1. PACKAGING OF TABLETS:
TYPES, MATERIALS AND QC.
PRESENTED BY: AKSHAY JOSHI
M.PHARM SEM II
GUIDED BY:
DR. A.R MADGULKAR.
Principal: AISSMS COP, PUNE.
1
3. INTRODUCTION:
Packaging is the science, art and
technology of enclosing or protecting
products.
Packaging can be described as a
coordinated system of preparing goods for
transport, warehousing, storage, sale, and
end use. 3
4. NEED OF PACKAGING
Physical protection
Barrier protection
Agglomeration
Security
Convenience
Dose control
4
6. CHARACTERISTICS
Protection From Environmental Conditions
Non-reactive With The Product
Not Impart Taste Or Odor to the Product
Non-toxic,
Adoptable To Commonly Employed High Speed
Packaging Equipments
Meet Applicable Tamper Resistance
Requirements
6
8. Secondary packaging is outside the primary
packaging –used to group primary packages
together
8
9. Tertiary packaging is used for bulk handling
, warehouse storage and transport shipping. The
most common form is a palletized unit load that
packs tightly into containers.
9
12. BLISTER PACKAGING:
Blister packaging is a type of pre-formed
plastic packaging used for small consumer
goods.
The two primary components of a blister
pack are the cavity made from either plastic
or aluminium - and the lidding, made
from, paper, plastic or aluminium.
The cavity contains the product and the
lidding seals the product in the package.
12
15. BLISTER PACKING COMPONENT
The four basic components of pharmaceutical blister
packages are;
1. The forming film (Forming films account for
approximately 80–85% of the blister package)
2. The lidding material (lidding materials make up
15–20% of the total weight of the package.)
3. Heat seal coating
15
16. THERMOFORMABLE MATERIAL
Forming film:
―The forming film is the packaging component that
receives the product in deep drawn pockets.‖
One key to package success is selecting the right
plastic film for the blisters in terms of its;
1. Property/ type,
2. Grade,
3. Thickness.
For example, monolayer PVC film, PVC/PVDC
duplex, PVC/PE/PVDC triplex and PVC/ALCAR
laminate.
16
17. MONOLOYER
POLY(VINYL CHLORIDE) PVC
Rigid PVC.
Very clear, stiff material with a low WVTR.
Excellent thermoformability.
Low permeability.
Low cost.
Good chemical resistance.
Pvc films that are thermoformed have a
thickness of about 10–15 mm.
17
18. POLYVINYLIDENE CHLORIDE
(PVDC)–COATED PVC.
PVDC is the most common coating in blister
packaging because it can reduce the gas
and moisture permeability of PVC blister
packages by a factor of 5–10.
Coated PVC films have a thickness of 8–10
mil; the thickness of the PVDC coat
amounts to 1–2 mil.
The coating is applied on one side and
usually faces the product and the lidding
material.
18
19. Excellent oxygen and moisture barrier
properties as compared to normal PVC
film.
Good thermoformability; PVDC is very cost-
effective, as coating weight can be
customized depending on
the requirements of the barrier properties.
Medical grade and non-toxic.
High levels of transparency which improves
the aesthetics of the product.
19
20. PVC/CHLOROTRIFLUOROETHYLENE
(CTFE).
Films made from PVC and CTFE have the
lowest water-vapour permeability of all films
used for blister packaging.
When compared with the water-vapor
permeability of 10-mil PVC, the permeability
of 8-mil PVC/0.76- mil CTFE is lower by a
factor of 15.
However, the environmental concerns
regarding PVC also apply to PVC/CTFE
films.
20
21. POLYSTYRENE (PS)
Polystyrene (PS) is perfectly compatible with
thermoforming, but its high water vapor
permeability makes it unsuitable as a blister
material for pharmaceutical purposes.
21
22. ALUMINIUM BLISTER FOIL
Used in cold foaming technique.
Alu alu packaging.
Good barrier to moisture, vapour and gases.
20 to 25 micron thick.
22
23. VIDEOS:
Lovell Industries - Blister Packaging South Africa
Animation.mp4
DPP-250F blister machine for tablet- Carlos.mp4
23
Fig 2: Blister machine
24. LIDDING MATERIAL:
―The lidding material provides the base or main
structural component upon which the final
blister package is built‖
After the tablets have been properly fed to the
preformed support materials the lidding material is
sealed onto the support material.
Temperatures for this can range from 140-300 C.
24
25. Lidding materials can also use soft
(annealed) foil (0.025 mm) or laminations of
soft foil and other substances (tissue paper).
Soft and embossed soft foil extends in the
push-through stage, hence may give added
child safety provided it does not damage the
item concerned.
25
26. It must be selected according to;
The size,
Shape,
Weight of the product
Style of the package to be produced.
26
27. An essential component of lidding material is the
sealing coating.
The side of the lidding material that faces the
product and the forming film must be provided with
a coating material suitable for heat sealing.
This is usually accomplished by means of a heat
sealing lacquer
An additional requirement is that the sealing
strength must fall within a predetermined tolerance.
27
28. ALUMINIUM
Push-through, peelable, peel-push, tear-
open and child resistant options.
Tailored solutions for new therapies, new
processes and special applications.
Push-through foil in gauges 15-30 μm, hard
or soft tempered.
Peelable opening in gauges 20 and 25 μm
soft, laminated with PET or paper/PET.
Heat sealable (push-through and peelable
foil) to PVC, PVdC, PP, PET and PE; 28
29. KEY BENEFITS
Broad product range serving all your
application needs and optimising speed-to-
market
Efficiency on blister lines guaranteed with
proven processability
Optimal barrier properties provided by
aluminum foil
High performance ensured by optimised
sealing to thermoformed films.
29
30. PAPER-ALUMINUM.
In Europe, the thickness of the aluminum typically is
0.28–0.48 mil, but in the United States it has a
thickness of 0.6–1 mil.
30
31. PAPER/PET/ALUMINUM.
Lidding material made of a
paper/PET/aluminum laminate is often
called peel off–push through foil.
The concept is to first peel off the
paper/PET laminate from the aluminum and
then to push the tablet through the
aluminum.
31
32. ALU-ALU STRIP
Blister Packing contain PVC foil (0.25mm) and Alu.
foil (0.025mm)
Strip Packing contain Both side Poly alu. foil
(0.30mm)
32
34. COMMENLY USED MATERIALS:
Glass
– type III (solids)
Plastic
– low density polyethylene (LDPE)
– high density polyethylene (HDPE)
– polypropylene (PP)
– polyester PET,
– Cyclo-olefin copolymer (COC)
34
35. GLASS
Widely used.
Advantages of glass:
•It allows easy inspection of the
containers contents
•variable shapes.
Disadvantage of glass:
• It is fragile
• It is expensive when compared to the price
of plastic
35
37. TYPES OF GLASS:
Type I Glass Neutral glass, with a high hydrolytic
resistant due to the chemical
composition of the glass itself.
Type II Glass Usually of soda-lime-silica glass with a
high hydrolytic resistance resulting from
suitable treatment of the surface.
Type III Glass Soda-lime glass usually of soda-lime-
silica glass with only moderate
hydrolytic resistance.
Type IV Glass Non parentral.
37
38. PLASTIC:
LDPE.
It is a thermoplastic made from
the monomer ethylene.
Density range of 0.910–0.940 g/cm3.
Not reactive at room temperatures, (except by
strong oxidizing agents).
No branching.
Withstand temperatures of 80 c continuously.
Made in translucent or opaque variations.
38
39. HDPE:
Polyethylene thermoplastic made from petroleum.
Known for its large strength to density ratio.
HDPE is commonly used in the production
of plastic bottles.
Although the density of HDPE is only marginally
higher than that of low-density polyethylene,
HDPE has little branching, giving it
stronger intermolecular forces and tensile
strength than LDPE.
Harder and more opaque and can withstand
somewhat higher temperatures (110 C
continuously)
39
40. POLYPROPYLENE
An addition polymer made from the
monomer propylene.
it is rugged and unusually resistant to many
chemical solvents, bases and acids.
Has an intermediate level
of crystallinity between that of low-
density polyethylene (LDPE) and high-density
polyethylene (HDPE).
Tough and flexible, especially
when copolymerized with ethylene.
40
42. SECONDARY PACKAGING:
Labels and leaflets
Wrapping materials
bags and sacks
collapsible and rigid cartons and boxes
moulded pulpboard containers
paper liners, linings and laminations.
42
43. PAPER:-
This can be used as a flexible wrap for
products, or as a closure material for jars. Most
paper materials are used with a liner applied either
as a laminate or as a coating.
Paper and board are seen as renewable resources
as distinct from petroleum- and metal-based
resources.
They are not as consistent as synthetic products.
Hence, analyzing them is a problem.
Holocellulose
Lignin 43
44. Holocellulose—this is 70–80% of the wood. It is
the whole water-insoluble carbohydrate fraction
comprising:
alpha-cellulose,
hemi-cellulose,
beta-cellulose,
gamma-cellulose,
Lignin—this varies between 17% and 30% of the
bulk and is an amorphous phenylpropane polymer
which is found
44
46. QUALITY CONTROL FOR TABLET
PACKAGING:
Softening and disaggregation (mechanical
corrosion)
Chemical hydrolysis of the active
ingredients (decrease of potency and/or
forming of toxic compounds)
Oxidation of the active ingredients
(decrease of potency and/or forming of toxic
compounds)
Worst case, fatality can be the result of
decomposition of the product.
46
47. WATER VAPOR TRANSMISSION RATE
Water Vapor Transmission rate is a measure of the
passage of water vapor through a membrane.
It is the rate of water vapor transmission per unit
area per unit of vapor pressure differential under
test conditions.
It is an index of the ability of materials barrier water
vapor.
Higher water vapor transmission rate, poorer water
vapor barrier property, shorter shelf life of products
47
49. OXYGEN TRANSMISSION RATE
Is the steady state rate at which oxygen gas
permeates through a film at specified conditions of
temperature and relative humidity.
Value is expressed in cc/100 in2/24 hr in US
standard units and cc/m2/24 hrs. in metric (or SI)
units.
49
50. BLISTERSCAN
Blisterscan (SEPHA
industries), a laser-
based leak detection
machine, test
method detected
100% of 15μm sized
holes, while only
85% of such defects
were picked up by
blue dye testing.
50
51. BROOKFIELD CT3 ANALYZER
The TA-BPS has been developed to
calculate the force needed to push the
pill through a blister pack.
The V2 inch radius Finger Probe,
replicating a human finger, is pushed
down onto the tablet at a steady speed,
forcing the tablet through the foil.
Peak load is the main information from
this test which is the maximum force
noted during the probe’s descent on the
package.
Strength of the blister pack .
51
53. PACKAGING DEVELOPMENT
Objective
To ensure timely and robust selection of the
primary pack for clinical trial and commercial
supply.
Recommended approach:
To use, where possible, a limited range of
standard, well-characterised pack materials and
packs.
To ensure thorough testing, characterisation
and understanding of these selected pack
materials and packs. 53
54. COMMERCIAL PACK DEVELOPMENT
Approach:
3. Development Stability Testing
2. Material Selection & Testing
1. Identify Pack Options
5. Pack Selection
4. Controls Defined
54
55. CASE STUDY:
Product: Amoxicillin-clavulanic acid tablets
59 samples were collected from 48 medicine
outlets.
Samples were classified into five types according
to package type and the presence of desiccants
(e.g., silica gel)
55
Type A Press-through packaging (PTP) of aluminium-
aluminium materials in cardboard boxes.
Type B Type A tablets wrapped in transparent plastic with
silica gel.
Type C Type A tablets wrapped in aluminium with silica gel.
Type D Similar to Type C, but with PTP made of an
aluminium-plastic composite.
Type E Strip packaging (SP) in cardboard boxes without
silica gel.
56. A stability test was conducted on
amoxicillin/clavulanic acid at 37 C with 100%
relative humidity (RH).
They used one control sample with no visible
defect, one with torn wrapping but no strip
defect, and one in which the strips were deliberately
perforated.
In all three samples, amoxicillin and clavulanic acid
contents were measured at 0, 24, 48, 72, and
96 hours.
8 failed dose requirements
10 content uniformity and 20dissolution tests
56
58. DISCUSSION
Interestingly, clavulanic acid accounted for most
failures in the quantity and content uniformity tests
(87.5% and 70% of failures, respectively), whereas
amoxicillin accounted for most failures (80%) in the
dissolution tests.
Clavulanic acid is volatile and unstable when
exposed to high temperatures and high pH.
In addition, clavulanic acid is hygroscopic;
therefore, 30% RH or less is desirable for storage
Samples that failed the content uniformity test
usually came from open packages/containers
during sampling 58
59. SUMMARY
Packaging is one of the most important part of
pharmaceutical industries
Quality maintenance is measure role played by
packaging material
Along with that it gives pharmaceutical elegance and
convenience to user to product
Many a times the packaging may become a ideal unique
identification for some of brand in market
Quality control of such important part is also a vary
valuable work
59
60. REFERENCES.
Ambrosio TJ. Packaging of pharmaceutical Dosage
forms. In: Gilbert S Banker & Christopher T
Rhodes, editor. Modern Pharmaceutics. 3rd ed.
Florida: Taylor and Francis group;1996. P. 483-485.
(Drugs and the Pharmaceutical Sciences; vol 72)
Dean D.A. Blister, Strip and Sachet Packaging
Evans E.R, Hall I.H. editors, Pharmaceutical
Packaging Technology, 11 New Fetter Lane,
London 2005. P. 370.
Ebewele RO. Chapter Four Thermal Transitions in
Polymers, Polymer Science And Technology, P. 553
CRC Press Boca Raton New York
60
61. REFERENCES.
Yam KL. Editor,Encyclopedia Of Packaging
Technology, Third Edition, A John Wiley & Sons,
Inc., Publication 2009, P 464-465.
Lachman L, Liberman HA, Packaging Material
Science, The Theory and Practice of Industrial
Pharmacy, CBS Publishers,2009 P 711-733.
http://www.ask.com/question/what-is-blister-
packaging ( last accessed on 14-04)
Pilchik R, Pharmaceutical Blister Packaging, Part I,
Rationale and Materials, Pharmaceutical
Technology NOVEMBER 2000.
http://pharma.financialexpress.com/20040624/techn
ologytrendz01.shtml ( last accessed on 18-04)
61
62. REFERENCES.
http://www.amcor.com/products_services/BLISTER
_LIDDING.html ( last accessed on 14-04)
http://formulation.vinensia.com/2012/01/glass-for-
pharmaceutical-packaging-and.html ( last accessed
on 17-04)
http://www.azom.com/article.aspx?ArticleID=8034 (
last accessed on 21-04)
―INDIAN PHARMACOPOEIA 2007‖, Volume-1, published by
The Indian Pharmacopoeia Commission, Central Indian
pharmacopoeia Laboratory Govt. Of India, Ministry of Health
& Family Welfare Sector-23, Raj Nagar, Ghaziabad-201 00
Page no. 363-371
―UNITED STATES PHARMACOPOEIA 2007‖,Volume-1,Page
no.661
62
63. REFERENCES.
Khan MH,Hatanaka K. Effects of packaging and
storage conditions on the quality of amoxicillin-
clavulanic acid – an analysis of Cambodian
samples, BMC Pharmacol Toxicol. 2013; 14: 33.
63
