Brian John Bellhouse

On flow through furrowed channels. Part 2. Observed flow patterns

Observations of flow in furrowed channels support the calculations of part 1 (Sobey 1980). If the mainstream flow is steady there is a critical Reynolds number below which separation does not occur. Above that Reynolds number vortices form and fill the furrow. When the mainstream is oscillatory, the flow may separate during the acceleration to form strong vortices. During the deceleration the vortices grow to fill the furrow and channel. As the mainstream reverses the vortices are ejected from the furrows as the fluid flows between the wall and the vortex. Photographs show that this pattern occurs for sinusoidally varying walls, furrows that are arcs of circles and rectangular hollows.

Investigations of gas and particle dynamics in first generation needle-free drug delivery devices

Abstract. Transdermal powdered drug delivery involves the propulsion of solid drug particles into the skin by means of high-speed gas-particle flow. The fluid dynamics of this technology have been investigated in devices consisting of a convergent-divergent nozzle located downstream of a bursting membrane, which serves both to initiate gas flow (functioning as the diaphragm of a shock tube) and to retain the drug particles before actuation. Pressure surveys of flow in devices with contoured nozzles of relatively low exit-to-throat area ratio and a conical nozzle of higher area ratio have indicated a starting process of approximately 200

A ballistic study of micro-particle penetration to the oral mucosa

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Screw-thread flow promoters: an experimental study of ultrafiltration and microfiltration performance

s typical duration, followed by a quasi-steady supersonic flow. The velocity of drug particles exiting the contoured nozzles was measured at up to 1050 m/s, indicating that particle acceleration took place primarily in the quasi-steady flow. In the conical nozzle, which had larger exit area ratio, the quasi-steady nozzle flow was found to be overexpanded, resulting in a shock system within the nozzle. Particles were typically delivered by these nozzles at 400 m/s, suggesting that the starting process and the quasi-steady shock processed flow are both responsible for acceleration of the particle payload. The larger exit area of the conical nozzle tested enables drug delivery over a larger target disc, which may be advantageous.

Effect of liquid pulsation on protein fractionation using ultrafiltration processes

This paper describes the results of an investigation into the impact of model micro-particles to ex vivo buccal mucosa (the cheek) of pigs and beagle dogs. The work is aimed at optimizing a unique form of pharmaceutical delivery. The pharmaceutical is formulated into particle form and accelerated toward the target of skin or mucosa by using a gas jet. In this study, research devices designed using analytical, computational (computational fluid dynamics) and experimental methodologies were used to deliver particles at uniform and predetermined velocities. These velocities were confirmed using light obscuration, pressure measurement and particle image velocimetry methods. Polystyrene, glass, stainless steel and gold micro-particles at a range of size distributions were used for the payloads for injection using these devices. Injection occurred with a wide range of impact conditions into fresh canine (dog) and porcine (pig) buccal mucosa. Final positions of the particles were determined from histological sections and the results analyzed in relation to the known particle impact parameters of size, density and velocity. The experimental results are collated using an empirical term, based on particle impact parameters. Comparison is then made to a semi-empirical penetration model. This is done by analysing the penetration results in terms of each particle impact parameter. Analysis shows that this model fits the experimental data well when reasonable estimates of the tissue mechanical properties are chosen

Bioavailability following transdermal powdered delivery (TPD) of radiolabeled inulin to hairless guinea pigs

Abstract The screw-thread flow promoters presented in this work are designed to enhance filtration in a tubular geometry using a standard half-inch diameter. Two separate experimental studies were undertaken to evaluate the ultrafiltration of BSA and the microfiltration of bovine blood. The convective mixing in each system was augmented through a combination of two vortex patterns: helical flow around a semi-circular cross section and flow through a sudden expansion. The screw-threads are simple to construct and operate well under laminar, quasi-steady flow conditions such that scale-up and the processing of shear sensitive fluids should be possible. The internal screw-thread generated 75% of the clean water flux at a high BSA concentration of 60 g/l. The superposition of an oscillatory flow component on the mean flow did not significantly improve the performance. The internal screw-thread design performed poorly when applied to the separation of plasma from whole blood because the centrifugal forces appeared to complement concentration polarization. An external screw-thread design was found to be an effective anti-fouling technique and tripled the microfiltration performance relative to an internal screw-thread. The lower pitch of 3.5 mm gave a plasma flux of order 0.1 cm/ min, moderate flux decline and no signs of haemolysis.

Enhanced microfiltration of bovine blood using a tubular membrane with a screw-threaded insert and oscillatory flow

Abstract The present study consists of an experimental evaluation of an ultrafiltration (UF) module for protein fractionation using pulsations. A flat-plate ultrafilter equipped with a ladder-like flow deflector is used to perform partial separation of γ-globulins from albumin in bovine plasma. The results of two separate sets of experiments are reported in which two different kinds of pulsations, i.e. retentate side flow pulsation and transmembrane pressure pulsation, are employed. In the case of a single protein solution (bovine serum albumin), vortex wave mixing produces a marked reduction in sieving coefficient, and hence causes concentration of the protein solution. When bovine plasma is ultrafiltered, the passage of both γ-globulins and albumin is highly restricted. This problem is tackled by the application of transmembrane pressure pulsation which leads to enhanced selectivity of the ultrafiltration membrane for the albumin protein.

Numerical and experimental analysis of a high speed needle-free powdered vaccine delivery device

Abstract Transdermal powdered delivery (TPD) is a novel method for needle-free administration of drugs, vaccines, and other therapeutic compounds. In this study, the efficiency of the TPD method has been evaluated following delivery of radiolabeled inulin to hairless guinea pigs. The quantity of radioactive inulin excreted in the urine, as a percentage of the total amount delivered, has been used as a measure of bioavailability. Maximum urine recoveries of radiolabeled inulin (mean±SE) for TPD were 32.8±3.7% when the site was unwashed following injection and when large inulin particles (39–52 μ m) were used. Washing the injection site immediately following inulin administration resulted in decreased recovery levels (12.2±1.3%) for the same sized particles. Delivery of smaller inulin particles (21–24 μ m) with no post-injection washing of the site resulted in a reduced urine recovery levels (10.8±4.1%) over that obtained with the larger particles. For comparison, subcutaneous injection of a similar dose resulted in recovery levels of 88.9±3.6%. Inulin residue within the prototype PowderJect ® device used for these experiments was shown to be approximately 17% of the starting dose. A small but acceptable degree of skin damage (erythema) at the injection site was seen following administration of the compound.

Enhancement of plasma filtration using the concept of the vortex wave

This paper reports the performance of a new plasma filter which consists of a tubular membrane containing a concentric screw-threaded insert. Bovine blood was used as the working fluid, which was pumped through the annular space between the insert and the tubular membrane in oscillatory flow with a mean component. The effects of pulsation frequency and piston stroke length were investigated. Membranes of 0.2 and 0.45 μm pore sizes were tested. For the range of Strouhal number 0.0018-0.0003 in the predominantly laminar flow regime, it was found that there was a linear relationship between the bovine plasma flux and the inverse of the Strouhal number. Haemolysis, measured by the concentration of free plasma haemoglobin, proved to be insignificant. Due to the depolarizing influence of the flow pattern induced by pulsations, protein recovery was close to 100%.

Characterization of powdered epidermal vaccine delivery with multiphoton microscopy.

A unique form of powdered vaccine delivery system, the PowderJect particle delivery system, has been developed. The principle of the system is to accelerate the vaccine in micro-particle form by a gas flow behind a travelling shock wave, so that they can attain sufficient momentum to penetrate the skin and thus achieve a pharmacological effect. One of the most recent developments is the Contoured Shock Tube (CST), configured to deliver powdered vaccine particles to the skin with a narrow and highly controllable velocity distribution and a uniform spatial distribution. In this paper, Computational Fluid Dynamics (CFD) has been utilised to simulate the complete operation of a CST high velocity delivery system. The key features of the gas dynamics and gasparticle interaction are discussed.