Introduction

Hypodermic needles have long been in use as an effective method of transferring drugs into
subcutaneous layers of the human body. However, issues like acquiescence in children and even in some
elders, needle-stick injuries to the vaccinators, cold chain problems in some areas of the world, cost
involved in the purchasing and careful disposal of injections and accidental or intentional reuse of
needles have been some problems in this mode of drug delivery. This in-turn has induced significant
interest from the health care providers, patients and scientific community to develop an alternative
method of drug delivery. This led to the development of Needle-free jet injectors. Delivery of vaccines
into the dermis of human skin with a controlled disruption and dosage can be an appealing replacement
for intramuscular administration of vaccines through needle and syringe. Human skin is rich with tiny
blood vessels and immune network, which can be exploited for a quick dissemination of the in jected
drug with minimal systemic exposure. Alleviation of fear of needles and the associated trauma has been
the main motivation for the development of needle-free, subcutaneous delivery systems for the transfer
of pharmaceutical agents into skin.
Needle-free delivery has already been recognized as a significant challenge and a matter of great
importance. It is quite some time since needle-free jet injectors have come to existence. Since then new
methods incorporating liquid jets have been developed. These devices have not found widespread use
because some are expensive and some are designed for single use. However random incidents of pain
and bruising, cross-contamination because of back-splash, less control and stability on the liquid jet
makes them less precise. These disadvantages offset the advantages of needle-free jet injections against
needles and limited the wide spread use to needle-free jet injectors. In our understanding these issues
arise because of high penetration depths, high velocities, large dose size (20 to hundreds of microliters)
and large diameter nozzles (200-500 micrometers).
Needleless jet injectors, patches with arrays of drug coated micro-projections, ultrasound
permeabilizers to enhance vaccine diffusion into skin, laser and thermal ablation, and abrasive devices.
The needle-free microjet injectors have the advantage of controlled release to the depth of the dermis
with a minimum and recoverable breach of the target. Primarily, the liquid jet preserves most of the
blood vessels and immune network in the target, reducing bleeding and keeping the disseminative
mechanism intact. The minimum breach of the target cells will improve the uptake of drug, enhancing
the effectiveness of drug delivery.
The sophisticated devices coupled with their skilled operators and conducive ambience increase the cost
of operation and may deter their extensive use in developing countries/societies. Economizing the
medical facilities with an intention of extending them to the poor sections of the society has been a
thrust area of research in developing economies and a large component of research has been directed
towards this task. In this backdrop, we developed a shock-wave-driven needleless syringe for delivery of
liquid and colloidal drugs into human skin and soft body targets. The syringe is powered by the impulse
of a shock wave and delivers pulsed liquid jets, in a controlled manner, at a high-speed through a micronozzle. This is a pneumatic device that consumes a few milliliters of driver gas and a stack of soft
diaphragms, both bio-compatible, hence is highly cost-effective.
A new, less expensive and reusable device is needed which will finally allow the full potential of the
needle-free devices to be utilized in large scale immunizations and mass therapeutic drug delivery.

The goal of our research was to prove that such a device could be made and to provide practical means
for powering it.

Device
The device is a 190 mm long syringe with a constant inner diameter of 20 mm and outer diameter of 30
mm, converging into a micro-nozzle of 125 m towards the end. The syringe comprises three
compartments. The first compartment is a compression tube that runs through a length of 110 mm; the
next a shock tube that is 60 mm long, and the third a drug holder that terminates into the micro-nozzle.
All three compartments are bolted together through the flange. The entire device is made of stainless
steel (SS-304). Sufficient factor of safety is considered before designing the device. The compression
tube is attached to the nitrogen gas cylinder through a hose pipe. A valve controller is used to allow the
gas flow from cylinder to compression tube. A thin (0.4 - 1 mm) stack of paper diaphragms (laser tracing
paper 90-95 g/m2 separates the compression and shock tubes, and the drug cavity is isolated from the
shock tube by a 200 m thick rubber diaphragm. Each paper diaphragm is of 60 m thick. A pressure
gauge is connected to the driver section to measure the burst pressure of diaphragm. A circular, rubber
diaphragm was placed on top of the liquid cavity to prevent contamination of the liquid drug and to
avoid spilling of the liquid into the driven section. A vent is provided in the nozzle flange for the nitrogen
gas, which otherwise sustains pressure on the rubber diaphragm that increases the pulse duration of the
jet. Increased pulse duration enhances the mass flow, which affects the control of dosage and the
operation of the device. Nozzle is made using Electric Discharge Machining (EDM). The small diameter of
nozzle is preventing leakage of drug because of surface tension and viscosity effects. Nozzle can be filled
with liquid drug up to the rubber diaphragm. The drug holder can hold a maximum of 1.5 ml. The exit,
inlet diameter of the nozzle is 125 m. The thickness of the rubber diaphragm was 200 m.
Initial set of experiments performed aimed at studying the processes involved in the operation of the
needle-free injection device powered by compressed gas and also at trying to improve the performance
of the device. The goal was to achieve straight flow of liquid jet at maximum possible speed, as well as
achieve repeatability of the experiments. Nitrogen was chosen as a driving gas, in contrast to the helium
used in the normal shock tube devices.

Operation procedure
During the operation, the compression tube is pressurized with ultra-pure nitrogen gas until the rupture
of the stack of paper diaphragms. The rupture of the paper diaphragms launches an incident shock wave
into air (initially at 1 bar pressure) in the shock tube which, on reaching the rubber diaphragm, reflects
back, instantly exerting a high-pressure on the rubber diaphragm. The rubber swiftly undergoes an
elastic deformation into the drug cavity, displacing a controlled volume of drug in the form of a highspeed jet through the micro-nozzle. The drug cavity holds a volume of 1.5 ml. The end of the shock tube
is connected to a miniature dump tank, which acts as a pressure regulator and a silencer during the
operation.

Penetration into gelatin block

To evaluate jet injection, gel models are used for visualization and mimicking of the skin elasticity. Jet
injection consists of three events: jet impingement, flow into skin, and dispersion under skin. Jet impact

creates a hole on the gel with an estimated impact pressure or water-hammer pressure as shown in
figure. The ejected dose is delivered into the gel making a path of jet stream. A thin cylindrical jet of 150
m generated from an injector causes virtually zero splash back at the contact surface allowing smooth
penetration.

Penetration into human skin in-vitro

The in-vitro experiments of jet delivery were performed on a model of human skin kept on top of gelatin
model. The model comprised epidermis and a part of dermis, with an average thickness of 250 m and
gelatin. The stratum corneum of the skin was softened using Savlon solution prior to jet injection. The
liquid of the jet was colored to identify the spot of its penetration into the target. The spots of jet
penetration are presented, where the micrograph indicates the extent of breach of the target during j et
penetration. The jet penetrated through a depth of 20050 m in the skin model, which is the depth of
dermis, which contains skins microcirculation system.
Dehns equations has been used to predict the penetration depth approximately.