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     

Physical methods for genetic transformation of fungi and yeast

The production of transgenic fungi is a routine process. Currently, it is possible to insert genes from other fungi, viruses, bacteria and even animals, albeit with low efficiency, into the genomes of a number of fungal species. Genetic transformation requires the penetration of the transgene through the fungal cell wall, a process that can be facilitated by biological or physical methods. Novel methodologies for the efficient introduction of specific genes and stronger promoters are needed to increase production levels. A possible solution to this problem is the recently discovered shock-wave-mediated transformation. The objective of this article is to review the state of the art of the physical methods used for genetic fungi transformation and to describe some of the basic physics and molecular biology behind them.     

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