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 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. Received 12 March 2000 / Accepted 8 June 2000     

A computational technique for high enthalpy shock tube and shock tunnel flow simulation

A contact discontinuity tracking method with a specially designed moving grid is developed to eliminate the interface smearing completely. In order to precisely locate the contact surface, an updated Riemann solver for unsteady one-dimensional inviscid flows is also developed to allow consideration of the specific heat ratio change across the shock wave. These two new computational techniques are illustrated in a high Mach number shock tube flow field computation. Received 30 October 1997 / Accepted 6 December 1997     

Evolution of shock waves and the primary vortex loop discharged from a square cross-sectional tube

In this paper, a numerical and experimental investigation of the evolution of a transmitting shock wave and its associated primary vortex loop, which are discharged from the open end of a square cross-sectional tube, is described. The experiments were conducted in the square tube connected to a diaphragmless shock tube and the flowfield was visualized from the axial direction with diffusive holographic interferometry. The numerical simulations were carried out by solving the three-dimensional Euler equations with a dispersion-controlled scheme. The numerical results were displayed in the form of interferograms to compare them with experimental interferograms. Good agreement between the numerical and experimental results was obtained. More detailed numerical calculations were carried out, from which the three-dimensional transition of the shock wave configuration from an initial planar to a spherical shape and the development of the primary vortex loop from a square shaped to a three-dimensional structure were clearly observed and interpreted. Received 29 January 1998 / Accepted 22 May 1998     

A new, friction controlled, piston actuated diaphragmless shock tube driver

A new friction operated single piston shock tube driver design that is capable of generating shock waves of Mach number 1.1 to 2 is presented. By using different test gases and evacuating the driven section Mach 5 shock waves can easily be produced. The driver is efficient with shock wave Mach numbers within 9% of that predicted by ideal shock tube theory and the non-dimensional formation length lies between 20 and 40. The brake pad mechanism, that restrains the piston until tests commence, removes the necessity of venting an auxiliary chamber rapidly, thus speeding up the displacement of the piston. It is believed that the design is a practical, simple and cost effective way of generating reproducible shock tube tests with very short test turn around times, while removing the necessity of using a diaphragm and exposing the test gases to the atmosphere. Results for three pistons with masses of 4.4, 0.71 and 0.38 kg (brass, PVC and hollow aluminium respectively) with driver gauge pressures of between 2 and 50 bar (Mach 1.2 to 2) are given. Received 27 February 1998 / Accepted 8 July 1998     

The delivery of particulate vaccines and drugs to human skin with a practical, hand-held shock tube-based system

A unique form of powdered vaccine and drug delivery has been developed. The principle behind the concept is to accelerate vaccine and drug particles, using a gas flow, so that they attain sufficient velocities to enter the skin and achieve a pharmaceutical effect. This paper presents the Contoured Shock Tube (CST), configured to deliver particles to the skin with a narrow and controlled velocity distribution and uniform spatial distribution. The gas and particle flows of a prototype CST are explored experimentally and compared with Computational Fluid Dynamics (CFD) calculations. Some key steps in converting the prototype into a practical hand-held vaccine and drug delivery system are discussed. The ability of this system to deliver particles to the skin is illustrated by sample penetration data into excised human tissue. Received 27 July 2001 / Accepted 1 January 2002     

Advances in detonation driving techniques for a shock tube/tunnel

Early works on the detonation driven shock tube are reviewed briefly. High initial pressure detonable mixture can be used in backward-detonation driver when the buffer tube is attached to the end of the driver for eliminating the excessive reflected peak pressure. Experimental data showed that an improvement on attenuation of the incident shock wave generated by the forward driver can be obtained, provided the diameter of the driver is larger than that of the driven section and an abrupt reduction of cross-section area is placed just beyond the diaphragm. Also, it is clearly verified by a numerical analysis. An additional backward-detonation driver is proposed to attach to the primary detonation driver and on condition that the ratios of initial pressure in the additional driver to that in the primary driver exceed the threshold value, the Taylor wave behind detonation wave in the primary detonation driver can be eliminated completely.     

Nonideal effects behind reflected shock waves in a high-pressure shock tube

Abstract. Shock tubes often experience temperature and pressure nonuniformities behind the reflected shock wave that cannot be neglected in chemical kinetics experiments. Because of increased viscous effects, smaller tube diameters, and nonideal shock formation, the reflected-shock nonidealities tend to be greater in higher-pressure shock tubes. Since the increase in test temperature () is the most significant parameter for chemical kinetics, experiments were performed to characterize in the Stanford High Pressure Shock Tube using infrared emission from a known amount of CO in argon. From the measured change in vibrationally equilibrated CO emission with time, the corresponding ddt (or for a known time interval) of the mixture was inferred assuming an isentropic relationship between post-shock temperature and pressure changes. For a range of representative conditions in argon (24–530 atm, 1275–1900 K), the test temperature 2 cm from the endwall increased 3–8 K after 100 s and 15–40 K after 500 s, depending on the initial conditions. Separate pressure measurements using a shielded piezoelectric transducer confirmed the isentropic assumption. An analytical model of the reflected-shock gas dynamics was also developed, and the calculated 's agree well with those obtained from experiment. The analytical model was used to estimate the effects of temperature and pressure nonuniformities on typical chemical kinetics measurements. When the kinetics are fast (s), the temperature increase is typically negligible, although some correction is suggested for kinetics experiments lasting longer than 500 s. The temperature increase, however, has a negligible impact on the measured laser absorption profiles of OH (306 nm) and CH (216 nm), validating the use of a constant absorption coefficient. Infrared emission experiments are more sensitive to temperature and density changes, so nonuniformities should be taken into account when interpreting ir-emission data. Received 25 April 2000 / Accepted 8 September 2000     

Performance of a shock tube facility for impact response of structures

This paper presents a numerical approach to compute the performance of a double diaphragm shock tube facility for structural response investigations. To assess the influence of different sources of dissipation, including partial diaphragm opening and shock tube vibration, numerical simulations are carried out using several different finite element models of increasing complexity to compute shock tube performance. The numerical model accounting for tearing and partial opening of the diaphragms is the one that best reproduces the results of the experiment, thus indicating that the diaphragm non-ideal opening process is the most relevant cause of losses. Both the numerical and the experimental results agree in predicting shock tube efficiency in terms of intensity of the reflected shock of about 50–60% with respect to ideal, one-dimensional conditions.     

Evaluation of glued-diaphragm fibre optic pressure sensors in a shock tube

Glued-diaphragm fibre optic pressure sensors that utilize standard telecommunications components which are based on Fabry–Perot interferometry are appealing in a number of respects. Principally, they have high spatial and temporal resolution and are low in cost. These features potentially make them well suited to operation in extreme environments produced in short-duration high-enthalpy wind tunnel facilities where spatial and temporal resolution are essential, but attrition rates for sensors are typically very high. The sensors we consider utilize a zirconia ferrule substrate and a thin copper foil which are bonded together using an adhesive. The sensors show a fast response and can measure fluctuations with a frequency up to 250 kHz. The sensors also have a high spatial resolution on the order of 0.1 mm. However, with the interrogation and calibration processes adopted in this work, apparent errors of up to 30% of the maximum pressure have been observed. Such errors are primarily caused by mechanical hysteresis and adhesive viscoelasticity. If a dynamic calibration is adopted, the maximum measurement error can be limited to about 10% of the maximum pressure. However, a better approach is to eliminate the adhesive from the construction process or design the diaphragm and substrate in a way that does not require the adhesive to carry a significant fraction of the mechanical loading.      

Comparison with experiment for TVD calculations of blast waves from a shock tube

Harten's second-order-accurate total-variation-diminishing (TVD) scheme is applied to calculation of flow from the open end of a shock tube. Comparison of numerical results with available experimental data for overpressure at selected points around the shock tube exit shows good agreement. Numerically indicated positions of the moving shock front and Mach stem also compare well with flow shadowgraph data. Where the problem geometry is sufficiently simple and rectangular gridding can be used, Harten's method affords a good choice for blast wave calculations.     

Focusing of a shock wave in a rarefied gas A numerical study

The process of focusing of a shock wave in a rarefied noble gas is investigated by a numerical solution of the corresponding two dimensional initial–boundary value problem for the Boltzmann equation. The numerical method is based on the splitting algorithm in which the collision integral is computed by a Monte Carlo quadrature, and the free flow equation is solved by a finite volume method. We analyse the development of the shock wave which reflects from a suitably shaped reflector, and we study influence of various factors, involved in the mathematical model of the problem, on the process of focusing. In particular, we investigate the pressure amplification factor and its dependence on the strength of the shock and on the accommodation coefficient appearing in the Maxwell boundary condition modelling the gas-surface interaction. Moreover, we study the dependence of the shock focusing phenomenon on the shape of the reflector, and on the Mach number of the incoming shock. Received 25 May 1998 / Accepted 4 January 2000     

The interaction between shock waves and foam in a shock tube

An experimental study and a numerical simulation were conducted to investigate the mechanical and thermodynamic processes involved in the interaction between shock waves and low density foam. The experiment was done in a stainless shock tube (80 mm in inner diameter, 10 mm in wall thickness and 5 360 mm in length). The velocities of the incident and reflected compression waves in the foam were measured by using piezo-ceramic pressure sensors. The end-wall peak pressure behind the reflected wave in the foam was measured by using a crystal piezoelectric sensor. It is suggested that the high end-wall pressure may be caused by a rapid contact between the foam and the end-wall surface. Both open-cell and closed-cell foams with different length and density were tested. Through comparing the numerical and experimental end-wall pressure, the permeability coefficients α and β are quantitatively determined.     

Investigation of high-speed combustible gas ignited by a hot gas jetproduced in the shock tube

The high-speed combustible gas ignited by a hot gas jet, which is induced by shock focusing, was experimentally investigated. By use of the separation mode of shock tube, the test section of a single shock tube is split into two parts, which provide the high-speed flow of combustible gas and pilot flame of hot gas jet, respectively. In the interface of two parts of test sections the flame of jet was formed and spread to the high-speed combustible gas. Two kinds of the ignitions, 3-D “line-flame ignition” and 2-D “plane-flame ignition”, were investigated. In the condition of 3-D “line-flame ignition” of combustion, thicker hot gas jet than pure air jet, was observed in schlieren photos. In the condition of 2-D “plane-flame ignition” of combustion, the delay time of ignition and the angle of flame front in schlieren photos were measured, from which the velocity of flame propagation in the high-speed combustible gas is estimated in the range of 30–90m/s and the delay time of ignition is estimated in the range of 0.12–0.29ms. PACS 47.40.Nm; 82.40.FpPart of this paper was presented at the 5th International Workshop on Shock/Vortex Interaction, Kaohsiung, October 27–31, 2003.     

Transient shock wave flows in tubes with a sudden change in cross section

This paper describes propagation of shock waves within circular cross-section shock tubes with a sudden area change in cross section. A dispersion-controlled scheme was used to solve the Euler equations assuming axisymmetric flows. For experimental visualizations an aspheric cylindrical test section was designed to keep collimated incident light rays parallel once they were reflected or refracted on the inner and outer surfaces of the test section. For effective comparisons with experimental results, equivalent numerical interferograms were constructed to demonstrate effectiveness of the numerical method and verify the observed shock-wave phenomena. The numerical method was used to calculate three further cases with variations of the initial shock-wave Mach number and the flow geometry to clarify the role of these parameters. Complex transient shock-wave phenomena, such as shock-wave reflection, shock/vortex interaction and shock-wave focusing were observed in these cases, and interpreted with shock wave theory. In addition, the research clearly shows that combination of CFD with experiments is effective to highlight physical phenomena in axisymmetric flows. Received 15 June 1996 / Accepted 20 December 1996     

PLIF thermometry in shock tunnel flows using a Raman-shifted tunable excimer laser

Planar laser-induced fluorescence is performed in a free-piston shock tunnel by using a Raman-shifted tunable excimer laser to excite nitric oxide molecules in the flow. Two different flowfields are examined to test the difficulties associated with applying the technique to shock tunnels: the bluff body flow produced by a 25 mm diameter cylinder; and the oblique shock and expansion fan produced by a 35° half-angle wedge. For the cylinder, the maximum flow enthalpy was limited to 4.1 MJ kg due to high flow luminosity which is produced by metallic contaminants in the flow. A reflective filter is used to reduce the influence of flow luminosity making these measurements feasible. Freestream temperature measurements are in excellent agreement with those predicted from numerical flow calculations. Large uncertainties were observed for the high-temperature post-shock results. Several higher enthalpy shots (14 MJ kg) were also performed with the wedge and showed an insignificant amount of contaminant emission. Received 5 June 1996 / Accepted 8 February 1998