Needle-free drug delivery

Needle-free drug delivery was first proposed as early as the mid-19th century and was demonstrated to work many decades ago with one of the first major patents filed by Lockhart in the 1930sJ At first glance, it is a concept both highly attractive and very simple— accelerate a drug formulation (liquid, powder, or depot) so that it penetrates the skin without the requirement for a needle. This avoids a multitude of disadvantages that are inherent in needle use ... 

Lidocaine is absorbed rapidly after parenteral administration and from the gastrointestinal and respiratory tracts. Although it is effective when used without any vasoconstrictor, epinephrine decreases the rate of absorption, such that the toxicity is decreased and the duration of action usually is prolonged. In addition to preparations for injection, an iontophoretic, needle-free drug-delivery system for a solution of lidocaine and epinephrine (lontocaine) is available. This system generally is nsed for dermal procedures and provides anesthesia to a depth of np to 10 mm. 

Needle-Free Drug Delivery Systems. The three types of needle-free drug delivery systems are liquid, powder, and depot injections. Each of these types uses some form of mechanical compression to create enough pressure to force the medication into the skin. Although these needle-free delivery systems cost more initially and require more technical expertise... 

HIV spreads by contact with body fluids, and the common modes of infection include sexual intercourse and contaminated needles used for intravenous drug delivery. Previously, therapeutic use of infected blood and infected breast milk for the baby were also modes of transmission but both have declined due to better screening for blood and AIDS education of expectant mothers. The virus is carried in infected CD4+ T cells, macrophages or as free viruses in blood, semen, vaginal fluids and milk. 

Needle-free injection is an intradermal drug delivery technology that can be considered as a hybrid of transdermal and parenteral technologies. The technology was first proposed in the early twentieth century... 

Powder injection applies many of the principles of pulmonary delivery of dry powders to the lungs The drug has to be in the form of very small particles, is dispensed from a reservoir, and is delivered as an aerosol i.e., particles are dispersed in a gas. Liquid or dissolved drug can be delivered by precipitation or adsorption onto carrier particles. The big difference with pulmonary delivery is the momentum at which the particles are delivered. Driven by a high-pressure helium gas stream, the particles travel fast enough to penetrate the outer layer of the skin, the stratum corneum. The design of devices to deliver needle-free injection of solids was pioneered by researchers at the University of Oxford who founded PowderJect Pharmaceuticals PLC in 1993 (now PowderMed Ltd.) to develop the only powder-based technology so far. Since that... 

Dry-powder inhalers (DPIs) deliver the drug to the respiratory tract in aerosol form. An aerosol is by definition a suspension of free liquid or solid fine particles in a gas phase, which is air in the case of DPIs (and a compressed gas in the case of needle-free injection). The most prominent characteristic that determines the delivery of drug particles to the lungs is the particle size, although particle shape and density are also of considerable importance for the behavior of an aerosol in the respiratory tract (Brain and Blanchard 1993 Gonda 1992 Heyder et al. 1986 Agnew 1984 Heyder et al. 1980). 

Drug delivery via the nasal route offers a number of advantages, the most important of which is the possibility of needle-free treatment. It also means that—in addition to the newly developed peptide- and protein-based drugs—this method is also suitable for a wide variety and perhaps most of the drugs that are currently in use. However, it is not only convenience that sets nasal drug delivery apart This method also provides a rapid onset of action and high bioavailability. 

A drug product can only be successful if it is delivered in a timely manner to the site of action in a way that will be amenable to the patient and in a way to ensure product quality. Different routes of administration may be used to achieve either systemic or local delivery of the protein. Devices such as needle-free injectors and nebulizers may be used to deliver the protein and to enhance patient compliance with use of the drug. Both the route of administration and the decision to use a device are optimally determined early in clinical development of the protein so that there is plenty of clinical experience with the final product. Some... 

Selection of the appropriate route of administration and delivery device is critical for the commercial success of a drug product. Although injections are the most efficient delivery method for proteins, they are not always the most suitable from the patient s perspective. Few routes of administration (IV, IM, SC, pulmonary, and topical for local delivery) have been successful to date with protein therapeutics because of the size and complexity of the protein structure. Consideration of the bioavailability via a given route must be made when determining the dose required. Use of a delivery device such as an implantable pump, needle-free injector, or dry-powder inhaler may yield a product with a commercial advantage over a competitor s product. 

The term needle-free has been used to describe a very wide array of drug delivery technologies, from those that do not have a needle but use electrophoresis... 

The present summary will cover only those technologies where the drug formulation itself is used to penetrate the skin via its mechanical energy. It will not describe any technology where a needle is used to puncture the skin, even if the needle is not visible to the patient or only the epidermis is punctured, such as mini-needles, microneedles, pen injectors, or autoinjectors. Also excluded are systems that ablate the skin mechanically or otherwise disrupt its chemical or mechanical structure to increase its permeability, such as laser ablation, microdermal ablation, electroporation, or iontophoresis. These are usually referred to as transdermal drug delivery, but can also be described as needle free. 

Establishing clinical bioequivalence to a reference delivery method, usually a needle and syringe or an autoinjector or pen injector is the customary method of demonstrating that these conditions have been successfully met. This requires that the maximum blood plasma concentration of the drug (Cmax) and the total area under the time-concentration curve (AUC), as well as their associated confidence intervals, adequately approximate a reference product. The standard criteria to establish bioequivalence are 70-143% for Cmax and 80-125% for AUC (Fig. 3 for an example of a bioequivalent needle-free delivery). 

There are instances of older designs of needle-free injectors that, even with a well-characterized molecule such as insulin, show substantial differences between needle-free and needle delivery. However, improvements in the understanding of the aforementioned principles as well as advancements in the design of needle-free injectors have led to the recent reporting of improved clinical data. Table 1 summarizes an incomplete list of drugs for which there exist clinical data from needle-free administration, all of which demonstrated broadly similar performance between the needle-free system and the needle system (not every report provides sufficient data to determine if bioequivalence was demonstrated). 

King, T. Needle-free injection protein delivery via pre-filled needle-free liquid injection. Drug Delivery Technol. 2003, 3 (7), 52-57. 

Minimally invasive methods of transdermal drug delivery, e.g., needle-free injections... 

Wong, TW, Chen, C.H., Huang, C.C., Lin, C.D. and Hui, S.W. (2006) Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery . J. Control. Release. 110(3), 557-565. 

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