Needle Free Injection Systems

Sree Datta Institute of Pharmacy 1

Needle Free Injection Systems

Prepared by Satish kumar K Guided by Ramakrishna Department of Industrial

Pharmacy

17 Feb 2011


Contents

1. Introduction And History

2. Structure of Human Skin

3. The Injection Process: a Qualitative Description

4. Biomechanical Properties of Human Skin

5. Model Test Systems for Liquid Injectors

6. Advantages

7. Conclusion and References

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Introduction

To overcome the problems related to needle based injections, there is one technology that has received constable attention during the past few years and that all of the sought after benefits is – Needle Free Injection Technology (NFIT) discovered in 19th century in France

Needle free technology offers the very obvious benefit of reducing patient concern about the use of needle

The main goal of this NFIT is to reduce patient phobia towards needle injection

This is mainly useful for the patients who are suffering from chronic diseases who require injectable products 2 or 3 times a day. For example : Diabetes patients

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Needle Free History

In use since 1947– Military– International Public Health Campaigns

Widely used for mass immunizations and disease eradication.– Smallpox (1975)– Polio (when injected)– Measles (Brazil; 1990 to 1996)

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Needle Free Requirements for the Developing World

Safety– Pathogen Transfer Issues– Disposal of Bio-Hazardous Material

Speed– High Thru-put

Ease of Use– Minimize training – Reduce repetitive motion injuries for health care workers– Simplify maintenance and spares logistics

Energy– Should be capable of being self powered

Cost– Must be comparable or less than traditional needle and

syringe on a per injection basis

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Whole Skin Structure

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The Epidermis I: Differentiating Keratinocytes

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stratum corneum corneocytes + lipid

stratum lucidum thin layer

stratum granulosum produces lipids

stratum spinosum numerous layers

start of differentiation stratum basale one layer cell division


The Epidermis IIThe skin‘s diffusional barrier

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The skin‘s diffusional barrier


Cells of the Dermis

Fibroblasts: produce fibres and ground substanceMast cells: around vessels = allergic responseMacrophages: phagacytosis

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Fibres of the Dermis

The dermis‘ mechanical property

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The Hypodermis (Subcutaneous Layer)

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Description

The pharmacuetical sub assembly includes

Glass tube Pistons Nozzle made of standard materials Can be easily filled in on conventional filling lines

Recently Glide Pharma introduced a new model of needle free injection

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Sree Datta Institute of Pharmacy 1317 Feb 2011


Mechanism

Needle free injection technology works by forcing liquid medication at high speed through a tiny orifice that is held against the skin

This creates an ultra stream of high pressure fluid that penetrates the skin without the use of needle

The design of this device has a majot influence on the accuracy of subcutaneous delivery and the stress imposed on the product to be delivered.

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The design must ensure that a sufficiently high pressure is generated to puncture the skin, while the subsequent pressure is reduced to ensure that the molecule is deposited comfortably at a level that does not reach the muscle tissue

High pressure delivery could potentially fragile molecules, such as monoclonal antibodies.

Successful delivery of such molecules, therfore, requires a device with carefully controleed power nuances.

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The Injection Process: a Qualitative Description

(Needle & Needle-Free)

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Comparison with Percutaneous Absorption

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Dissolved Drug

Diffusion

Partition: 21 kcc

Diffusion/Partitioning ProcessMajor diffusional barrier is stratum corneum

- morphology gives altered A* and l*- L lipid structure


Needle/Needle-Free Injection

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NF- liquid

NF- powder

Needle

- Tissue penetration via needle or substance (fluid/particles) projected from needle-free device- puncture (mechanical failure) of epidermis & dermis- deformation of dermis/hypodermis


Needle Free Technology

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How does It works?

Medication is driven at high speed

through a tiny orifice A fine stream of medication penetrates

the tissue Injection event requires less

than 0.5 seconds Injections can be IM, SC or ID


Needle free dispersion patterns(Intra – Muscular)

Spherical bolus Amplified Dispersion

- Lowest possible - Very high

SA/V ratio SA/V ratio

- Limited tissue - Enhanced tissue

disruption disruption

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Needle Free Technology What problems does it solve

- Avoids needle stick hazard

- No sharps disposal problems

- Eliminates the concern for the re-use of needles

- Injection pain is reduced in most cases

- Speeds the injection cycle

- Improved bio-availability of vaccines

- Reduces the system cost of injection

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The Injection Process Viewed Qualitatively

Puncture & deformation of skin tissue is complex issue !

Requires knowledge of biomechanical properties ofskin tissue

Problem: biomechanical behaviour of skin isinhomogeneous, non-linear (depends on stress rate)& anisotropic

Skin layers (SC, E & D) have different biomechanical properties

- SC : high tensile strength, but thin - E/D: elastic & viscous behaviour (collagen & elastin

fibres, ground substance)

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Needle-Free Injection Systems

Part 3: Biomechanical Properties of Human Skin

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Biomechanical Properties of Skin:Measurement Techniques

How to measure biomechanical properties of humna skin?- Various experimental setups possible:

1. Stretching measurements in vitro & in vivo- stress versus strain

2. Compression measurements

3. Fracture resistance

4. Ultrasonic measurements

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Biomechanical Properties of Skin:1. Stretching Experiments with Skin

Non-linearly elastic over whole stress range until yield

- stress-strain curve non-linear = elastin & collagen fibres

- large deformations before yield: ≥ 40 %

- highly viscoelastic (time dependent)

- anisotropic

- behaviour comes from dermis

- varies with age, sex, stress state, etc

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Biomechanical Properties of Skin:2. Compression Experiments

Can apply up to 70 N force to skinMaximum deformation of 30 mm

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Biomechanical Properties of Skin:3. Fracture Resistance Experiments

FR = energy required to separate a tissue sheet into 2 pieces [J/m2]

Interfacial fracture energy = f(work of adhesion, viscoelastic energy dissipation)

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Biomechanical Properties of Skin:4. Ultrasonic Elasticity Measurement

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Summary of Biomechanical Properties of Skin

Unique morphology defines the skin‘s mechanical properties

Stress/strain behaviour determined by dermis:

- linearly elastic over large low stress range E = 5 – 100 kPa

- similar compressibility as rubber = 0.49

- tensile strength very high above elastic limit (collagen)

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Needle-Free Injection Systems

Part 6: Model Test Systems for Liquid Injectors

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Needle-Free Injection of Liquid Epidermis Dermis Hypodermis

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High pressure liquid jet emerges from nozzle - 150 – 200 mm , - velocity 100 m/s - static pressure 10 MPa on skin surface®Liquid jet punctures skin tissues - forces related to needle penetration force®Liquid jet disperses in dermis(D) & hypodermis (HD) - force sufficient to overcome Young‘s modulus of D/HD (10 – 100 kPa) - dose volume small = assumption of linear elasticity


Technologies

Mhi-500: Mhi-500 is a needle free insulin delivery system which

offers a a great benefit in diabetics care

Mhi-500 injects insulin by using a fine, high pressure jet of insulin.

This jet then penetrates the tissue, depositing the insulin In the subcutaneous layer.

This jet is created by forcing the insulin through a precisely designed nozzle that is held in contact with the tissue during the injection.

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Recojet

Recojet is India’s first needle free insulin device and poised to revoultionize the insulin therapy

This is needle free insulin device mainly launched for injecting Recoinsulin (Recombinant human insulin).

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Biojectwww.bioject.com

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pharmaject

Cool click

bio2000


Bioject

Biojector 2000

Designed for the professional healthcare market

- Immunization programs

- Hospitals

- Clinics

Self InjectorsSpring powered

CO2 powered with electronics

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Biojector injection capabilities

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Other well known manufacturers are :

Powderject

Felton international

Glidepharma

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Advantages It is trouble free, simple, self administration Low sensation and safety Solid dosage forms can be administered Elimination of needle phobia Minimal skin response and no bleeding or bruising Easy and safe disposal Easy to transport and store without refrigeration Excellent dose response is observed with increased drug

doses Rapid delivery of the drug to the systematic circulation Bio-equivalence has been demonstrated enabling the

development of ‘generic’ drug proteins

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Conclusion Needle-free technology offers the very benefit of reducing

patient concern about conventional needles and no needle disposal issues.

Not only it can benefit the pharmacuetical industry in increasing product sales, it has the added potentioal to increase compliance with dosage regimens and improved outcomes.

In the developing world, there are major challenges of disease transmission through re-use of needles.

Organizations such as WHO and CDC (Center for Disease Control) and groups like Gates Foundation have supported the development of needle free alternatives for drug delivery.

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The biotech revolution is bringing in a range of protein-based therapeutics into the market place at a rapid pace more than 300 products in active development.

These protein-based therapeutics especially monoclonal antibodies (Mabs) which are anticipated to represent 30 percent of pharmaceutical sales and which are otherwise challenging to deliver non-invasively, will continue to be formulated as injectables.

It is likely that dramatic change may occur only when a large pharmacuetical or biotechnology company adopts needle free technology and demonstrates its versatility, acceptance and value in major therapeutic area

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References

Wikipedia

www.fda.gov

www.glidepharma.com

www.cdc.gov

www.bioject.com

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http://www.fda.gov/

http://www.glidepharma.com/

http://www.cdc.gov/

Documents

Needle Free Injection Systems