Needle free Injection-main project(7th sem)


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Needle free Injection-main project(7th sem)

  2. 2. 2CERTIFICATECertified that the seminar work entitled STUDY OF NEEDLE FREE INJECTION is a bonafidework carried out byKAUSHIK BANDOPADHYAY ROLL NO.08109031014In partial fulfillment for the award for degree of BACHELOR OF TECHNOLOGY in BIO-MEDICAL ENGINEERING of the WEST BENGAL UNIVERSITY OF TECHNOLOGY,KOLKATA during the year 2011-2012. It is certified that all corrections/suggestions indicatedfor Internal Assessment has been incorporated in the report deposited in the Department. Theseminar report has been approved as it satisfies the academic requirements in respect of seminarWork prescribed for Bachelor of Technology Degree.…………………………….. ………………………………………..MR. SUJAN KRISHNA SAMANTA DR. SUKUMAR ROYSeminar Coordinator HOD, BME, NSECName of the Student: KAUSHIK BANDOPADHYAYUniversity Roll No.: 08109031014Name of Examiners Signature with Date1.2.3.
  3. 3. 3ACKNOWLEDGEMENTI am greatly indebted to our seminar Guide Dr. Sukumar Roy, Department of BiomedicalEngineering, for providing us all possible help and support while doing this work. Without hisguidance the work would not get such a progress.I am highly obliged to our co-guide Mr. Sujan Krishna Samanta, Assistant Professor, Departmentof Biomedical Engineering for his timely help and guidance. We are also thankful to him for hisvaluable lectures that he offered to us during project.I am also thankful to Ms. Sumana Chatterjee, Lecturer Dept. of BME, for her activecooperation.I extend my thanks giving to all respected Faculty Members and our friends directly or indirectlyassociated with my work, who contributed their personal level best which enabled me for asuccessful completion of this seminar.Signature:
  4. 4. 4CONTENTSChapter No. Chapter Page No.I Introduction 6II Relevance of this technology in today’s world 7III Classifications of Needle Free Injections 8IV Advantages of using Needle Free Injection Technology 14V Raw materials used for manufacturing Needle free Injection 17VI Manufacturing Process 17VII Quality Control and Management 18VIII Popular Brands present Internationally. 19IX Limitations of this Technology 21X Conclusion 22XI References 23
  5. 5. 5LIST OF FIGURESChapter No. Fig No. Description Page No.III 1.1 Nano-Patch 91.2 Application of Nano-Patch on skin surface 101.3 Operation Mechanism of Nano-Patch 111.4 Jet Pressured Needle Free Injection 121.5 Operation Mechanism of Jet Pressured 13Needle free Injection
  6. 6. 6INTRODUCTIONAs long as drugs have been known to cure diseases, people have searched for better methods ofdelivering them. During the early nineteenth century researchers made a series of discoveries thateventually led to the development of the hypodermic needle by Alexander Wood in 1853. Thisdevice was used to give morphine to patients suffering from sleeping disorders. In subsequentyears, the hypodermic needle underwent significant changes which made them more efficient touse, safer, and more reliable.As technology advanced, procedures for delivering drugs metamorphosed. Today it has reacheda stage where conventional drug delivery using needles might become history. Thanks to theinvention of “Needle Free Injection Technology” which brings in a plethora of advantages,enough to set conventional injections in the pages of history. Definitely a relief for millions asthis technology promises no pain, which is more than a psychological disease which sets manyat unease, even hyper reactive, irrespective of age, gender, geography. But it is not merely thepain-less factor that for this technology has been conceived, deeper aspects such as effective andefficient delivery of drugs, extensive inoculation during pandemics, cost effectiveness and manymore important objectives are behind which have led to formulation of this latest technology inmedical science. Such aspects will be extensively discussed as one surfs across the pages of thisproject leading to enlightenment and relevance of this technology at this present moment and thenear future. Happy reading and discovery!
  7. 7. 7RELEVANCE OF THIS TECHNOLOGY IN TODAY’S WORLD.People are given injections to protect them from influenza, tetanus, cholera, typhoid, andother diseases. When a needle is inserted through the skin, the vaccine (or drug) it carriesprovides systemic immunity. This is because the vaccine gets into the bloodstream and provokesthe body to create antibodies that are carried throughout the entire body.In many countries, children may get over 13 vaccine injections by the age of 16.Unfortunately, there are a variety of problems associated with the hypodermic needles used forthese 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 reusability. If a needle syringe is notsterilized, reusing it can lead to the spread of disease. Additionally, many people have a fear ofneedles which causes them to avoid treatment. These drawbacks have led to the development ofalternative delivery systems to needle injections.Needle-free systems are designed to solve these problems making them safer, lessexpensive, and more convenient. It is anticipated that these systems will increase the incidence ofvaccination and reduce the amount of prescribed antibiotics. Moreover, they should reduce thenumber of needle stick accidents that have resulted in some health care workers contractingdiseases.
  8. 8. 8CLASSIFICATION OF NEEDLE FREE INJECTIONSNeedle free Injections can be classified into two types based on their mechanism of drugdelivery, namely: 1) Nano-patch, 2) Jet pressure Needle free Injection. The mechanism of theiroperation will be described in details as every classification is introduced.1) Nano-Patch:This is the latest form of needle free drug delivery system where a patch containingmedicine called “Nano-Patch” is used. This drug delivery system is mainly used forvaccination purpose, though delivery of routine medications are also performed. Nano-patch isa specially designed surface having approximately 20,000 micro-projections per squarecentimeter. The size of the patch is about the size of a stamp used in postal services. The basemembrane and the micro-projections are made up of some fine polymeric material like LDPE(Low Density Poly-Ethylene) and the micro-projections hold the drug in extream minutevolume. Due to the presence of a high number of micro-projections a sufficient volume of drugis delivered.A team of 20 researchers led by Professor Mark Kendall, from the Australian Institute forBioengineering and Nanotechnology at The University of Queensland developed this Nano-Patch. Intercell USA was the first medical organization to produce such needle less drug deliverysystem with the help from the global design giant Ideo, USA.Nano-Patch involves transcutaneous delivery of drugs, i.e delivery of drugs just beneaththe skin surface. It delivers the drug directly into the transcutaneous layer which is rich inimmune cells. And unlike the needle and syringe, which places the drug into the muscle havingfar more less number of immune cells. As production of antibodies is directly proportional to theamount of antigens the immune cells are exposed to, the Nano-Patch techniques scores far betterthan the conventional Needle inoculations.
  9. 9. 9Fig 1.1Methods of Application:Drug delivery through Nano-Patch can be classified into two categories, namely 1) Sand-paperaided delivery , 2) Iontophoresis enabled delivery.1) Sand-paper aided delivery:This is one of the methods of application of Nano-Patch before the patch is placed on thesurface of the skin. Scientists have developed a special type of sandpaper which can be placedover the skin surface prior to the application of Nano-Patch. By pressing it onto the skin andpulling it in a motion akin to removal of a tape from a package helps in removing a skin layerof 25 microns thickness, just sufficient for the micro-projections of the patch to deliver thedrug at the immune cells’ layer. This is an extremely simple method and does not requiremedical supervision or expertise for administration of the drug. Moreover, there is noperception of pain when the sand paper is stripped off or when the Nano-Patch with itsmicroscopic projections are pressed onto the skin. The scratch indented by the sand paper is
  10. 10. 10invisible and to aid the proper positioning of Nano-Patch an ink mark is left behind by the sandpaper. Thus making the technology absolutely user friendly.Fig 1.2This diagram shows the entire procedure of application of the Nano-Patch. Figure1 shows theNano-Patch kit containing the Nano-Patch and the specially devised sand paper.Figure2 shows how the entire set up is to be applied on the skin surface and then the sand paperis to be pulled.Figure3 shows that after the sandpaper is pulled off, the Nano-Patch can be applied.2) Iontophoresis enabled delivery:This is another type of application of Nano-Patch. In this method there is no need toremove a thin layer of skin surface, rather the patch is directly applied on the skin surface and aextremely small amount of electric discharge( a few microvolts) is applied over the patch todrive the drug molecules into the skin surface. This method is less popular because it requires aexternal device, i.e a driving electrode to push the micro sized drug molecules which arepresent only in hospitals. This technique also demands medical supervision and expertise forproper application of the electrical discharge.
  11. 11. 11Mechanism of Operation:Fig 1.3The nano-projections containing the drug( in case of normal treatment) or antigen( incase of immunization) puncture the skin surface and delivers the drug/antigen into theepidermis. The epidermis is rich of Langerhans cells, members of the immune system. Theirrole is to pick up the antigens and physically move from epidermis to the nearest Lymph node.Lymph nodes the hub of our immune system. Once there, Langerhans cells mature and displaythe antigen to the passing naïve T-cells.T-cells are specialised cells which specifically recognise one type of antigen. It’s like apoliceman with a picture of just one criminal. A naïve T-cell doesn’t have a picture yet. Itcollects one from a Langerhans cell and other cells in the lymph nodes. With that the T-cellmatures, looking out for the antigen. Next time it sees it, it will be armed and ready.T-cells, along with B-cells, protect you from getting the same disease twice. T-cells inparticular are needed to clear infections like HIV and malaria, and needle vaccines don’tstimulate them enough. The nano-patch focuses on T-cells specifically. It gives them their firstlook at the disease, without the pesky side-effect of getting traumatically ill.
  12. 12. 122) Jet Pressured Needle Free Injection:A UK based company, The Medical House (TMH) in collaboration with Bioject, a USAbased company developed the Jet pressured Needle free Injection in the year 2001. This devicewas developed specifically for injecting Insulin and Human Growth hormone. Though these twocompanies had collaborated, they fell apart a few years after signing the pact and each of themlater came up with revolutionary products: Vitajet , by Bioject and SQ-Pen by TMH. Both thesedevices have been extremely popular since their inception due to the fact that patientsadministered drugs without the depressing sight and pain of needle and their ease of use withoutany medical supervision or expertise.Variations of the above mentioned devices have been developed to make the technologymore user friendly and available at a cheaper cost so as to improve the life of millions sufferingfrom diabetes, the silent killer or malfunction of growth hormone. International Drug control andRegulatory organizations such as NHS Drug Tariff, COP( Comfort Optimization Programme)have their control over such devices and the companies manufacturing them obeys suchguidelines to manufacture safe and economically viable products.Fig 1.4
  13. 13. 13Mechanism of Operation:Needle-free injectors use jet pressure to inject the drug rapidly into the tissue at the correctdepth. The jet is achieved by forcing the drug through a specially designed nozzle, which iscompleted in only 300 milliseconds. The drug delivery involved is Transcutaneous type as thejet penetrates the tissue depositing the drug in the subcutaneous layer.The air-forced needle-free injection systems are typically made up of three componentsincluding an injection device, a disposable needle free syringe and an air cartridge. Theinjection device is made of a durable plastic. It is designed to be easy to hold for self-administration of medicine. The needle-free syringe is also plastic. It is sterilized and is theonly piece of the device that must touch the skin. The syringe is made to be disposed afterevery use and pressurized metal air cartridges are included. Some devices have air hook-upsthat attach to larger containers of compressed air. Some air-forced systems use a re-usablespring to generate the pushing force instead of pressurized air cartridges.Fig 1.5The diagram above shows the mechanism of drug delivery of a Needle and a Jet pressuredNeedle Free Injection. Diagram on the left shows the needle based delivery where there is adistinct puncture of the skin surface and the drug after delivery gets trapped for a while withoutbeing diffused immediately. On the other hand, there is no puncture when the Jet PressuredNeedle free Injection is used , due to the specially developed nozzle the drug penetrates through
  14. 14. 14a skin pore and is immediately dispersed into the epidermis, thus enabling a faster transport tothe body.ADVANTAGES OF USING NEEDLE FREE INJECTION TECHNOLOGYAdvantages galore as one delves into the Neddle Free Injection Technology. The biggest proofof its credibility and effectivity is its acceptance among the patients and wide practice by medicalprofessionals and organizations. Though this is a pretty new concept in India, but in developednations this technology is in vogue. A comprehensive and exhaustive list of advantages of thistechnology is listed below:1) Painless ProcedureThe word “Needle free” itself psychologically suggests a painless procedure andcertainly it does live up to its name and intriguing nature. Be it Nano-Patch or Jet Pressure orGas Powered Needle free Injection all of these provide pain less inoculation of drugs into thebody. Thus, causing a relief to millions, irrespective of age, gender or geography who areneedle-phobic.2) Relief to patients who have to be administered with Transdermal Inoculation many timesa dayThese are mainly people suffering from acute Diabetes. Such patients have to beadministered with insulin at regular intervals to keep a check on their blood sugar levels. Thisis an extreme painful procedure as the patient has to undergo numerous injection pierces aday and for the entire duration of his/her stay in the hospital. Needle free InjectionTechnology thus comes as a blessing to such people.3) Efficient use of VaccineResearchers have found that the amount of drug that is introduced inside our bodythrough conventional injections do not cause the right magnitude of effect which actually thatamount of drug should do. This means that a considerable amount of drugs do get wasted. Asevident from above diagrams some portion of the drugs do get trapped inside the muscles and
  15. 15. 15are eventually excreated from our body. Such a thing never occurs in Needle free injections.A specific amount of drug is administered which gets totally used by our body as there is noentrapment and immediate dispersion upon introduction.4) Pandemic effectiveDuring pandemics such as Cholera, diarrhea, dysentery availability of drugs and medicalprofessionals are not in abundance which leads to incomplete administration of drugs amongthe patients thus leading to death of many. Such a mishap can be easily averted if a massamount of such Needle free Injections can be delivered to families where they themselvescan administered under minimum medical supervision.5) Self administrable:As previously mentioned, needle free injections can be administered without any medicalsupervision or expertise, there is no need for patients to visits clinics or hospitals.6) Less expensive:In developed nations the cost of Needle free injections are less than conventional needleinjections. Though this is not a reality is developing countries, efforts are being made torealize such a project.7) Zero Contamination:This is due to the fact that the needle free injections are for one time use only. Even ifone tries to reuse it( as it happens in case of conventional injections) one can’t because thedrug cannot be refilled into the device. Thus making the device absolutely fool proof fromsabotage by unscrupulous agents, thereby rendering cent percent safety and contaminationfree inoculation.
  16. 16. 168) Better drug diffusion:Conventional injections deliver drugs into our muscles where it gets trapped for a periodof time before getting diffused into our body, thereby causing a delay in action of the drug.Moreover there is also a possibility of the drug being trapped inside the muscles thusresulting in wastage of the drug. Such things never happen in Needle free injections becausedrugs are instantaneously transported into our system, thanks to the Langerhans cells andLymph nodes in our body which supports such a brilliant mechanism.9) Zero disposal Hazard:Conventional needle injections have mainly two types of disposal hazards. Firstly, injurycaused to the the person handling the sharps which mioght lead to devastating effects ascontamination is inevitable. Secondly there is a fear of reusability of the used sharps. Thoughthe second factor has been stopped but still unscrupulous activities thrives where used needleinjections are washed, rinsed packed and again sold into the market. Such possibilities wouldnever occur if needle free injections are used.10) Ideal for Developing countries:This is the one of the most propelling motives which has culminated in design of thistechnology. Developing countries have a huge population but lacks proper medical facilitiesand scarcity of trained medical personnel. Thus during any vaccination drive or treatmentduring pandemics most of the mass are left untreated, thereby causing permanent impairmentor even death. To eradicate such an undesirable happening this technology gives the bestpossible solution.
  17. 17. 17RAW MATERIALS USED FOR MANUFACTURING NEEDLE FREE INJECTIONSSince these devices directly contact the body, they must be made from materials that arepharmacologically inert. The materials also must be able to withstand high temperatures becausethey are heat-sterilized. Jet pressured injection systems are available in different shapes as sizes.The outer shell of the device is made from a high strength, lightweight thermoplastic such aspolycarbonate. Polycarbonates are polymers produced synthetically through various chemicalreactions. To make the polymer easier to mold, fillers are added. These fillers make plastics moredurable, lightweight, and rigid. Colorants are also incorporated into the plastic to modify theappearance. Prior to manufacture, the plastics are typically supplied in pellet form with thecolorants and fillers already incorporated. Jet pressured systems typically use carbon dioxide orhelium gas to propel the medicine into the body.MANUFACTURING PROCESSThere are numerous methods of producing each needle-free injection system. The followingprocess focuses on the production of an air-forced system. These systems are made through astep by step procedure which involves molding the pieces, assembling them, and decorating andlabeling the final product. The individual pieces are typically produced off-site and assembled bythe needle free injection system manufacturer. All of the manufacturing is done under sterileconditions to prevent the spread of disease.Making the pieces1) The first step requires the production of the component plastic pieces from plastic pellets.This is done by a process called injection molding. Pellets of plastic are put into a large holdingbin on an injection molding machine. They are heated to make them flowable.2 ) The material is then passed through a hydraulically controlled screw. As the screw rotates, theplastic is directed through a nozzle which then injects it into a mold. The mold is made up of twometal halves that form the shape of the part when brought together. When the plastic is in themold, it is held under pressure for a specified amount of time and then allowed to cool. As itcools, the plastic inside hardens.
  18. 18. 183) The mold pieces are separated and the plastic part falls out onto a conveyor. The mold thencloses again and the process is repeated. After the plastic parts are ejected from the mold, theyare manually inspected to ensure that no significantly damaged parts are used.Assembling and labelingThe parts are next transported to an assembly line. In this production phase variousevents occur. Machines apply markings that show dose levels and force measurements. Thesemachines are specially calibrated so each printing is made precisely. Depending on thecomplexity of the device, human workers or machines may assemble the devices. This involvesinserting the various pieces into the main housing and attaching any buttons.PackagingAfter the assembly step, the injection devices are put into packaging. They are firstwrapped in sterile films and then put into cardboard or plastic boxes. Each part is packaged somovement is minimal to prevent damage. For consumer products, an instruction manual isincluded along with safety information. These boxes are then stacked on pallets and shipped viatruck to distributors.QUALITY CONTROL AND MANAGEMENTQuality control checks are done throughout the manufacturing process. Line inspectorscheck the plastic components to assure they conform to predetermined specifications. Visualinspections are the first test method, but measuring equipment is also used to check thedimensions including size and thickness. Instruments that can be used include laser micrometers,calipers and microscopes. Inspectors also check to make sure the printing and labeling is correctand that all the parts are included in the final packages.Since these devices can have various safety issues, their production is strictly controlledby the Food and Drug Administration (FDA). Each manufacturer must conform to variousproduction standards and specifications. Announced and unannounced inspections may occur toensure that these companies are following good manufacturing practices. For this reason detailedrecords must be kept related to production and design.
  19. 19. 19POPULAR BRANDS PRESENT INTERNATIONALLYBiojectorr 2000The Biojector 2000 is a durable, professional-grade injection system designed forhealthcare providers. The Biojector 2000 is the only needle-free system in the world cleared bythe FDA to deliver intramuscular injections. The system can also deliver subcutaneousinjections, and is being used for intradermal injections in clinical trials.The Biojector 2000 uses sterile, single-use syringes for individual injections, whichprevent the cross-contamination that has been reported with fixed-nozzle jet injection systems.More than 10 million injections have been administered successfully using the Biojector 2000,with no reports of major complications. Because there is no needle, the Biojector provideshealthcare workers with an unparalleled level of protection against accidental needlestickinjuries. In high-risk situations, such as delivering injections to patients known to be infectedwith HIV or hepatitis, the Biojector is an ideal injection system.Vitajet 3The Vitajet 3 is an easy-to-use, economical needle-free injection system for deliveringinsulin. The system requires no maintenance or re-assembly. With disposable nozzles that arereplaced once-a-week, the Vitajet 3 offers the quality of a reusable medical product, with theconvenience and safety of a sterile disposable. The exclusive, easy-to-read Crystal Checkdisposable transparent nozzle allows to inspect the dosage prior to injection and visually confirmloading and full discharge of your insulin after each use.The Vitajet 3 received the FDA marketing clearance for delivering subcutaneousinjections of insulin in 1996. Since then, the system has been used to deliver hundreds ofthousands of injections, safely, economically, and without the use of a needle.Cool clickBioject developed the needle-free injection system for delivering Saizenrecombinant human growth hormone. In some children, naturally occurring growth hormone is
  20. 20. 20absent or is produced in inadequate amounts. In these cases, Saizen or growth hormonereplacement must be injected to maintain normal is a customised version of Bioject’s Vitajet 3 needle-free injection system. Thesystem includes customized dosage features to accurately deliver variable doses of Saizen andwas designed with bright colors to make the injector attractive and non-threatening to children.The received FDA market clearance for delivering subcutaneous injections of Saizenin June, 2000.SeroJetThe SeroJet is a needle-free injection system for delivering Serostim recombinant humangrowth hormone for treatment of HIV-associated wasting in adults. HIV-associated wasting is ametabolic condition in which people infected with HIV lose body weight. If not treated, thiscould result in increased morbidity and mortality.Serono developed Serostim to treat this condition by utilizing the natural properties ofgrowth hormone in increasing lean body mass. SeroJet is a customised version of Bioject’sVitajet needle-free injection system. The system includes customised dosage features toaccurately deliver variable doses of Serostim. The SeroJet received FDA market clearance fordelivering subcutaneous injections of Serostim in March 2001.IjectBioject has developed a second-generation gas-powered injector known as the Iject,which is based on the design and performance of the B2000 and is intended to serve as a single-use pre-filled device. The pressure profile of the Iject has been documented by in vitro testing tobe virtually the same as that of the B2000, and injection performance of the two devices istherefore predicted to be equivalent.The Iject is a pre-filled single-use disposable injection device configured to administer0.5 to 1.00 ml subcutaneous or intramuscular injections. The device is distributed “ready to use.”Thus, it requires no additional parts or modifications for function.The device is primed by rotating the trigger sleeve 180 degrees, and an injection is administeredby advancing the trigger sleeve while the nozzle is held against the injection site. The Ijectneedle-free injection system is an investigational device, subject to the US Food and DrugAdministration clearance for commercial distribution.
  21. 21. 21Biovalve’s Mini-Ject technologyThe Mini-Ject represents the next generation in needle-free injection systems bycombining the features of accuracy reliability, a variety of pre-filled options, comfortableadministration, and full disposability, all within a patient friendly easy-to-use design. The Mini-Ject can deliver a wide range of drugs, ranging from small molecules to large proteins, fragileantibodies, and vaccines. Delivery can be targeted to intradermal, subcutaneous or intramusculardepending on the clinical need. No other single-use needle-free delivery technology provides thesame level of performance as the Mini-Ject technology with the ability to target specific tissuelayers over such a broad range of drug volumes (0.1 mL to 1.3 mL) and viscosities.Antares’ Medi-Jector Vision technologyAntares Pharma, one of the pioneers in the field of needle-free injection technology hasdeveloped Medi-Jector Vision technology which is used to deliver insulin to diabetes sufferers. Itis a newest marketed version of the reusable, variable dose, spring-powered device for insulindelivery. This technology is also being used to deliver human growth hormone. Its plastic,disposable needle-free syringe allows the patient to see the dose prior to injection. It is marketedin US and Europe for insulin administration since 1999.LIMITATIONS OF THIS TECHNOLOGYLike all technologies this technology too has its share of drawbacks. Though it is not aplenty butone major drawback which is a clinical concern is that the high pressure delivery of drugs by theJet pressured needle free Injection can damage fragile molecules beneath our skin surface,especially Monoclonal antibodies. This can be resolved if a specialized device is employed tocontrol the exact pressure of drug delivery. Though this problem is faced only by patients whoundergo multiple inoculations within a short period of time thus is not of a major concern for thegenerally ill patients or patients for vaccination.
  22. 22. 22CONCLUSIONAfter delving into the depths of this technology and getting enlightened by the magnitude of itsacceptance and value one might ask: Is the future needle-free? The answer for developedcountries is a big Yes but for developing countries it is still questionable, though this technologyis designed appropriately for such nations. The reason for such an occurrence being technologyintroduction in a country doesn’t solely depend on the prowess of the technology. Commercialconsiderations, impediments from local business giants and various other factors are to be met.Still there appears to be tremendous opportunity for needle-free technology to have major impactin the industry. Although organizations such as WHO( World Health Organization) and CDC(Centre for Disease Control) and groups like Gates Foundation have supported the developmentof needle-free alternatives for drug delivery, it is likely that dramatic change may occur onlywhen a large pharmaceutical or biotechnology company adopts needle-free technology anddemonstrates its versatility, acceptance and value in major therapeutic area.
  23. 23. 23REFERENCESWebsites:1) www.bioject.com2) www.glidepharmaceuticals.com3) Google4) Google Scholar