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At least 91 records · Page 5Linked to original sources

Enzyme mass-transfer coefficient in aqueous two-phase systems using static mixer extraction column.

Recent technical advances in aqueous two-phase systems (ATPS) have made this a sound technique for the extraction of biomacromolecules. The extraction of alpha-amylase was investigated using aqueous two-phase systems formed by sodium sulphate-polyethylene glycol (PEG) in water in a 47-mm inner diameter spray column packed with three types of static mixers. The effects of dispersed-phase flow rate, phase composition, column height and diameter were studied. The extraction column was operated in a semi-batch manner. It was found that the hold-up and volumetric mass transfer coefficients increased with an increase in dispersed (PEG-rich) phase velocity and decreased with increasing phase composition. Empirical correlations were developed for fractional dispersed-phase hold-up and volumetric mass transfer coefficients.

Journal Article↗

Mixing enhancement of the passive microfluidic mixer with J-shaped baffles in the tee channel.

This study proposed a new design of a passive micromixer employing several J-shaped baffles in the tee channel to enhance mixing. The mixing performance of the device was investigated experimentally and by numerical simulation. The in-plane structured micromixer was fabricated using micromolding of SU-8 photoresist and PDMS. The mixing performance was demonstrated using image analysis to quantify the concentration distribution in the microchannel. The percentage of mixing increased as the number of baffles increased. The simulated and experimental results showed that the mixer with J-shaped baffles exhibited better mixing performance, and the percentage of mixing was about 1.2 to 2.2 times higher when compared to those without baffles, in the range of Reynolds number (Re) 5 to 350. The improvement in mixing performance was especially apparent at the short axial distance and at the lower Reynolds numbers. The results revealed that the J-shaped baffles could result in lateral convection in the main channel, resulting in improved mixing.

Computer Simulation↗

Isoelectric focusing in immobilized pH gradients: generation and optimization of wide pH intervals with two-chamber mixers.

A new technique for generating extended pH gradients (5 pH units) in Immobiline gels is reported. The previously described (J. Biochem. Biophys. Methods 7, 1983, 123-142) five-chamber gradient mixer has been replaced by a two-vessel device. A single mixture of the available Immobilines (pK 3.6, 4.6, 6.2, 7.0, 8.5 and 9.3) is made, with relative concentrations adjusted so as to produce the most uniform buffering power throughout the desired pH interval. This mixture is then divided into two portions, which are titrated to the extremes of the required pH span with an acidic titrant (Immobiline pK approximately 1) and a basic species (Immobiline pK 9.95). Highly reproducible pH gradients (pH 4-9) are thus generated, which appear extremely useful for the first dimensioned of 2-dimensional techniques. Our previously reported computer program has been implemented with an optimization algorithm which, given any cocktail of Immobilines, automatically adjusts the relative initial concentrations until the smoothest possible beta power is found. For the first time it is possible to perform IEF under controlled physico-chemical parameters: pH span and linearity, beta power, ionic strength and molarity of the buffering species.

Animals↗

Bath-water scalds in children and thermostatic mixer valves.

BACKGROUND: Scalds in children caused by hot bath-water have been virtually eliminated in countries where thermostatic mixer valve (TMV) devices have been introduced. We aimed to determine the frequency and severity of these injuries in our region and estimate reduction in workload and cost if TMVs were introduced in the future. METHODS: A retrospective review was conducted of case-notes for all bath-water scalds patients aged under 16 years, admitted to the Northern Regional Burn Centre from the 1 January 1997 until 1 January 2005. RESULTS: One hundred and twenty-five patients were admitted over this period. Their average+/-S.D. age was 35.7+/-27.23 months. Scalds ranged from 0.5 to 45% total burn surface area (mean 9.3+/-9.15%). These patients stayed in hospital for an average of 6.3+/-5.58 days and 18 (14.4%) required tangential excision and split skin grafting. DISCUSSION: These injuries are: painful, psychologically disturbing and potentially preventable. The care of these children has significant cost implications, which could be reduced with the introduction of proposed legislation to enforce the installation of TMVs into all newly built houses. We are in favour of such legislation to prevent any further unnecessary suffering and cost arising from these accidents.

Adolescent↗

Characterization and taste-masking evaluation of acetaminophen granules: comparison between different preparation methods in a high-shear mixer.

The aim of this study was to prepare and to investigate acetaminophen taste-masked granules obtained in a high-shear mixer using three different wet granulation methods (method A: water granulation, method B: granulation with a polyvinylpyrrolidone (PVP) binding solution and method C: steam granulation). The studied formulation was: acetaminophen 15%, alpha-lactose monohydrate 30%, cornstarch 45%, polyvinylpyrrolidone K30 5% and orange flavour 5% (w/w). In vitro dissolution studies, performed at pH 6.8, showed that steam granules enabled the lower dissolution rate in comparison to the water and binding solution granules; these results were then confirmed by their lower surface reactivity (D(R)) during the dissolution process. Moreover, the results of the gustatory sensation test performed by six volunteers confirmed the taste-masking effects of the granules, especially steam granules (P<0.001). Morphological, fractal and porosity analysis were then performed to explain the dissolution profiles and the results of the gustatory sensation test. Scanning electron microscopy (SEM) analysis revealed the smoother and the more regular surface of steam granules with respect to the samples obtained using methods A and B; these results were also confirmed by their lower fractal dimension (D(s)) and porosity values. Finally, differential scanning calorimetry (DSC) results showed a shift of the melting point of the drug, which was due to the simple mixing of the components and not to the granulation processes. In conclusion, the steam granulation technique resulted a suitable method to comply the purpose of this work, without modifying the availability of the drug.

Acetaminophen↗

Self-emulsifying pellets prepared by wet granulation in high-shear mixer: influence of formulation variables and preliminary study on the in vitro absorption.

A method of producing self-emulsifying pellets by wet granulation of powder mixture composed of microcrystalline cellulose, lactose and nimesulide as model drug with a mixture containing mono- and di-glycerides, polisorbate 80 and water, in a 10-l high shear mixer has been investigated. The effects of the formulation variables on pellets characteristics were evaluated by mixtures experimental design and by a polynomial model, in order to describe the phenomenon, to verify eventual interactions among components of the mixture and to investigate the feasibility of scaling-up. After determination of size distribution, the pellets were characterised by scanning electron microscopy, dissolution and disintegration tests, and by in vitro absorption test Such an approach, applied to the development of a self-emulsifying system for nimesulide as poorly water-soluble model drug, resulted in different formulations with improved drug solubility and permeability characteristics. The data demonstrate that pellets composed of oil to surfactant ratio of 1:4 (w/w) presented improvement in performance in permeation experiments.

Absorption↗

Preparation in high-shear mixer of sustained-release pellets by melt pelletisation.

The preparation of sustained-release pellets by melt pelletisation was investigated in a 10-l high shear mixer and ternary mixtures containing stearic acid as a melting binder, anhydrous lactose as a filler and theophylline as a model drug. A translated Doehlert matrix was applied for the optimisation of process variables and quality control of pellets characteristics. After determination of size distribution, the pellets were characterised with scanning electron microscopy, X-ray photoelectron spectroscopy and porosimetric analysis. Finally, the in vitro release from every single size fraction was evaluated and the release mechanism was analysed. Since the drug release rate decreased when enhancing the pellet size fraction, the 2000-microm fraction, exhibiting a substantially zero-order release, was selected for further in vivo biovailability studies. These data demonstrated that pellets based on the combination of stearic acid and lactose can be used to formulate sustained release pellets for theophylline.

Adult↗

Study of effect of excipient source variation on rheological behavior of diltiazem HCl-HPMC wet masses using a mixer torque rheometer.

In the wet massing of powders and powder blends, the rheological behavior of the wet powder masses not only plays a critical role in the unit process but also influences the attributes of the product. The physical properties of the powder excipients, such as particle size and size distribution, shape, surface area, bulk and tapped density and surface morphology, are a major source of variability in the rheological behavior of wet powder masses and the quality attributes of the final product. The objective of the present investigations was to study the rheological behavior of wet masses containing hydroxypropyl methylcellulose (HPMC) obtained from two sources (Methocel from Dow and Pharmacoat from Shin-Etsu) using a mixer torque rheometer. In order to simulate a real formulation, diltiazem HCl (DTZ) (40% loading) was used as part of the substrate powder mass. Hydroxypropyl cellulose (HPC) was used as the binder. Since HPMC is water-soluble, isopropyl alcohol (IPA) was used as the wet massing liquid. The rheological behavior of the wet powder masses was studied as a function of mixing time and amount of wet massing liquid (IPA). The rheological profiles obtained for DTZ-Methocel and DTZ-Pharmacoat exhibited same magnitude for mean torque, however, for DTZ-Pharmacoat the peak was more extended than that for DTZ-Methocel. The extended peak for DTZ-Pharmacoat indicated that the wet mass will stay suitable during the process for larger quantities of the wet massing liquid before turning into paste and becoming unsuitable for the process as compared with the DTZ-Methocel system. The mixing kinetics of the two powder systems appeared to be quite different. These differences in the rheological behavior of the wet masses may be attributed to the difference in the particulate and surface properties of the two HPMCs. Some of the properties of the two HPMCs, such as particle size and size distribution, surface area, surface morphology and DSC thermograms, explain the difference observed in their rheological behavior. The difference in the rheological profiles of the two DTZ-HPMC systems indicated superiority of Pharmacoat over Methocel considering their wet massing behavior.

Calorimetry, Differential Scanning↗

Relationship between inhomogeneity phenomena and granule growth mechanisms in a high-shear mixer.

A poorly understood phenomenon observed during high-shear granulation is the poor distribution of a drug in the granulate. To investigate the causes of this inhomogeneity, lactose of three different particle sizes was granulated with 0.1% micronized estradiol (5 microm) in a 10 l high-shear mixer. An aqueous solution of HPC was used as binder. Granulation with the largest lactose particles (141 microm) yielded a homogeneous granulate. However, at a prolonged process time demixing was observed. Contrary to the largest particles, granulation with the smaller lactose particles (50 and 23 microm) already leads to demixing in the first minute, although to a lesser extent. It was concluded that granulation with the largest particles resulted in breakage behavior of the granulate, thereby preventing demixing. However, once granules are strong enough (smaller particle size and prolonged process time) to survive the shear forces demixing is observed. Theoretical calculations of dynamic and static granule strength were used to explain the influence of lactose particle size and process time on breakage behavior. It was argued that once granules survive, preferential growth of the small estradiol particles in favor of the larger lactose particles causes the demixing. The extent of demixing depends on the particle size difference.

Chemistry, Pharmaceutical↗

The preparation of agglomerates containing solid dispersions of diazepam by melt agglomeration in a high shear mixer.

The aim of this study was to prepare by melt agglomeration agglomerates containing solid dispersions of diazepam as poorly water-soluble model drug in order to evaluate the possibility of improving the dissolution rate. Lactose monohydrate was melt agglomerated with polyethylene glycol (PEG) 3000 or Gelucire 50/13 (mixture of glycerides and PEG esters of fatty acids) as meltable binders in a high shear mixer. The binders were added either as a mixture of melted binder and diazepam by a pump-on procedure or by a melt-in procedure of solid binder particles. Different drug concentrations, maximum manufacturing temperatures, and cooling rates were investigated. It was found to be possible to increase the dissolution rate of diazepam by melt agglomeration. A higher dissolution rate was obtained with a lower drug concentration. Admixing the binders by the melt-in procedure resulted in similar dissolution rates as the pump-on procedure. The different maximum manufacturing temperatures and cooling rates were found to have complex effects on the dissolution rate for formulations containing PEG 3000, whereas only minor effects of the cooling procedure were found with Gelucire 50/13. Gelucire 50/13 resulted in faster dissolution rates compared to PEG 3000.

Diazepam↗

Rheological characterization of microcrystalline cellulose and silicified microcrystalline cellulose wet masses using a mixer torque rheometer.

The rheological properties of silicified microcrystalline cellulose (Prosolv 50) were compared with those of standard grades of microcrystalline cellulose (Emcocel 50 and Avicel PH 101). Cellulose samples were analyzed using nitrogen adsorption together with particle size, flowability, density and swelling volume studies. The rheological behaviour of the wet powder masses was studied as a function of mixing time using a mixer torque rheometer (MTR). Silicified microcrystalline cellulose exhibited improved flow characteristics and increased specific surface area compared to standard microcrystalline cellulose grades. Although the silicification process affected the swelling properties and, furthermore, the mixing kinetics of microcrystalline cellulose, the source of the microcrystalline cellulose had a stronger influence than silicification on the liquid requirement at peak torque.

Cellulose↗

[Hypoxia secondary to the failure of an oxygen-air-nitrous oxide mixer].

A case is reported of hypoxia occurring during anaesthesia in a spontaneously breathing ASA I patient. The patient became cyanotic twice when breathing a gas mixture delivered by a safety mixer. Changing the machine solved the immediate problem. The diagnosis was difficult to make because the rotameters all showed normal delivery of oxygen and nitrous oxide. Oximetry elucidated the cause, which was found to be a defective rapid oxygen control. Because these machines do not appear to be absolutely reliable, the use of gas analysers should become more systematic.

Adult↗

Acrylic bone-cement. Influence of mixer design and unmixed powder.

The effects of hand mixing with two different mechanical mixing systems (fixed versus rotating central axis) on unmixed powder content, macroporosity, density, and bending strength of acrylic bone-cement are compared. The effects of voids and unmixed powder on cement bending strength are also evaluated. In acrylic cement, both unmixed powder monomer and voids 1 mm and larger can be easily visualized and analyzed on radiographs of 3-mm-thick samples. Image analysis allowed demonstration of a significant increase in unmixed powder content (P < .0001), in cement prepared using a vacuum mixing system with a fixed central axis compared with both the rotating axis system and hand mixing. The rotating-axis system produced cement of higher density compared with hand mixing only (P = .004). There was a significant correlation between the number of voids measured per square centimeter and cement bending strength (P < .0001), as well as an independent and significant correlation between unmixed powder content and cement bending strength (P < .0001). Mechanical mixing using a fixed central axis produced significantly weaker cement compared with both hand mixing (P < .015) and the rotating-central-axis system (P < .0001). A 15% drop in strength between the two mechanical mixing systems was observed. It is therefore concluded that the use of different rotating systems in mechanical mixers can influence void and unmixed powder content and, consequently, the mechanical properties of acrylic cement, and that unmixed powder is an independent factor affecting the bending strength of the cement.

Acrylates↗

Effects of interactions between powder particle size and binder viscosity on agglomerate growth mechanisms in a high shear mixer.

A study was performed in order to elucidate the effects of the interactions between powder particle size and binder viscosity on the mechanisms involved in agglomerate formation and growth. Calcium carbonates having mean particle sizes in the range of 5-214 microm and polyethylene glycols having viscosities in the range of approximately 50-100000 mPas were melt agglomerated in a high shear mixer. Agglomerate growth by nucleation and coalescence was found to dominate when agglomerating small powder particles and binders with a low viscosity. Increasing the binder viscosity increased the formation of agglomerates by immersion of powder particles in the surface of the binder droplets. With a larger powder particle size, an increasing binder viscosity was necessary in order to obtain an agglomerate strength being sufficient to avoid breakage. Due to a low agglomerate strength, a satisfying agglomeration of very large particles (214 microm) could not be obtained, even with very viscous binders. The study demonstrated that the optimum agglomerate growth occurred when the agglomerates were of an intermediate strength causing an intermediate deformability of the agglomerates. In order to produce spherical agglomerates (pellets), a low viscosity binder has to be chosen when agglomerating a powder with a small particle size, and a high viscosity binder must be applied in agglomeration of powders with large particles.

Adhesiveness↗

Melt pelletisation of a hygroscopic drug in a high shear mixer. Part 2. Mutual compensation of influence variables.

The process of melt pelletisation in a Diosna P10 high shear mixer was examined for sodium valproate and glycerol monostearate. The effects of binder concentration, impeller speed and massing time on mean granule size, size distribution and liquid saturation were investigated. Spherical pellets of almost similar size and size distribution were obtained after 20 min of massing time, with a binder content from 3.1 to 14.1% w/w by adjusting the impeller speed. Granule growth was observed at low levels of binder concentration and liquid saturation (<80%) which is untypical for melt granulation. The liquid saturation seemed to have no major influence on the final pellet size. Additional, mutually compensating effects on granule growth were found to be impeller speed and massing time for a fixed binder concentration. Low levels of both, binder concentration and impeller speed, allowed for good control of the process. The amount of water adsorbed by the hygroscopic drug was found to accelerate granule growth.

Absorption↗

Melt pelletization in high shear mixer using a hydrophobic melt binder: influence of some apparatus and process variables.

The effects of process conditions and the apparatus variables on the granulometric characteristics of a formulation containing a hydrophobic binder (stearic acid), lactose and paracetamol prepared by melt pelletization process were investigated in a 10-litre high shear mixer. The factors under investigation were: impeller speed, massing time, type of impeller blades and presence of the deflector and their reciprocal interactions. Two granule characteristics were analysed: the percentage of aggregates larger than 3000 microm (Y(1)) and the yield of the 2000-microm pellet size fraction (Y(2)). In order to estimate simultaneously the above-mentioned factors, a particular experimental design was adopted, that allowed the reduction of the number of trials from 378 to 35 and took into consideration other uncontrolled factors with the aid of a block variable. Using the postulated model, we found the optimal operating conditions to minimize Y(1) and increase Y(2) by selecting the type of impeller, and by using an impeller speed lower than 300 rpm, a massing time of 8-9 min and by not using the deflector. Finally, the validity of the adopted strategy has been proved with an additional check point.

Acetaminophen↗

Stopped-flow enzyme assays on a chip using a microfabricated mixer.

This paper describes a microfabricated enzyme assay system including a micromixer that can be used to perform stopped-flow reactions. Samples and reagents were transported into the system by electroosmotic flow (EOF). Streams of reagents were merged and passed through the 100-pL micromixer in < 1 s. The objective of the work was to perform kinetically based enzyme assays in the stopped-flow mode using a system of roughly 6 nL volume. Beta-galactosidase (beta-Gal) was chosen as a model enzyme for these studies and was used to convert the substrate fluorescein mono-beta-D-galactopyranoside (FMG) into fluorescein. Results obtained with microfabricated systems using the micromixer compared well to those obtained with an external T mixing device. In contrast, assays performed in a microfabricated device by merging two streams and allowing mixing to occur by lateral diffusion did not compare well. Using the microfabricated mixer, Km and kcat values of 75 +/- 13 microM and 44 +/- 3 s(-1) were determined. These values compare well to those obtained with the conventional stopped-flow apparatus for which Km was determined to be 60 +/- 6 microM and kcat was 47 +/- 4 s(-1). Enzyme inhibition assays with phenylethyl-beta-D-thiogalactoside (PETG) were also comparable. It was concluded that kinetically based, stopped-flow enzyme assays can be performed in 60 s or less with a miniaturized system of roughly 6 nL liquid volume when mixing is assisted with the described device.

Clinical Enzyme Tests↗

A capillary mixer with adjustable reaction chamber volume for millisecond time-resolved studies by electrospray mass spectrometry.

A novel continuous-flow apparatus for on-line kinetic studies of (bio)chemical solution-phase processes by electrospray ionization mass spectrometry (ESI-MS) is described. The device is based on two concentric capillaries. Fluid is released from the inner capillary into the intercapillary space, where it mixes with solution flowing through the outer capillary, thus initiating the reaction of interest. Gas-phase analyte ions are formed near the tip of the outer capillary by pneumatically assisted ESI. This setup allows the mixer to be placed directly within the ion source, thus providing a minimal dead volume of ~8 nL. Time-resolved data can be recorded in both "spectral" and "kinetic" modes. In the former case, the position of the inner capillary is fixed at various points, such that entire mass spectra can be recorded for selected reaction times. For experiments in kinetic mode, the mass spectrometer monitors the signal intensity at selected m/z values, while the inner capillary is continuously pulled back, thus providing intensity-time profiles for specific reactive species. A theoretical framework is developed that allows the measured kinetics to be analyzed by taking into account the effects of laminar flow within the reaction capillary. Failure to take these effects into account results in erroneous rate constants. Studies on the demetalation kinetics of chlorophyll reveal that the apparatus can reliably measure rate constants up to at least 100 s-1. This represents a substantial improvement over previous ESI-MS-based kinetic methods. Spectral mode experiments on the refolding of ubiquitin show the changing proportions of denatured and tightly folded protein subpopulations in solution. When monitored in kinetic mode, the refolding process was found to proceed with a rate constant of 5.2 s-1.

Journal Article↗