m
  





› Prepared by Satish kumar K

› Guided by Ramakrishna
› Department of Industrial
Pharmacy

17 Feb 2011 Sree Datta Institute of Pharmacy 1

 „


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

17 Feb 2011 Sree Datta Institute of Pharmacy 2

 




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

17 Feb 2011 Sree Datta Institute of Pharmacy 3

 m
  

£ 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)

17 Feb 2011 Sree Datta Institute of Pharmacy 4

 m
     


   

£ 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
17 Feb 2011 Sree Datta Institute of Pharmacy 5
   



17 Feb 2011 Sree Datta Institute of Pharmacy 6

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corneocytes + lipid
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thin layer
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produces lipids
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numerous layers
start of differentiation
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one layer
cell division
17 Feb 2011 Sree Datta Institute of Pharmacy 7
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The skinµs diffusional barrier

17 Feb 2011 Sree Datta Institute of Pharmacy 8

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17 Feb 2011 Sree Datta Institute of Pharmacy 9

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The dermisµ mechanical property

17 Feb 2011 Sree Datta Institute of Pharmacy 10

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17 Feb 2011 Sree Datta Institute of Pharmacy 11

   


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

17 Feb 2011 Sree Datta Institute of Pharmacy 12

17 Feb 2011 Sree Datta Institute of Pharmacy 13
  

› 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.

17 Feb 2011 Sree Datta Institute of Pharmacy 14

› 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.

17 Feb 2011 Sree Datta Institute of Pharmacy 15

17 Feb 2011 Sree Datta Institute of Pharmacy 16
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(Needle & Needle-Free)

17 Feb 2011 Sree Datta Institute of Pharmacy 17

 Comparison with Percutaneous Absorption

Diffusion

Dissolved Partition: ü¬ {
Drug

Diffusion/Partitioning Process
Major diffusional barrier is stratum corneum
- morphology gives altered A* and l*
- Lw lipid structure
17 Feb 2011 Sree Datta Institute of Pharmacy 18
 Needle/Needle-Free Injection

Needle

NF- liquid

NF- powder

- Tissue penetration via needle or substance (fluid/particles)

projected from needle-free device
- puncture (mechanical failure) of epidermis & dermis
- deformation of dermis/hypodermis

17 Feb 2011 Sree Datta Institute of Pharmacy 19

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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

17 Feb 2011 Sree Datta Institute of Pharmacy 20

 m
  
 


#
&  %

£ Spherical bolus Amplified Dispersion

- Lowest possible - Very high
SA/V ratio SA/V ratio

- Limited tissue - Enhanced tissue

disruption disruption

17 Feb 2011 Sree Datta Institute of Pharmacy 21

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- 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

17 Feb 2011 Sree Datta Institute of Pharmacy 22

î 
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*

 

A Puncture & deformation of skin tissue is complex

issue !
A Requires knowledge of biomechanical properties of
skin tissue
A Problem: biomechanical behaviour of skin is
inhomogeneous, non-linear (depends on stress rate)
& anisotropic
A 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)

17 Feb 2011 Sree Datta Institute of Pharmacy 23

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£ Part 3: Biomechanical Properties

of Human Skin

17 Feb 2011 Sree Datta Institute of Pharmacy 24

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- Various experimental setups possible:

1. Stretching measurements in vitro & in vivo

- stress versus strain

2. Compression measurements

3. Fracture resistance

4. Ultrasonic measurements

17 Feb 2011 Sree Datta Institute of Pharmacy 25

 a  ' 
  
,-

.  
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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

17 Feb 2011 Sree Datta Institute of Pharmacy 26

 a  ' 
  
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Can apply up to 70 N force to skin

Maximum deformation of 30 mm

17 Feb 2011 Sree Datta Institute of Pharmacy 27

 a  ' 
  
0-
  
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FR = energy required to separate a tissue sheet into 2 pieces [J/m2]

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

dissipation)

17 Feb 2011 Sree Datta Institute of Pharmacy 28

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17 Feb 2011 Sree Datta Institute of Pharmacy 29

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› Unique morphology defines the skinµs 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)

17 Feb 2011 Sree Datta Institute of Pharmacy 30

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î V  V V
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V

17 Feb 2011 Sree Datta Institute of Pharmacy 31

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Epidermis Dermis Hypodermis

P High pressure liquid jet emerges from nozzle

- 150 ± 200 mm , - velocity
100 m/s
- static pressure
10 MPa on skin surface
PLiquid jet punctures skin tissues
- forces related to needle penetration force
PLiquid jet disperses in dermis(D) & hypodermis (HD)
- force sufficient to overcome Youngµs modulus of
D/HD (10 ± 100 kPa)
- dose volume small = assumption of linear elasticity

17 Feb 2011 Sree Datta Institute of Pharmacy 32

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17 Feb 2011 Sree Datta Institute of Pharmacy 33

  

› 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).

17 Feb 2011 Sree Datta Institute of Pharmacy 34

 a

)))-"
- 

Cool click

pharmaject

bio2000

17 Feb 2011 Sree Datta Institute of Pharmacy 35

 a

a  
)%%%
Designed for the professional healthcare
market
- Immunization programs
- Hospitals
- Clinics

  
V
Spring powered
CO2 powered with electronics

17 Feb 2011 Sree Datta Institute of Pharmacy 36

 a
 
 "
 

17 Feb 2011 Sree Datta Institute of Pharmacy 37

 Other well known manufacturers are :

› Powderject

› Felton international

› Glidepharma

17 Feb 2011 Sree Datta Institute of Pharmacy 38

 ©

 
£ 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 µgeneric¶ drug proteins

17 Feb 2011 Sree Datta Institute of Pharmacy 39

 „ 
£ 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.

17 Feb 2011 Sree Datta Institute of Pharmacy 40

£ 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

17 Feb 2011 Sree Datta Institute of Pharmacy 41

     
£ Wikipedia

£ www.fda.gov

£ www.glidepharma.com

£ www.cdc.gov

£ www.bioject.com

17 Feb 2011 Sree Datta Institute of Pharmacy 42