Innovative Injection Use Research Paper
Needle free injection systems are innovative ways to introduce a variety of medicines in patients without piercing the skin with a traditional needle. This systems work by the mechanism in which liquid medication is forced at a high speed through a tiny orifice that is held against the skin. Due to this an ultra fine stream of high pressure fluid is created, that penetrates the skin without the use of a needle, thus faster administration of drug occurs as compared to conventional needles. They are present in the form of power sprays, edible products, inhalers, and skin patches. Needle free systems are designed to solve the problems created due to conventional needles making them safer, less expensive, and more convenient. It is expected that these systems will augment the rate of vaccination and reduce the amount of antibiotics prescribed. Moreover, they should decrease the number of needle stick accidents that have been seen in some health care workers contracting diseases. Today, they are a increasingly rising technology that promises to make the administration of medicine more efficient and less painful. Companies are not only working on developing devices that are safer and easier to use, but also on alternatives which can deliver even more types of medicines.Innovative Injection Use Research Paper
Keywords: Needle, Free injection, drug delivery.
INTRODUCTION:
Generally injections are given to people to protect them from various diseases such as influenza, tetanus, cholera, typhoid, and other diseases. When a needle is inserted through the skin, the vaccine or drug it carries provides systemic immunity. This is due to the fact that the vaccine gets into the bloodstream and provokes the body to generate antibodies that are carried throughout the entire body. Unfortunately, there are a variety of problems related with the hypodermic needles used for these injections. One of the most significant drawbacks is the relatively high cost of the needles. The cost results in a lower vaccination rate, especially for children in developing countries. Another problem with traditional needles is the lack of re usability. If a needle syringe is not sterilized, reusing it can lead to the spread of disease. Additionally, many people have a fear of needles which causes them to avoid treatment. These drawbacks have led to the development of alternative delivery systems to needle injections. Needle free systems are designed to solve the above problems making them safer, less expensive, and more convenient. It is expected that these systems will increase the incidence of vaccination and reduce the amount of prescribed antibiotics. Moreover, they should reduce the number of needle stick accidents that have resulted in some health care workers contracting diseases. More than a dozen companies have developed alternatives to needle injections. Some of the different designs include nasal sprays, nose drops, flavored liquids, skin patches, air forced and edible vaccine packed vegetables. The needle free systems that are most like traditional injections involve the direct transfer of the medicine through the skin. Nasal sprays, suppositories, and eye and nose drops are forms of needle free systems that deliver medications through the mucous membrane, where 90% of all infections occur. The mucous membrane is found throughout the body and includes the lining of the respiratory tract, digestive tract, and urinary and genital passages. These needle free systems prompt the body to produce both antibodies at the mucosa surfaces and system wide. The nasal shot may be the first needle free flu shot. It is a syringe like device that has an aerosol sprayer substituted for the needle. It delivers a weak flu virus directly to the nasal passages and creates immunity to the flu with minimal side effects. Inhalers are another type of needle free delivery system.Innovative Injection Use Research Paper
HISTORY
As long as drugs have been known to alleviate diseases, people have searched for enhanced methods of delivering them. During the early nineteenth century researchers made several discoveries that ultimately led to the development of the hypodermic needle by Alexander Wood in 1853. This device was used to give morphine to patients who were suffering from sleeping disorders. In following years, the hypodermic needle underwent major changes which made them more convenient to use, safer, and more consistent. However, needles still have major drawbacks which prompted researchers to find needle free alternatives. The first air powered needle free injection systems were developed during the 1940s and 1950s. Over the years, these devices have been modified in order to improve the amount and types of medicines delivered, and the effectiveness and the ease of use.
STRUCTURE OF HUMAN SKIN
Knowledge of the structure of skin is essential for successful administration of drugs through needle free injection systems as these drugs are administered beneath the skin. Human skin is generally made of two layers i.e., epidermis and dermis.
Epidermis: It is the outermost layer of the skin. A waterproof, protective wrap over the body’s surface is formed due to the epidermis; it is made up of stratified squamous epithelium with an underlying basal lamina. The epidermis has no blood vessels, and cells in the deepest layers are nourished by means of diffusion from blood capillaries which extend to the upper layers of the dermis. Merkel cells, keratinocytes, melanocytes and Langerhans cells are the main type of cells which form the epidermis. The epidermis can be further subdivided into various strata such as (beginning with the outermost layer): corneum, lucidum (only in palms of hands and bottoms of feet), granulosum, spinosum, basale.Innovative Injection Use Research Paper
Dermis: The dermis is the layer of skin below the epidermis and it consists of connective tissue and protects the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane.
It also harbors many mechanoreceptors (nerve endings) that provide the sense of touch and heat. It consists of the hair follicles, sweat glands, sebaceous glands, apocrine glands, lymphatic vessels and blood vessels. The blood vessels in the dermis supply nourishment and waste removal not only from its own cells but also from the stratum basale of the epidermis.
Hypodermics: It is not the part of the skin, and lies below the dermis. Its function is not only to put together the skin and the underlying bone and muscle but also supplying it with blood vessels and nerves. It mainly consists of loose connective tissue and elastin.
It consists of main cell types such as fibroblasts, macrophages and adipocytes (the hypodermis contains 50% of body fat). Fat mainly acts as padding and insulation to the body.
NEEDLE FREE TECHNOLOGY: ORIGIN AND METHODOLOGY
Needle free technology (Jet injectors), were developed in the 1930s and used widely over 50 years in mass vaccination programs in patients suffering from smallpox, polio, and measles. Mechanical compression is used to force (generated by a compressed gas typically air, CO2 or nitrogen) fluid through a small orifice, these devices created a high pressure stream that could easily penetrate the skin, subcutaneous tissue and underlying shallow muscle in order to deliver the vaccine in a fraction of a second. One major problem to needle free injections has been the wetness related with residual vaccine on the skin surface that may cause the vaccine administrator to think that the vaccine was not properly administered. Needle free injection technology has been designed to deliver antibiotics, iron dextran or vaccines comfortably, accurately, easily and rapidly without the application of a needle. Needle free injection is precise, reliable, and virtually the same every time. There are 3 stages in needle free delivery: Stage 1, the peak pressure phase, in which optimal pressure is used to penetrate the skin (< 0.025 sec); Stage 2, the delivery or dispersion phase (~ 0.2 sec); and Stage 3, the drop-off phase (< 0.05 sec). This pressure profile is steady with each administration of vaccine which ensures that each animal is vaccinated at the proper tissue depth. The needle free injection technology enhances the dispersion of medication throughout the tissue. As the fluid stream forces its way through the tissue, a path of least resistance is followed, resulting in a broadly dispersed, and spider web like distribution of the medication.
Types of Needle Free Injection Systems:
Needle free technologies are of three types:
1. Powder injections
2. Liquid injections
3. Depot or projectile injection.
1. Powder Injections
For delivery via skin, the particles must only pierce the outermost barrier, the stratum corneum. So, drugs delivered with powder injection technology or Needle Free Injection (NFI) reach the circulatory system faster than those administered by subcutaneous injection, because it is an intradermal delivery and the capillary blood supply is immediately nearby to the site of administration.
The powder injection system for particle delivery is the combination of a device with a specially formulated powdered drug. Exclusive devices have been configured for injection into any physically accessible tissue, normal skin or mucosal sites. Some systems have been designed for single use and are entirely disposable and others, intended for longer courses of therapy, have some reusable elements. For convenience and economy, reusable systems have only the drug and pressurized helium energy source in a single cartridge that is replaced for each injection.Innovative Injection Use Research Paper
The principle of all the devices is the same; i.e. the harnessing of the energy of a transient gas jet to accelerate a premeasured dose of particulate drug formulation. The most common orifice size is 0.127mm, compared to a 25 gauge needle, which is about 1mm. So, process is completely painless.
The powder injection systems are powered by a manufactured helium gas aluminum microcylider of ampoule design and make use of a drug cassette or package to introduce the powder into the gas flow. In operation, the microcylider tip can be broken when the device is pressed against the tissue site that is to be treated. This releases the compressed helium suddenly to open the drug cassette for delivery of its payload to the tissue. The gas does not actually penetrate the skin, instead, it is reflected back in to the device through a silencer. The silencer is essential because the flow is rapidly supersonic. The other components of the device are manufactured from medical grade plastics using standard injection molding techniques.
Ideal characteristics of powder particles
Powder is an essential component of the powderject technology. For powder injections, particle quality and size distribution are individually essential, not only traditional shelf life chemical stability but also physical stability is required. The powder must retain its size distribution during transport and storage and particles must be sufficiently robust to withstand the highly energetic gas jet within the device as well as ballistic impact with the skin. The dispersed particles must then dissolve and the payload diffuses to act locally or transported by the systemic circulation to the desired site of action in the body.
The particles also must be strong because they hit the skin at high velocities. The particles have been clocked as fast as 900 meters per second, with 400 to 600 meters per second being the more typical range. For powders having particle densities around 1g/cc, mean diameters of greater than about 20 μm are required for skin penetration for typical velocities. For particle size ranges above 100 μm, local skin tolerability limits the delivery.Innovative Injection Use Research Paper
In the powder injection system, process to make powder particles is powder compression, milling and sieving. Other more readily scalable methods include spray drying, spray freeze drying, fluid bed drying, spray coating of seed particles, solution filling and drying preformed hydrogel beads and emulsion techniques to form erodible micro particles.
By using the drug in powder form rather than dissolved in liquid, a much smaller volume of material is shot through the skin, so the injection becomes painless. Bio erodible carriers, slowly dissolving excipients or specific, less soluble salts or dissolution aids can provide sustained release or otherwise altered pharmacokinetics to improve drug performance. Protein drugs are very potent so it fits powderject systems perfectly.
2. Liquid injections
The basic principle of this injection is, if a high enough pressure is generated by a fluid in intimate contact with the skin, then the liquid will punch a hole into the skin and will be delivered into the tissues in and under the skin. Although the same principle is applied as in powder, there is difference in the actual design and operation of the powder injection devices.
3. Depot injections
Depot injections are given in the muscle, where they create a depot of a drug that is released continuously over a specified period of time.
DESIGN
The air forced needle free injection systems are usually made up of three components which include an injection device, a disposable needle free syringe and an air cartridge. The injection device is fabricated of a durable plastic. It is designed such that it is easy to hold for self administration of medicine. The needle free syringe is also fabricated of plastic. It must be sterilized and is the only piece of the device that must touch the skin. The syringe is made such that, it should be disposed after every use.
RAW MATERIALS
Since these devices directly come in contact with the body, they must be fabricated from materials that are pharmacologic ally inert. The materials also must be capable to endure high temperatures since they are heat sterilized. Air forced injection systems are available in different shapes and sizes. The external shell of the device is made from a high strength, lightweight thermoplastic such as poly carbonate. Poly carbonates are polymers that are formed synthetically through various chemical reactions. To make the polymer significant to mold, fillers are added. These fillers help to make plastics more durable, lightweight, and rigid. Colorants are also included into the plastic to modify the overall appearance.Innovative Injection Use Research Paper
THE MANUFACTURING PROCESS
There are various methods of producing needle free injection system. These systems are made through a step by step process which involves molding the pieces, assembling them, decorating and labeling the final product. The individual pieces are usually produced off site and arranged by the needle free injection system manufacturer. All of the manufacturing process is done under sterile conditions to avoid the spread of disease.
Making the pieces
a) The first step consists of production of the component plastic pieces from plastic pellets. This is done by injection molding process. Plastic pellets are put into large holding bin on an injection molding machine. They are then heated to make them flow able.
b) The above material is then passed through a hydraulically controlled screw. As the screw rotates, the plastic is directed all the way through a nozzle which then injects it into a mold. The mold is fabricated of two metal halves that form the shape of the part when brought together. When the plastic is in the mold, it is held under pressure for a specified period of time and then allowed to cool. The plastic inside hardens due to cooling.
c) As the mold pieces are separated, the plastic part falls out on top of a conveyor. The mold closes again and the process is repeated. After the plastic parts are driven out from the mold, they are physically inspected to make sure that any kind of damaged parts are not used.Innovative Injection Use Research Paper