Development of dry salbutamol sulfate powder with high inhalation performance independent of inhalation patterns

While dry powder inhalations are commonly used to treat pulmonary diseases, their clinical performance depends on patient inspiratory flow patterns. The purpose of this study was to develop a new powder with high and stable therapeutic performance for various patients. We applied the supercritical antisolvent (SCF) method to salbutamol sulfate (SS) to prepare a bulky SS particle (SS-SCF). Tests of in vitro inhalation performance with a human inspiratory flow simulator revealed SS-SCF to be less susceptible to inspiratory flow patterns than milled SS. When inspired, the unique structure seemed to be broken resulting in small fragments that could be delivered to the lungs. However, stability tests under physical stress showed tolerance for transportation and handling. In addition, optimization of the concentration of the SS solution applied to SCF method improved the in vitro inhalation performance of SS-SCF. These results indicated that a unique bulky SS powder prepared by the SCF method was useful for dry powder inhalation.     

A dopant introduction device for atmospheric pressure photoionization with liquid chromatography/mass spectrometry

This technical note describes in detail the fabrication, operation and characterization of a pneumatically driven dopant introduction device, with a solvent reservoir capacity of 300 mL. Dopant flow rates and stability for this device are governed by the simple regulation of gas pressure rather than the progression of a stepper motor and syringe diameter, as is the case for typical infusion pumps. The device has the potential to provide days or even weeks of continuous, uninterrupted dopant flow at rates commonly adopted for atmospheric pressure photoionization (APPI) experiments without the need to replenish the dopant supply. Although not a refined instrumental design, this device was developed as an alternative cost-effective means of introducing stable dopant flow to an APPI source. The device was designed such that all components would be commercially available and easily procurable from common scientific part vendors. Figures and suggested part numbers are provided to allow those interested to fabricate similar devices to suit their individual experimental needs. Device characterization was performed while monitoring such factors as flow rate calibration, overall flow stability and reproducibility. In addition, a standard mixture of three polycyclic aromatic hydrocarbons was employed as a model sample for a typical reversed-phase liquid chromatography/atmospheric pressure photoionization mass spectrometry (LC/APPI-MS) application in order to demonstrate device performance.     

Controlled generation of submicron emulsion droplets via highly stable tip-streaming mode in microfluidic devices

Submicron emulsions could be produced via the tip-streaming process in a flow-focusing microfluidic device. In this article, the stability of the liquid cone and thread for tip-streaming mode could be significantly improved by employing a three-dimensional flow-focusing device, in which the hydraulic resistance was adjusted by modulating the channel heights in the flow focusing area, orifice, downstream and dispersed phase inlet channel. The pressure range for tip-streaming mode was enlarged significantly compared with two-dimensional flow-focusing devices. Therefore, monodisperse emulsions were produced under this tip-streaming mode for as long as 48 hours. Furthermore, we could control the size of emulsion drops by changing the pressure ratio in three-dimensional flow-focusing devices while the liquid cone was easily retracted during the adjustment of pressure ratio in two-dimensional flow-focusing devices. Furthermore, using the uniform submicron emulsion droplets as confining templates, polyethylene glycol (PEG) particles were produced with a narrow size distribution at the sub-micrometre scale. In addition, magnetic nanoparticles were added to the emulsion for magnetic PEG particles, which can respond to magnetic field and would be biocompatible.     

Development and assessment of a miniaturised centrifugal chromatograph for reversed-phase separations in micro-channels

This paper describes the micro-fabrication and preliminary assessment of a miniature polydimethylsiloxane (PDMS) device for performing rapid, parallel liquid phase chromatographic separations driven by centrifugal force in microchannels. Device components include a main separating channel, into which a high performance liquid chromatography (HPLC) particulate stationary phase was packed under pressure by application of centrifugal force, in addition to solvent and sample reservoirs. Also described are methods for sealing such devices based upon partial polymerisation of PDMS. The mobile phase flow rate through a typical device was measured and several important chromatographic parameters determined from a test separation. An expression describing mobile phase flow through packed channels was also developed, based upon work on liquid flow in open micro-channels. Good agreement between predicted and measured flow rates were observed. Some predictions for potential uses of such devices and possibilities for further miniaturisation are discussed.     

Experimental study of the relative effect of pressure drop and flow rate on the droplet size downstream of a pipe restriction

An experimental setup consisting of a 100?mm inner diameter pipeline, a butterfly valve with inner diameter of 100?mm, and oil and water pumping capacities of up to 20?m³/h were used to study droplet breakup in two-phase oil–water flow. The tests were performed at atmospheric pressure and under ambient temperatures. A particle-sizing camera was used to quantify droplet sizes. Combinations of different flow rates, water cuts, and pressure drops were tested to determine the relative effects of flow rate and pressure drop over a valve on the droplet breakup process. The test matrix was designed so that it should be possible to determine if the droplet sizes produced were independent of the flow rate. The fluid system consisted of a water phase and a mineral oil with viscosity of 4?mPa?·?s. Two different droplet breakup models were compared against the measured droplet sizes. The two models considered turbulence and droplet acceleration through the restriction respectively as the main contributor for droplet breakup.     

Integrated continuous microfluidic liquid-liquid extraction

We describe continuous flow liquid-liquid phase separation in microfluidic devices based on capillary forces and selective wetting surfaces. Effective liquid-liquid phase separation is achieved by using a thin porous fluoropolymer membrane that selectively wets non-aqueous solvents, has average pore sizes in the 0.1-1 microm range, and has a high pore density for high separation throughput. Pressure drops throughout the microfluidic network are modelled and operating regimes for the membrane phase separator are determined based on hydrodynamic pressure drops and capillary forces. A microfluidic extraction device integrating mixing and phase separation is realized by using silicon micromachining. Modeling of the phase separator establishes the operating limits. The device is capable of completely separating several organic-aqueous and fluorous-aqueous liquid-liquid systems, even with high fractions of partially miscible compounds. In each case, extraction is equivalent to one equilibrium extraction stage.     

Controllable preparation of nanoparticles by drops and plugs flow in a microchannel device

Well controlled two-liquid-phase flows in a T-junction microchannel device have been realized. The system of H2SO4 and BaCl2, respectively, in two phases to form BaSO4 nanoparticles was used as a probe to characterize the microscale two-phase flow and transport conditions of a system with interphase mass transfer and chemical reaction. Nanoparticles with narrow size and good dispersibility were produced through drops or plugs flow in the microdevice. As a novel work, the influence of mass transfer and chemical reaction on interfacial tension and flow patterns was discussed based on the experiments. At the same time, the effect of the two-phase flow patterns on the nanoparticle size was also discussed. It was found that the increase of the amount of mass transfer and chemical reaction could change the flow patterns from plugs flow to drops flow. The drop diameter or plug length could be changed in a wide range. Accordingly, a new parameter of mu(0)u(c)/gamma(0)/Q(d) was defined to distinguish the flow patterns. The prepared nanoparticles ranged in size from 10 to 40 nm. Apparently, the particle size decreased with the increase of the drop diameter or plug length. Reasons were discussed based on the mass transfer direction and speed in drops and plugs flow patterns.     

Polyfluorenes minimally doped with 1,4‐bis(2‐thienyl‐2‐cyanovinyl)benzene chromophore: Their synthesis,characterization, and application to white‐light‐emitting materials

Copolyfluorenes ( PFR1 and PFR2 ), chemically doped with 0.1 and 0.025 mol % 2,5‐dihexyloxy‐1,4‐bis(2‐thienyl‐2‐cyanovinyl)benzene (MR chromophere) were synthesized by the Suzuki coupling reaction. The PFR s were used to fabricate white‐light‐emitting devices through incomplete energy transfer. Because of the low content of the MR chromophore, the optical, thermal, and electrochemical properties of the PFR s were almost identical to those of polyfluorene, except for their photoluminescent (PL) and electroluminescent (EL) properties. The copolymer films showed PL peaks at about 428 and 570 nm originating from fluorene segments and MR chromophores, respectively. Compared with the model compound ( MR ), the polymer chains extended the conjugation length of the MR chromophores and exhibited a 20–48 nm red‐shift in the emission band. In addition, the lower LUMO level of the MR (?3.27 eV) was expected to improve the electron injection. The EL devices [ITO/PEDOT:PSS/ PFR s/Ca (50 nm)/Al (100 nm)] showed a broad emission band, covering the entire visible region, with chromaticity coordinates of (0.36, 0.35) and (0.32, 0.30) for PFR1 and PFR2 devices, respectively. The emission color of the PFR2 device was very similar to that of a pure white light (0.33, 0.33); and the maximal brightness and current efficiency were 3011 cd/m² and 1.98 cd/A, respectively, which surpass those found for polyfluorene devices (1005 cd/m², 0.28 cd/A). A). © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3703–3713, 2008     

A method for dynamic system characterization using hydraulic series resistance

The pressure required to drive flow through a microfluidic device is an important characteristic of that device. We present a method to measure the flow rate through microfluidic components and systems, including micropumps and microvalves. The measurement platform is composed of two pressure sensors and a glass tube, which provides series resistance. The principle of the measurement is the fluid dynamical equivalent of Ohm's law, which defines the relationship between current, resistance, and voltage that are analogues to flow rate, hydraulic resistance, and pressure drop, respectively. Once the series resistance is known, it is possible to compute the flow rate through a device based on pressure alone. In addition, the dynamic system characteristics of the device-resistance and capacitance-can be computed. The benefits of this method are its simple configuration, capability of measuring flow rate accurately from the more easily measured pressure, and the ability to predict the dynamic response of microfluidic devices.     

Quantitative modeling of the behaviour of microfluidic autoregulatory devices

We develop a theoretical model for a fluidic current source consisting of a via, a detour channel, and a push-up type micro-valve. The model accurately describes the non-linear behaviour of this type of device, which has been previously measured experimentally. We show how various structural parameters and material properties of the device influence the saturated flow rate and the minimum driving pressure required for the device to function as a current source. Conversely, the model can be used to design a fluidic current source with a desired saturated flow rate and low operational pressure. The present model can be straightforwardly applied to microfluidic circuits composed of many functional autoregulatory devices.     

Development and validation of a RP-HPLC method for simultaneous quantification of bedaquiline (TMC207), moxifloxacin and pyrazinamide in a pharmaceutical powder formulation for inhalation

A reversed phase high performance liquid chromatography (RP-HPLC) method for the simultaneous quantification of bedaquiline (TMC207), moxifloxacin and pyrazinamide in a pharmaceutical powder formulation for inhalation has been developed and validated. The powder was simply dissolved in methanol and the analytes separated in a run time of 20?min on a Luna C18 (2) (150?×?4.6?mm, 5?µm) column using gradient elution with methanol and triethylamine phosphate buffer (pH 2.5) delivered at 1.2?mL/min. The detection (with retention time) was carried out at 269?nm (2.9?min) for pyrazinamide, 296?nm (7.0?min) for moxifloxacin and 225?nm (16.3?min) for bedaquiline, respectively. The method was linear for all analytes in the concentration range 1-100?µg/mL with correlation coefficients >0.998. Lower limits of quantitation (µg/mL) of bedaquiline, moxifloxacin and pyrazinamide were 0.56, 0.43 and 0.24, respectively. The method was accurate (relative error in the range ?0.2 to 2.2) and precise (%RSD ≤6.2) with recovery in the range 100.0–104.7%. The method was successfully applied to determine the drug content and content uniformity of the three analytes in a spray-dried combination powder formulation for inhalation containing L-leucine.     

Direct loading of polymer matrices in plastic microchips for rapid DNA analysis: A comparative study

We report the design and performance validation of microfluidic separation technologies for human identification using a disposable plastic device suitable for integration into an automated rapid DNA analysis system. A fabrication process for a 15-cm long hot-embossed plastic microfluidic devices with a smooth semielliptical cross section out of cyclic olefin copolymer is presented. We propose a mixed polymer solution of 95% w/v hydroxyethylcellulose and 5% w/v polyvinylpyrrolidone for a final polymer concentration of 2.5 or 3.0% to be used as coating and sieving matrix for DNA separation. This formulation allows preparing the microchip without pretreatment in a single-loading step and provides high-resolution separation (≈1.2 bp for fragments <200 bp), which is superior to existing commercial matrices under the same conditions. The hot-embossed device performance is characterized and compared to injection-molded devices made out of cyclic olefin copolymer based on their respective injector geometry, channel shape, and surface charges. Each device design is assessed by fluorescence videomicroscopy to evaluate the formation of injection plugs, then by comparing electropherograms for the separation of a DNA size standard relevant to human identification.     

Optimization and characterization of dry powder of fanhuncaoin for inhalation based on selection of excipients

In this study, dry powder formulations for inhalation of fanhuncaoin, a newly discovered antiinflammatorily active compound isolated from Chinese herb, were designed to optimize the composition and further explore the relationship between the composition, the physical properties and the aerosolization performance. Dry powders were prepared by spray-drying using leucine, chitosan, chitosan oligosaccharide and dipalmitoyl phosphatidylcholine (DPPC) as excipients. Following spray-drying, resultant powders were characterized using scanning electron microscopy, tapped density analysis, laser diffractometry, thermogravimetric analysis and differential scanning calorimetry. The aerosol behaviour of the powders was studied in a Twin Stage Impinger at an airflow rate of 60 l/min using a HandiHaler? inhaler device. Results revealed that the nature and the relative proportion of the excipients greatly influenced the physical characteristics of the powders and their aerodynamic behavior. Among the combinations tested, the composition ratio of fanhuncaoin/leucine/chitosan/chitosan oligosaccharide/DPPC of 10/45/33.75/11.25/0.4 (w/w/w/w/w) prepared in a total solid mass of 1% (w/v) formulation was found to be particularly optimal and exhibited a tapped density of 0.44 g/cm3, an aerodynamic diameter of 2.24 μm and an respirable fraction of 51.29%. In conclusion, optimization of the aerosolization properties of inhalation dry powders could be achieved by appropriately selecting the composition of the particles.     

Development of a wide bore flow through microwave digestion device for the determination of trace metals in soil

A flow through microwave digestion device has been developed for the determination of Cd, Cr, Mn, Ni and Pb in soil by aqua regia extraction. This device differs from existing commercially available devices as it uses a double pumping action to replace the back pressure regulator traditionally used to achieve internal pressurisation. An acid front has also been included to overcome problems associated with the dilution of acid in samples due to dispersion. Recoveries between 95 and 105% of certified values were achieved with standard deviations of less than 4% for certified reference soil (BCR 143R). A sample throughput of 6 samples per hour was achieved in the optimised system. The performance of the device was tested by digesting real soil samples ground through a 250 microns sieve and slurried without the use of surfactants. A comparison of analytical performance for analysing real samples was made between the microwave flow method and a thermal method.     

Sinusoidal crossflow microfiltration device--experimental and computational flowfield analysis

We present an analysis of the flowfield inside a novel crossflow microfiltration device. The filter performance relies on shear focusing by means of a corrugated channel. The flow and shear stress characteristics inside the filter are studied by means of both micro Particle Image Velocimetry (micro-PIV) measurements and Computational Fluid Dynamics (CFD) analysis. We show that an increase of the shear rate by 55-85% as compared to a straight channel geometry is achieved for crossflow velocities ranging from 0.05 m s(-1)-0.8 m s(-1)(Re 5-70). This substantial increase in the local wall shear may improve filter performance in terms of reduced clogging and cell cake formation as compared to conventional crossflow filtration devices. Our current investigation, along with the fact that the filter employs no complex, three dimensional geometrical patterns, advanced pumping schemes, nor has a need for costly assembly and sealing procedures, indicates that the sinusoidal crossflow microfiltration module may serve as a technically and economically feasible solution for integrated lab-on-a-chip devices. Furthermore, the presented approach of shear-focusing may be beneficial in other bio-chemical contexts, such as cell lysis and surface chemistry.     

Synthesis of thermal‐stable and photo‐crosslinkable polyfluorenes for the applications of polymer light‐emitting diodes

Three polyfluorene derivatives which have oxetane‐containing phenyl group at C‐9 position were synthesized via the palladium‐catalyzed Suzuki‐coupling reaction. The synthesized polymers PFB, PFG, and PFR emit blue, green, and red light, respectively. A double‐layer device with the configuration of ITO/PEDOT/polymer/Ca/Al using PFB as the active layer showed a threshold voltage of 5 V, a maximum brightness of 2030 cd/m², and a maximum current efficiency of 0.35 cd/A. Using PFG as the active layer, the device exhibited a threshold voltage of 6 V, a maximum brightness of 6447 cd/m², and a maximum current efficiency of 1.27 cd/A. Using PFR as the active layer, the device showed a threshold voltage of 4 V, a maximum brightness of 2135 cd/m², and a maximum current efficiency of 0.16 cd/A. Better electroluminescent performance was also found based on different design of device structures. Due to photo‐crosslinking property of oxetane groups, the UV‐exposed thin films are insoluble in common organic solvents. A device comprised of blue, green, and red‐emissive pixels was successfully fabricated by spin‐coating and photo‐lithographic processes. In addition, a white light‐emitting device with CIE coordinate of (0.34, 0.33) was achieved by blending PFR into a host material PFB as the active layer. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 516–524, 2010     

Study of flow rate in pressurized gradient capillary electrochromatography using splitter and separation of peptides using an Amide stationary phase

A pressurized gradient capillary electrochromatograph using a splitter was constructed. The variation in flow rate during gradient elution was investigated and separations of peptides using an Amide stationary phase were demonstrated. The flow rate, which is one of the important factors to control chromatographic behavior, was increased during the gradient elution, and the mismatching of mobile phase between the column and the resistance tubing derived three variation patterns in the flow rate. The electrophoretic migration in electrochromatography could enhance in separation of peptides. The separated peak number of tryptic digest of bovine serum albumin was increased from 30 to 40 by the application of +5 kV.     

Investigations of flow field designs in direct methanol fuel cell

An experimental and simulation research had been performed to investigate the performance as well as the flow distribution in the cathode flow field in the case of direct methanol fuel cells (DMFCs). The gas was well distributed in serpentine flow field, whereas stagnation of the gas was observed in parallel flow field. These would contribute to the cell performance greatly due to mass transfer effect when the cells start operating. In addition, the durability test of DMFC was drastically affected in parallel flow field due to poor ability to drain flooded water produced electrochemically at cathode and crossover from anode. In addition, pressure drops of different flow fields were also investigated to evaluate their contribution and feasibility as an economic application for DMFC. DMFC with serpentine flow field featuring higher pressure difference resulted in a larger parasitic energy demand. However, the optimal flow field designs are needed to balance the performance and pressure loss to achieve a uniform fluid distribution and simultaneously minimize energy demand for mass transport. Consequently, flow field with grid pattern appears to be the optimal design for the DMFC cathode.     

Effects of surface heterogeneity on flow circulation in electroosmotic flow in microchannels

The characteristics of electroosmotic flow in a cylindrical microchannel with non-uniform zeta potential distribution are investigated in this paper. Two-dimensional full Navier–Stokes equation is used to model the flow field and the pressure field. The numerical results show the distorted electroosmotic velocity profiles and various kinds of flow circulation resulting from the axial variation of the zeta potential. The influences of heterogeneous patterns of zeta potential on the velocity profile, the induced pressure distribution and the volumetric flow rate are discussed in this paper. This work shows that using either heterogeneous patterns of zeta potential or a combination of a heterogeneous zeta potential distribution and an applied pressure difference over the channel can generate local flow circulations and hence provide effective means to improve the mixing between different solutions in microchannels.     

Dead-end ultrafiltration in hollow fiber modules: Module design and process simulation

Ultrafiltration in a hollow-fiber module operating with outside-in and dead-end flow at a constant flow rate was simulated using a model that takes into account the longitudinal pressure drops inside the fibers and within the fiber bundle. The model considers both the filtration phase during which the membrane is fouled by the formation of a filter cake and the backwash phase in which it is cleaned, so as to predict the net rate of production of the module during an operating cycle.The results show that there is a combination of packing density and fiber diameter that gives a maximum net flow rate. Furthermore, this model allows the influence of operating conditions and feed properties on the module performance to be estimated. This can be used to determine how operating parameters must be modified when there is a change in the feed properties.