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At least 73 records · Page 4Linked to original sources

PubMed2001

Melt agglomeration with polyethylene glycol beads at a low impeller speed in a high shear mixer.

This study was performed in order to evaluate the possibility of obtaining spherical agglomerates with a high content of meltable binder by a melt agglomeration process in a high shear mixer. Lactose monohydrate was melt agglomerated with polyethylene glycol (PEG) 1500 or 6000 in a 10-l high shear mixer at an impeller speed of 400 rpm. The PEG 1500 was used as a size fraction of beads, and the PEG 6000 as a fine powder, a powder, unfractionated beads, and size fractions of beads. It was found to be possible to incorporate a high amount of PEG (28% m/m of the amount of lactose), because the rather low impeller speed applied in the present experiments caused less densification of the agglomerates. The fine powder of the PEG 6000 caused a complete adhesion of the mass to the bowl shortly after melting. A rapid agglomerate growth by coalescence was found to be the dominant growth mechanism when agglomeration was performed with the PEG 6000 powder. The PEG beads resulted in a slow and more controllable agglomerate growth, because the growth occurred primarily by an immersion of the lactose particles in the surface of the molten binder droplets. The initial shape of the agglomerates produced with the PEG beads was similar to the spherical shape of the beads. This shape could not be maintained during the process due to a breakage of the agglomerates caused by a hollow structure of the PEG beads.

Microspheres↗

PubMed2004

A novel in-plane passive microfluidic mixer with modified Tesla structures.

An innovative in-plane passive micromixer using modified Tesla structures, which are used as passive valves, has been designed, simulated, fabricated and successfully characterized in this paper. Simulation and experimental results of the developed novel micromixer have shown excellent mixing performance over a wide range of flow conditions in the micro scale. The micromixer realized in this work has achieved even better mixing performance at a higher flow rate, and its pressure drop is less than 10 KPa at the flow rate of 100 microl min(-1). This micromixer shows characteristics similar to Taylor dispersion, with contributions from both diffusion and convection. The mixer has a diffusion domain region at low flow rate, but it moves to a convection domain region at high flow rate. Due to the simple in-plane structure of the novel micromixer explored in this work, the mixer can be easily realized and integrated with on-chip microfluidic devices and micro total analysis systems (micro-TAS).

Journal Article↗

PubMed2004

An optimised split-and-recombine micro-mixer with uniform chaotic mixing.

A second generation micro-mixer, being a further optimised version of a first prototype, relying on the consequent utilisation of the split-and-recombine principle is presented. We show that the mixing can be characterized by a positive finite-time Lyapunov exponent although being highly regular and uniform. Using computational fluid dynamics (CFD) we investigate the mixing performance for Reynolds numbers in the range of about 1 to about 100. In particular for low Reynolds numbers (Re < 15) the CFD results predict an almost ideal multi-lamination. Thus, the developed mixer is especially suited for efficient mixing of highly viscous fluids. Furthermore, the numerical results are experimentally validated by investigations of mixing of water-glycerol solutions. The experimental results are found to be in excellent agreement with the numerical data and prove the high mixing efficiency.

Journal Article↗

PubMed1999

Influence of melting and rheological properties of fatty binders on the melt granulation process in a high-shear mixer.

The preparation of granules by melt granulation was investigated using a laboratory-scale high-shear mixer (Pellmix PL 1/8) and binary mixtures containing lactose and different lipidic binders, namely, Compritol 888, Cutina HR, or Precirol ATO5. During the process, the product temperature and the impeller motor power consumption were monitored. On the other hand, the melting behavior (thermal analysis) and the rheological properties (controlled stress capillary rheometer) of the different lipophilic binders were also determined. The granule formation was shown to be quite effective at product temperatures even below the melting point of the lipidic binder, that is, when the binder is sufficiently softened to be deformed by the very high shearing forces developed in the high-shear mixer. On the other hand, the performance of lipidic binders during the melt granulation process was shown to be closely dependent on their melting and rheological properties. The granule growth rate was shown to be higher when the binder melting range is narrow and the influence of temperature on the viscosity of the unmelted product is high.

Calorimetry, Differential Scanning↗

PubMed2001

Scale-up feasibility in high-shear mixers: determination through statistical procedures.

The wet granulation scale-up of a formulation exhibiting plastic deformation behavior under compression was examined. Through experimental factorial design, the effect of solution level, mixing time, and mixer speed on granulation properties was investigated. Measurements of mean particle size, tapped density, bulk density, Carr's index, coarse-to-fine ratio, cumulative percentage, and flow rate were taken and compared among granulations. In addition, comparisons were done on the hardness of tablets made from the formulations. It was shown that the characteristics of the granulations made under different conditions were highly reproducible. The excipient system of microcrystalline cellulose and pregel starch was shown to be a very robust formulation that is resistant to changes in the scaling-up process in high-shear mixers.

Algorithms↗

PubMed2002

The use of mixer torque rheometry to study the effect of formulation variables on the properties of wet granulations.

Mixer torque rheometry was used to investigate the rheological behavior of wet granulations with different concentrations of drug, binder, and water. An experimental design was employed to systematically study the effects of the three formulation variables on the torque profiles of the wet masses over time. Under comparable conditions, increasing binder and water concentrations tended to produce higher wet mass consistencies. Friability of the dried granules was measured as an indication of the strength of the granules. A reduced quadratic model in terms of each of the three variables was found to satisfactorily predict granule friability. Granule friability decreased with increases in the binder level and increased slightly with increasing drug concentration. An inverse relationship was seen between granule friability and the amount of water added to the formulation, especially at lower drug concentrations. Mixer torque rheometry is a useful method for studying the properties of wet granulations when minimal amounts of drug are available for the development of a wet granulated formulation.

Chemistry, Pharmaceutical↗

PubMed2004

Effects of oily drug rheology on content uniformity in granules obtained by wet granulation with a high-shear mixer.

The purpose of the present work was to elucidate the effects of viscosity on the content uniformity of an oily drug in granules obtained by wet granulation with a high-shear mixer. For this purpose, we used d-alpha-tocopheryl acetate diluted with a medium chain fatty acid triglyceride having viscosities in the range from 26.0 to 726.0 mPas. It was found that independent of viscosity, nuclei rich in the oily drug were formed in the process of mixing with powder and that those nuclei prevented uniform distribution of the drug throughout the granules. To achieve content uniformity, it is necessary for the nuclei formed before granulation to be fragmented and for the oily drug to be distributed uniformly throughout granules. Tensile strength of the nuclei was attributed to the viscosity of the oily drug, according to a model for tensile strength of a granule under dynamic conditions. When viscosity of the oily drug increased, tensile strength of the nuclei increased and the extent of the drug demixing in granules was large and constant independent of granulation time. On the other hand, when viscosity of the oily drug decreased, tensile strength of the nuclei decreased. The extent of the drug demixing was small with lower viscosity but increased with a prolonged granulation time. In the case of the oily drug, we found that a decrease in its viscosity led to the improvement of the content uniformity in granules. The viscosity of the oily drug significantly affects its content uniformity in granules by a high-shear mixer granulation.

Drug Compounding↗

PubMed2004

Investigation of the staggered herringbone mixer with a simple analytical model.

An analytical model is presented for the three-dimensional flow in the recently introduced staggered herringbone mixer for microchannels. In this model, the flow in the cross-section of the channel is treated as a lid-driven cavity flow. The model is shown to reproduce the advection patterns that were observed experimentally in the staggered herringbone mixer. The model is then used to study the quality of mixing in this flow as a function of geometry. Analysis is performed with Poincaré maps, mixing simulations, and residence time distributions. A range of optimal geometries is identified.

Complex Mixtures↗

PubMed2005

Does a fast mixer really exist?

In this paper, we are concerned about the limit behavior of the decay rate of variance of a passive and diffusive scalar in a flow field as the diffusivity of the scalar goes to zero. Motivated by the concept of the fast dynamo in the dynamo theory, we term a flow as fast mixer if the decay rate remains away from zero as the diffusivity goes to zero. We first repeat numerical simulations with flow maps and velocity fields used in the existing literature, including the lattice map, the 1D baker's map, and the sinusoidal shear flow. Our simulations shows that, in all cases, the decay rate tends to zero as the diffusivity goes to zero. For the closed flows in a bounded domain, we then theoretically proved this result under certain plausible conditions on the flows. For the open flows in the whole space, we show that the effective diffusivity matrix tends to zero in the limit without the conditions for the closed flow. In conclusion, although a fast mixer might exist, it could be very difficult to find one.

Journal Article↗

PubMed2006

An evaluation of automated blood collection mixers.

BACKGROUND AND OBJECTIVES: We investigated the mixing capacity of two whole blood (WB) collection mixers. MATERIALS AND METHODS: WB was simulated by using a 25% glycerol solution warmed to 35 degrees C. Citrate-phosphate-dextrose (CPD) anticoagulant of a collection system was stained with toluidine blue, and simulated WB was added at 30, 60 or 90 ml/min, respectively (n = 3 per flow speed). The optical density (OD) of 10-ml fractions was measured, and results are expressed as percentage of a well-mixed '100%-sample'. RESULTS: CompoGuard showed adequate mixing at all three flow speeds (average ODs 96-103%). HemoLight showed good mixing at 60 and 90 ml/min (ODs from 97 to 101%). At 30 ml/min, mixing appeared suboptimal, but still conformed to our requirements with ODs from 96% to 104%. CONCLUSION: Both mixers give sufficient mixing of whole blood with anticoagulant.

Anticoagulants↗

PubMed2004

The surface roughness of lactose particles can be modulated by wet-smoothing using a high-shear mixer.

The surface morphology of a-lactose monohydrate particles was modified by a new wet-smoothing process performed in a high-shear mixer using solvents. Successive steps of wetting and drying of lactose powders during rolling in the mixer's cylindrical bowl were performed. Smoothed particles were tested for size distribution, flow, and packing. The wet-smoothing process flattened the surface and rounded the edges of lactose particles. In comparison with original lactose, an improvement of powder packing and flow properties was evidenced. When the process was performed in the presence of a ternary agent such as magnesium stearate, the smoothing was improved. The evolution of rugosity during the smoothing process was assessed through a fractal descriptor of SEM picture. Atomic force microscopy and surface area measurements quantified the surface rugosity. A very significant reduction of the rugosity, more remarkable in the presence of magnesium stearate, was measured. This new process of powder wet-smoothing allows the preparation of lactose particles with different degrees of smoothed surface for the control of flow and packing properties and particle-particle interactions.

Lactose↗

PubMed2001

Melt pelletization of a hygroscopic drug in a high shear mixer. Part 3. Effects of binder variation.

Melt pelletization experiments with sodium valproate as a hygroscopic drug were performed in a laboratory scale high shear mixer. In the current part, the effect of altering the binder liquid properties (using different binders, varying the temperature, or adding highly dispersed silicon dioxide to the molten binder) on the pellet size, size distribution and the growth rate was studied. Three meltable binders, namely glycerol monostearate (GMS), hydrated castor oil (HCO), and polyethylene glycol (PEG), were included in the study. Two series of experiments with GMS or HCO showed a higher granule growth rate with decreasing binder viscosity. Also, increases in the granule growth rate were observed for all meltable binders tested, when the binder amount and the impeller speed were increased. Factorial designs with all three binders were performed under the same conditions. In these experiments, no correlation existed between the granule growth rate and the viscosity of the different binders. The different granule growth rate, however, was mainly attributed to the different solubility of sodium valproate in the binder liquid used. Higher solubility increased the volume of the binder liquid and, accordingly, the granule growth rate. Taking the amount of dissolved drug into account, the granule growth rates of GMS and PEG were comparable. However, HCO displayed a lower granule growth rate, which might be related to its low adhesion tension. During melt pelletization in a high shear mixer the solubility of the drug in the molten binder strongly influences the pelletization process.

Silicon Dioxide↗

PubMed2002

Effect of drug proportion and mixing time on the content uniformity of a low dose drug in a high shear mixer.

The purpose of this study was to investigate the effect of reducing drug proportion and mixing time on the content uniformity of a low dose drug. Buspirone hydrochloride was used as a model drug and was mixed with other ingredients in two different concentrations (0.5% w/w and 5% w/w) in a T. K. Fielder high shear mixer at a high impeller speed (522 rpm) and a high chopper speed (3600 rpm) up to 32 min. Samples were withdrawn from nine locations in the mixer at specific time points using a side-sampling thief probe. The final blends at 32 min were compressed using an instrumented tablet press. Tablets were sampled at the beginning, middle, and end of the compression run. The statistical results indicated that the drug proportion had a significant effect on the content uniformity of the powder blend and the corresponding tablets. For this study, the optimum time to mix the 0.5% w/w formulation was after 8 min while it was only 1 min for the 5% w/w formulation. The RSD of buspirone hydrochloride contents of tablets decreased as the compression run was toward its end. Uniformly mixed blends produced tablets that met the USP XXIV content uniformity requirements.

Analysis of Variance↗

PubMed1977

Oxygen transfer and axial dispersion in an aeration tower containing static mixers.

Oxygen transfer from gas to liquid under steady-state cocurrent flow conditions was modeled using the dispersion model, and the oxygen transfer coefficients were estimated from available data for a column with Koch motionless mixers. The dispersion in the column was estimated for several different gas and liquid flow rates using steady-state tracer experiments. The estimated oxygen transfer coefficients were compared with those estimated using complete mixing and plug flow models. The results indicate that the dispersion model is the most appropriate model for estimating the mass transfer coefficient from the available data.

Absorption↗

PubMed1981

Mixing of pharmaceutical solids. II: Evaluation of multicomponent mixing of cohesive powders in cylindrical shear mixer.

The mixing of three organic carboxylic acids with micronized lactose, all cohesive in nature, was studied using a cylindrical shear mixer. Three mixing indexes (s/sigma A, s/sigma R, and the Ashton-Valentin mixing index) were used to evaluate mixing of the three drugs with lactose. The results suggested that maximum homogeneity was reached after 45 min of mixing. However, different mixing indexes showed different sensitivity to homogeneity of the individual components. The mixing index s/sigma A, which is based on setting standard specifications, appears to provide a better evaluation of homogeneity of individual components compared to the mixing indexes based on complete random mixing theory. The latter did not approach unity for any drug component used in this study. These results suggested that mixing of cohesive powders is a complex process and cannot be explained fully by simple theory based on complete random mixing.

Particle Size↗

PubMed1995

Characterization of wet powder masses with a mixer torque rheometer. 3. Nonlinear effects of shaft speed and sample weight.

We used mixer torque rheometry to examine the effects of shaft speed and sample weight on the rheological behavior of a model wet mass consisting of microcrystalline cellulose and water. Both variables contribute differently to the measured parameters of mean torque and torque range (amplitude). For small weights, the effect of shaft speed is small, but for large weights, shaft speed has a greater effect. For large sample weights, the effect of shaft speed on measured mean torque can be modeled by the Herschel-Buckley model originally developed for concentrated dispersions, enabling yield stresses and viscosities to be calculated. The data generated compare favorably with those measured previously by capillary rheometry.

Cellulose↗

PubMed1986

A gas mixer for computer calibration of an anesthetic mass spectrometer.

To calibrate an anesthetic mass spectrometer without the use of premixed gases and vapors in cylinders, we devised a gas mixer using fixed resistances of capillary needle tubings and adjustable needle valves to dilute test gases and vapors with oxygen. The dilution ratio was determined during each calibration by diluting air with oxygen and noting the reduction in the ratio of nitrogen to oxygen. Empiric correction was made by the computer for the effects of density and viscosity, relative to air, on the flow of nitrous oxide, carbon dioxide, and the saturated vapors of the three anesthetics through the capillary resistor. The computer was programmed to control solenoid valves both for calibration and for the multiplexed sampling of operating rooms. Oxygen, nitrous oxide, and carbon dioxide were used as pure gases, and halothane, enflurane, and isoflurane were vaporized at room temperature in 50-ml vaporizers. The resulting calibrations were found to be accurate to within +/- 2%.

Anesthetics↗

PubMedDate not supplied

Oesophageal motility and digestion of cream liqueurs in combination with common alcohol mixers.

When acidic mixers are added to cream liqueur curdling occurs. Oesophageal motility was studied in normal volunteers during ingestion of this mixture and the effect of combining with gastric juice was assessed in a simulated physiological environment. Twenty-four h ambulatory manometry and pH (n = 22) and gastric studies (n = 7) were carried out. There was no detrimental effect on oesophageal motility. The precipitation is rapidly broken down by the digestive process in the stomach.

Adult↗