell™ coater. Higher plenum pressures and lower spray rates were found to minimize pellet agglomeration during coating. Although coating efficiencies were comparable amongst the different pellet size fractions, larger batch sizes of pellets were coated with higher efficiencies. Process optimization was carried out for each pellet size fraction and a large batch size (120 g) in combination with a high plenum pressure (1,500 mm WC) were deemed optimal. Optimal spray rates differed according to pellet size fraction and a lower spray rate was required for smaller pellets. Pellet flow patterns observed during coating were dependent on the pressure drop across the fluidized load. A ‘swirling’ pellet flow pattern was generally observed at coating conditions which led to optimal outcomes.KEY WORDS: fluid bed, fluidization, pellet coating, pellet flow patterns, pressure drop, process optimization, Supercell™ coater     

Optimization of the pelletization process in a fluid-bed rotor granulator using experimental design

This study examined the effect of rotor speed, amount of water sprayed, and atomizing air pressure on the geometric mean diameter and geometric standard deviation of pellets produced in a fluid-bed rotor granulator using a 2³ factorial design and an optimization technique. Pellets were prepared by wet granulation. Equal amounts of microcrystalline cellulose, α-lactose monohydrate, and distilled water were used as the granulation liquid. The size and the size distribution of the pellets were determined by sieve analysis. The size of the pellets was found to be dependent on the amount of water added, while an increase in rotor speed decreased their size. Both factors were found to be statistically significant (P<.05). The effect of atomizing air pressure on pellet size was not statistically significant. None of the 3 factors significantly affected the geometric standard deviation of the pellets. The rotor speed and the amount of water sprayed were further selected in order to construct a mathematical model that correlates these factors with the geometric mean diameter of the pellets. For this purpose, the optimization technique 3² was used. The derived equation described the relationship between the the experimental design techniques applied were found to be suitable in optimizing the pelletization process carried out in a fluid-bed rotor granulator.     

Impacts of pellets injected from the low-field side on plasma in ITER

Impacts of pellets injected from the low-field side (LFS) on plasma in ITER are investigated using the 1.5D BALDUR integrated predictive modeling code. In these simulations, the pellet ablation is described using the neutral gas shielding (NGS) model. The pellet ablation model is coupled with the plasma core transport model, which is a combination of the MMM95 anomalous transport model and NCLASS neoclassical transport model. The boundary conditions are assumed to be at the top of the pedestal, in which the pedestal parameters are predicted using a pedestal model based on the theoretical-based pedestal width scaling (either magnetic and flow shear stabilization width scaling, or flow shear stabilization width scaling, or normalized poloidal pressure width scaling) and the infinite-n ballooning mode pressure gradient limit. These pedestal models depend sensitively on the density at the top of the pedestal, which can be strongly influenced by the injection of pellets. The combination of the MMM95 and NCLASS models, together with the pedestal and NGS models, is used to simulate the time evolution of the plasma current, ion and electron temperatures, and density profiles for ITER standard type-I ELMy H-mode discharges during the injection of LFS pellets. It is found that the injection of pellets results in a complicated plasma scenario, especially in the outer region of the plasma and the plasma conditions at the boundary in which the pellet has an impact on increasing the plasma edge density, but reducing the plasma edge temperature. The LFS pellet has a stronger impact on the edge as compared to the center. For fusion performance, the pellet can result in either enhancement or degradation, depending sensitively on the pellet parameters; such as the pellet size, pellet velocity, and pellet frequency. For example, when a series of deuterium pellets with a size of 0.5 cm, velocity of 1 km/s, and frequency of 2 Hz are injected into the ITER plasma from the LFS, the plasma performance, evaluated in terms of Q _fusion, can increase to 72% of that before the use of pellets. It is also found that the injection of pellets results in an increase in the ion and electron densities, but does not enhance the central plasma density. On the other hand, it results in the formation of another peak of the plasma density in the outer region near the plasma edge. The formation of the density peak results in the reduction of plasma transports near the edge by decreasing the contributions of ion-temperature-gradient and trapped electron modes, as well as kinetic ballooning modes.     

A Statistical Approach to Optimize the Spray Drying of Starch Particles: Application to Dry Powder Coating

This article describes the preparation of starch particles, by spray drying, for possible application to a dry powder coating process. Dry powder coating consists of spraying a fine powder and a plasticizer on particles. The efficiency of the coating is linked to the powder morphological and dimensional characteristics. Different experimental parameters of the spray-drying process were analyzed, including type of solvent, starch concentration, rate of polymer feeding, pressure of the atomizing air, drying air flow, and temperature of drying air. An optimization and screening of the experimental parameters by a design of the experiment (DOE) approach have been done. Finally, the produced spray-dried starch particles were conveniently tested in a dry coating process, in comparison to the commercial initial starch. The obtained results, in terms of coating efficiency, demonstrated that the spray-dried particles led to a sharp increase of coating efficiency value.     

Computer modeling of fluid dynamics related to a myocardial bridge in a coronary artery

Fluid mechanics associated with blood flows induced by the so-called myocardial bridge (MB) has been studied systematically using a computational fluid dynamic modeling of the Newtonian, incompressible, two-dimensional, unsteady flow in a channel with a time-dependently flushing in/out indentation. During each cycle, a train of vortex wave flow was observed downstream of the phasic stenosis and both upper and lower walls suffer severely from consistently high, oscillating wall shear stresses (WSS). Extensive studies were conducted on the influence of the Reynolds number, the geometry and the Strouhal number of the MB movement on the nature of the vortex flow and the time-dependent wall shear stress distribution. Special attention was drawn to the relationship between the vortex wave and the pressure distribution. It was found that the pressure gradient changed markedly during one cycle, which was apparently dominated by the dynamics of the indentation. A steep, adverse pressure gradient was observed when the indentation was flushing out, which corresponded to the existence of the most developing vortices. It implies the possibility that the MB in a coronary artery can produce an extremely low pressure region immediately downstream of the phasic stenosis, where elastic choking or collapse of the coronary artery might occur.     

PAT-Based Control of Fluid Bed Coating Process Using NIR Spectroscopy to Monitor the Cellulose Coating on Pharmaceutical Pellets

Current endeavor was aimed towards monitoring percent weight build-up during functional coating process on drug-layered pellets. Near-infrared (NIR) spectroscopy is an emerging process analytical technology (PAT) tool which was employed here within quality by design (QbD) framework. Samples were withdrawn after spraying every 15-Kg cellulosic coating material during Wurster coating process of drug-loaded pellets. NIR spectra of these samples were acquired using cup spinner assembly of Thermoscientific Antaris II, followed by multivariate analysis using partial least squares (PLS) calibration model. PLS model was built by selecting various absorption regions of NIR spectra for Ethyl cellulose, drug and correlating the absorption values with actual percent weight build up determined by HPLC. The spectral regions of 8971.04 to 8250.77 cm^?1, 7515.24 to 7108.33 cm^?1, and 5257.00 to 5098.87 cm^?1 were found to be specific to cellulose, where as the spectral region of 6004.45 to 5844.14 cm^?1was found to be specific to drug. The final model gave superb correlation co-efficient value of 0.9994 for calibration and 0.9984 for validation with low root mean square of error (RMSE) values of 0.147 for calibration and 0.371 for validation using 6 factors. The developed correlation between the NIR spectra and cellulose content is useful in precise at-line prediction of functional coat value and can be used for monitoring the Wurster coating process.     

Abrasion of suspended biofilm pellets in airlift reactors: importance of shape, structure, and particle concentrations

The detachment of biomass from suspended biofilm pellets in three-phase internal loop airlift reactors was investigated under nongrowth conditions and in the presence of bare carrier particles. In different sets of experiments, the concentrations of biofilm pellets and bare carrier particles were varied independently. Gas hold-up, bubble size, and general flow pattern were strongly influenced by changes in volume fractions of biofilm pellets and bare carrier particles. In spite of this, the rate of biomass detachment was found to be linear with both the concentration of biofilm pellets and the bare carrier concentration up to a solids hold-up of 30%. This implies that the detachment rate was dominated by collisions between biofilm pellets and bare carrier particles. These collisions caused an on-going abrasion of the biofilm pellets, leading to a reduction in pellet volume. Breakage of the biofilm pellets was negligible. The biofilm pellets were essentially ellipsoidal, which made three-dimensional size determination necessary. Calculating particle volumes from two-dimensional image analysis measurements and assuming a spherical shape led to serious errors. The abrasion rate was not equal on all sides of the biofilm pellets, resulting in an increasing flattening of the pellets. This flattening was oriented with the basalt carrier inside the biofilm and independent of the absolute abrasion rate. These observations suggest that the collisions causing abrasion are somehow oriented. The internal structure of the biofilms showed two layers, a cell-dense outer layer and an interior with a low biomass density. Taking this density gradient into account, the washout of detached biomass matched observed changes in volume of the biofilm pellets. No gradient in biofilm strength with biofilm depth was indicated. (c) 1997 John Wiley & Sons, Inc.     

Development of polysaccharide gel-coated pellets for oral administration: swelling and release behavior of calcium pectinate gel

The aim of this study was to examine the effect of pellet size, pectin type, pectin concentration, and dissolution medium on the swelling and drug release behavior of spherical pellets containing theophylline and coated with 2 different calcium pectinates, using a multi-level factorial design approach. The spherical pellets were prepared by an extrusion-spheronization method and then coated with calcium pectinate using the diffusion-controlled interfacial complexation technique, which provides a defect-free and uniform coating on solid cores. Theophylline release from the pellets was slowed by the application of the coatings. The time to release 50% of the payload (ie, T50) in an acidic medium was approximately 7 minutes from uncoated small pellets and was 55 minutes after an amidated calcium pectinate coat was applied; a comparable coat on large pellets showed a T50 of 93 minutes. Drug release profiles of dry coated pellets showed a lag time (all less than 20 minutes) when the gel coat hydrated and swelled, followed by a zero-order release. It was found that the release rate was controlled by the pellet size, pectin type, pectin concentration, and dissolution medium.     

Small-scale fluid motion mediates growth and nutrient uptake of Selenastrum capricornutum

1. A fluid‐flow reactor using submersible speakers was constructed to generate small‐scale fluid motion similar to conditions measured in open water environments; flow was quantified by particle image velocimetry. Additionally a Couette‐type rotating cylinder was used to generate shear flows; flow was quantified using an optical hotwire probe and torque measurements. Growth rates of the green alga Selenastrum capricornutum were determined from changes in cell counts and viability was tested using the fluorogenic probe fluoresceine diacetate. 2. Evidence that fluid motion directly affects growth rates was obtained as a significant difference between growth in a moving versus non‐moving fluid. A near 2‐fold increase in growth rate was achieved for an energy dissipation rate of ? = 10^?7 m² s^?3; a rate common in lakes and oceans. The onset of the viability equilibrium, identified as the day of the test period when the number of active cells equalled non‐active cells, was delayed by 2 days for moving fluid conditions as compared with a non‐moving fluid. 3. Nutrient uptake was determined by a decrease in the bulk fluid concentration and cellular phosphorus concentration was also estimated. The thickness of the diffusive sublayer surrounding a cell, a zone dominated by molecular diffusion, was estimated. Increasing fluid motion was found to decrease the thickness of this layer. The Sherwood number (ratio of total mass flux to molecular mass flux) showed that advective flux surrounding cells dominated molecular diffusion flux with regard to Péclet numbers (ratio of advective transport to molecular diffusion transport). Fluid motion facilitated uptake rates and resulted in increased growth rates, compared with no‐flow conditions. The rate‐of‐rotation and the rate‐of‐strain in a moving fluid equally mediated the diffusive sublayer thickness surrounding the cells. Our study demonstrates that small‐scale fluid motion mediates algal growth kinetics and therefore should be included in predictive models for algal blooms.     

Influence of vascular porosity on fluid flow and nutrient transport in loaded cortical bone

Load-induced fluid flow is a key factor in triggering bone modeling and remodeling processes that maintain bone mass and architecture. To provide an enhanced understanding of fluid flow in bone, unique computational models of a tibial section were developed. The purpose of the study was to examine the effects of incorporating vascular porosity on pore fluid pressure and resulting lacunocanalicular flow and to determine the role of load-induced fluid flow in tracer transport. Simulations revealed large local pressure gradients surrounding the vascular canals that were dependent on the magnitude and state (i.e., compressive or tensile) of the stress. Fluid velocity magnitudes were increased by over an order of magnitude in the dual-porosity model, relative to the single-porosity model. Fluid flow had a marked effect on tracer perfusion within the cortex. After 10 loading cycles, a 9-fold increase in tracer concentration, relative to diffusion alone, was observed in the compressive region where fluid exchange was greatest between the lacunocanalicular porosity and the vascular canals. Agreement was achieved between computational results and experimental investigations of electrokinetic phenomenon, tracer transport, cellular stimulation, and functional adaptation. The models produced substantial improvements in bone fluid flow simulation and underscored the significance of incorporating vascular porosity in models designed to quantify fluid pressure and flow characteristics within mechanically loaded cortical bone.     

Analysis of intra-uterine fluid motion induced by uterine contractions

Evaluation of the fluid flow pattern in a non-pregnant uterus is important for understanding embryo transport in the uterus. Fertilization occurs in the fallopian tube and the embryo (fertilized ovum) enters the uterine cavity within 3 days of ovulation. In the uterus, the embryo is conveyed by the uterine fluid for another 3 to 4 days to a successful implantation site at the upper part of the uterus. Fluid movements within the uterus may be induced by several mechanisms, but they seem to be dominated by myometrial contractions. Intra-uterine fluid transport in a sagittal cross-section of the uterus was simulated by a model of wall-induced fluid motion within a two-dimensional channel. The time-dependent fluid pattern was studied by employing the lubrication theory. A comprehensive analysis of peristaltic transport resulting from symmetric and asymmetric contractions is presented for various displacement waves on the channel walls. The results provide information on the flow field and possible trajectories by which an embryo may be transported before implantation at the uterine wall.     

Comparative chondrogenesis of human cells in a 3D integrated experimental–computational mechanobiology model

We present an integrated experimental–computational mechanobiology model of chondrogenesis. The response of human articular chondrocytes to culture medium perfusion, versus perfusion associated with cyclic pressurisation, versus non-perfused culture, was compared in a pellet culture model, and multiphysic computation was used to quantify oxygen transport and flow dynamics in the various culture conditions. At 2 weeks of culture, the measured cell metabolic activity and the matrix content in collagen type II and aggrecan were greatest in the perfused+pressurised pellets. The main effects of perfusion alone, relative to static controls, were to suppress collagen type I and GAG contents, which were greatest in the non-perfused pellets. All pellets showed a peripheral layer of proliferating cells, which was thickest in the perfused pellets, and most pellets showed internal gradients in cell density and matrix composition. In perfused pellets, the computed lowest oxygen concentration was 0.075 mM (7.5% tension), the maximal oxygen flux was 477.5 nmol/m²/s and the maximal fluid shear stress, acting on the pellet surface, was 1.8 mPa (0.018 dyn/cm²). In the non-perfused pellets, the lowest oxygen concentration was 0.003 mM (0.3% tension) and the maximal oxygen flux was 102.4 nmol/m²/s. A local correlation was observed, between the gradients in pellet properties obtained from histology, and the oxygen fields calculated with multiphysic simulation. Our results show up-regulation of hyaline matrix protein production by human chondrocytes in response to perfusion associated with cyclic pressurisation. These results could be favourably exploited in tissue engineering applications.     

Perfusion cultures and modelling of oxygen uptake with three-dimensional chondrocyte pellets

Chondrocyte pellets were cultivated in a perfused flow chamber and supplied with medium by a constant flow rate from a conditioning vessel. In this conditioning vessel the medium was aerated and used medium was exchanged semi-continuously. The higher amount of DNA and glycosaminoglycane (GAG) in these pellets compared to control cultures under stationary conditions showed a positive effect of the reactor system, compared to standard culture conditions. A diffusion reaction model was applied to calculate the oxygen uptake of the cell pellet and to describe the oxygen profile within the pellet. The model included diffusion within the cell pellet and oxygen uptake of the cells. Calculated data were compared to experimental data obtained by tissue engineered chondrocyte cell pellets. Model calculations agreed rather well with experimental data.     

Investigations of oxygen transfer into Penicillium chrysogenum pellets by microprobe measurements

A microcoaxial needle sensor with a tip diameter of ca. 0.7 mum was used as a microprobe to measure profiles of dissolved oxygen tension (DOT) within fixed pellets of Penicillium chrysogenum as a function of the DOT level around the pellet, in the presence and absence of bulk convective flow and turbulence. The investigations indicate that the oxygen transfer mechanism is complex. The results were interpreted by assuming the penetration convective flow into the entire pellet and penetration of turbulence into the outer range. A model was developed which was able to describe the measured DOT profiles very well. The model takes into account molecular and turbulent diffusion as well as convective flow as transfer mechanisms inside of the pellet. Structures of pellets used for microprobe measurements were evaluated by histological investigations. Considerable variations of mycelial density with radius within the pellets were found.     

Simulations of plasma behavior during pellet injection in ITER

Plasma behavior during pellet injection in ITER is investigated using a 1.5D BALDUR integrated predictive modeling code. In these simulations, the pellet ablation is described using the neutral gas shielding (NGS) model developed by Parks and Turnbull [Phys. Fluids 21, 1735 (1978)]. The NGS pellet ablation model that includes the ?B drift effect is coupled with a plasma core transport model, which is a combination of an MMM95 anomalous transport model and an NCLASS neoclassical transport model. The combination of core transport models, together with pellet model, is used to simulate the time evolution of plasma current, ion and electron temperatures, and density profiles for ITER standard type-I ELMy H-mode discharges during the pellet injection. It is found that the injection of pellet can result in either enhancement or degradation of plasma performance. The ?B drift effect on the pellet deposition is very strong in ITER. The plasma density with high field side pellets, which favorable with the ?B drift effect, is much higher and pellet can penetrate much deeper than that with low field side pellets.     

Effects of polymer additives on fermentation parameters in a culture of A. niger

Of 24 different polymer and surfactant materials examined, a carboxypolymethylene (“Carbopol”) was found to cause enhancement of respiration rates in an Aspergillus niger culture by as much as 200%. Enhancement of other fermentation parameters, such as cellular growth and amylase production, was also observed. The enhancement effects of Carbopol were examined with clusters of spores and mold pellets. In the first case, it appears that the ionized carboxyl groups of Carbopol induced electrostatic repulsion among the spores thus initiating pulp growth with increased interfacial area of contact between the mold and the nutrient medium. In the second case, the Carbopol additive formed a thin film attached to the surface of the pellets which seemed to be responsible for an increased rate of potassium transport and, hence, fermentation yields. Additive utilization as substrate and physiological changes in the culture were not observed in these cases. It was also found that the probability of pellet formation, the size of pellets formed, and the number of spores per pellet can be correlated to the energy input to the fermentation system.     

Statistical modeling of protein spray drying at the lab scale

The objective of this study was to examine the effects of formulation and process variables on particle size and other characteristics of a spray-dried model protein, bovine serum albumin (BSA), using a partial factorial design for experiments. Formulation variables tested include concentration and zinc:protein complexation ratio. Process variables explored were inlet temperature, liquid feed rate, drying air flow rate, and atomizing nitrogen pressure on a lab-scale spray dryer. Statistical data analysis was used to determine F ratios for each of the inputs, which provided a means of ranking the importance of variables relative to one another for each powder characteristic of interest. It was found that protein concentration and atomizing nitrogen pressure had the greatest effects on the particle size of the protein powder. For determining product yield, results showed that protein concentration was the critical variable. Finally, the outlet temperature was mostly influenced by inlet temperature and liquid feed rate. Mathematical models based on these input-output relationships were constructed; these models provide insight into some of the controllable variables of the spray-drying process. Published: March 20, 2002     

Steady-state pleural fluid flow and pressure and the effects of lung buoyancy

Both theoretical and experimental studies of pleural fluid dynamics and lung buoyancy during steady-state, apneic conditions are presented. The theory shows that steady-state, top-to-bottom pleural-liquid flow creates a pressure distribution that opposes lung buoyancy. These two forces may balance, permitting dynamic lung floating, but when they do not, pleural-pleural contact is required. The animal experiments examine pleural-liquid pressure distributions in response to simulated reduced gravity, achieved by lung inflation with perfluorocarbon liquid as compared to air. The resulting decrease in lung buoyancy modifies the force balance in the pleural fluid, which is reflected in its vertical pressure gradient. The data and model show that the decrease in buoyancy with perfluorocarbon inflation causes the vertical pressure gradient to approach hydrostatic. In the microgravity analogue, the pleural pressures would be toward a more uniform distribution, consistent with ventilation studies during space flight. The pleural liquid turnover predicted by the model is computed and found to be comparable to experimental values from the literature. The model provides the flow field, which can be used to develop a full transport theory for molecular and cellular constituents that are found in pleural fluid.     

The disappearance of muntjac (Muntiacus reevesi) and roe deer (Capreolus capreolus) pellet groups in a pine forest of lowland England

Reliable knowledge of the disappearance rate of faecal pellets is essential for converting pellet density to deer density when using standing-crop pellet-group counts. Disappearance of muntjac and roe deer pellet groups was monitored in four growth stages of a pine forest of lowland England over a 15-month period. Time to disappearance of the pellet groups (days) of both species significantly differed between habitats and months; it was shorter in late summer to early autumn and in habitats with more ground vegetation. Muntjac pellet groups disappeared more quickly than roe deer pellet groups. Time to disappearance of roe deer pellet groups was negatively correlated with air and grass temperature in pre-thicket and pre-fell habitats, while time to disappearance of muntjac pellet groups was negatively correlated with frequency of rainfall and positively correlated with the run of wind (air passage over a site within a 24-h period measured in km) in pre-thicket habitats. It is the time of the standing-crop pellet-group counts and the disappearance rate of pellet groups deposited in different months and habitats that determine the appropriate method for conversion of pellet-group density to deer density.     

Influence of operational variables on properties of piroxicam pellets prepared by extrusion-spheronization: A technical note

Summary and Conclusion  The processing conditions has a pronounced effect on the pellet properties. Drying conditions influenced the mean size and the drug release of the pellets. Because of the shrinking of the pellets upon drying at higher temperatures, the pellets also showed increased densities. Freeze drying almost prevented shrinking and thus led to the highest drug release. With an increase in the temperature of drying, the drug release rate decreased. Both spheronization time and spheronization speed affected the shapes of pellets, and the changes in shapes then affected the pellet flow properties. Within the studied range, the circularity of the pellets was affected more by the spheronization time than by the spheronization speed. Drying conditions influenced pellet friability, which decreased with an increase in drying temperature, indicating the formation of more dense structures at higher temperatures. The same result was obtained with spheronization time. With an increase in spheronization time, the friability decreased, because of the formation of more compact masses at higher spheronization time. Mean size was not affected by spheronization time or spheronization speed. Published: March 9, 2007