Container and closure for pharmaceutical

1. CONTAINERS AND CLOSURES FOR
PHARMACEUTICALS
Presented by:
Vaishnavi V. Fatangare
F. Y. M. Pharm
Dept. of Quality Assurance
Roll No. MQA04
Guided By:
Dr. S. S. Chalikwar
Head of department
Industrial Pharmacy Quality
Assurance
R. C. Patel Institute of Pharmaceutical Education and
Research, Shirpur.
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2. CONTENTS
INTRODUCTION
CLOSURES AND CLOSURE LINERS
TYPES OF TAMPER-RESISTANT PACKAGING
QUALITY CONTROL OF PACKAGING
MATERIAL AND FILLING EQUIPMENT
CONCLUSION
REFERENCE
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3. Pharmaceutical Packaging
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4. INTRODUCTION
• In the pharmaceutical industry, it is vital that the package selected must preserve the
integrity of the product.
• The selection of a package therefore begins with determination of the product’s physical
and chemical characteristics, its protective needs, and its marketing requirements.
• Desirable attributes which a packaging material must have include:
1. Protection of product from environmental conditions (light, gases, moisture etc. )
2. Safety
3. Compatibility
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5. CLOSURES
• The closure is normally the most vulnerable and critical component of a
container in so far as stability and compatibility with the product are concern.
• An effective closure must protect the contents from escaping and allow no
substance to enter the container.
• The adequacy of the seal depends on number of things, such as resiliency of
the liner, flatness of sealing surface on the container and most important
tightness with which it is applied.
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6. Closures are available in different design
Screw cap
Lug cap
Crimp-on (Crown Cap)
Roll-on Closure
Friction Fit Closure
TYPES OF CLOSURE
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7. Screw cap
The screw cap is commonly made of metal or plastics.
The metal is usually tinplate or aluminum, and in plastics, both thermoplastic and
thermosetting materials are used.
Metal caps are usually coated on the inside with an enamel or lacquer for resistance
against corrosion.
When the screw cap is applied, its threads engage with the corresponding threads molded
on the neck of the bottle.
 The lug cap is used for both normal atmospheric pressure and vacuum pressure closing.
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Lug cap

8. Crimp-on (crowns)
 These are friction fitting closure types.
 This style of cap is commonly used as a crimped closure for beverage
and has remained essentially unchanged for more than 50 years.
 Crown is made of tin free steel and tin plate.
Roll-On Closure
 The aluminum roll-on cap be sealed securely, opened easily and released effectively.
 The roll-on closure requires a material that is easy to form, such as aluminum or other
light-gauge metal.
 Resealable, non-resealable and pile proof types of the roll-on closure are available for
use on glass or plastic bottles and jar.
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9. Friction Fit Closure
 Friction-fit closures rely on a number of different methods to create friction or some
type of interference fit between the closure and the bottle.
 They are most often used on glass containers but can be used on specialized plastic containers
if the strain produced by the friction fit does not cause undue creep or cold flow of the plastic.
There are four different types of friction closures widely used:
A. Bottle crowns
B. Snap-fit closures
C. Press-on closures
D. Elastomeric stoppers
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A B
C D

10. Tamper Resistance Closures
 Tamper-Evident Closure are typically lids for plastic and glass bottles used in the
packaging and pharmaceutical industries.
 The closures are positioned mechanically and a seal needs to be broken in order to open
them, which leaves an obvious visual indication that the bottle has been opened.
a) It lesion the risk of harmed products.
b) It advances security.
c) It increases costumer loyalty.
Advantages: -
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11.  Child resistant packaging or CR packaging is special packaging to reduce the risk of
children ingesting hazardous materials.
 These is often accomplished by use of special safety cap or closure.
 These closures are easily opened by adults with simple “push down and turn” motion.
 The consumer product safety commission (CPSC) commands CRC packaging.
 If your product contains any potentially harmful substances such as medicine or
chemicals that could be hazardous if taken in wrong dose such conditions require
child-resistant closure packaging.
Child-Resistant Closures
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12. Dispensing closure
 Dispensing closures allows a specific amount of product to be dispensed each time
the product is used.
 It eliminate the wastage of product as a bottle or other package does not need to be
fully opened, it improves the shelf life of product.
 These closure come in different neck size to ensure a tight fit and also with orifice
sizes that suit product and size of the container.
 The dispensing adds to the perceived product value that automatically increases when
compared to simple disc top closure that does not provide dispensing convenience.
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13. Closures Composition: -
Closure
Glass
Metal
Rubber
Cork Plastic
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14. Closure Liner
 Liner may be defined as any material that is inserted in a cap to effect a seal
between the closure and the container.
 Liners are usually made of a resilient backing and a facing material.
 The backing material must be soft enough to take up any irregularities in the
sealing surface and elastic enough thick enough to recover some of its original
shape when removed and replaced.
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15. Factors in Selecting a Liner:-
• Compatibility
• Appearance
• Gas and vapor transmission rate- WVTR, Oxygen etc.
• Removal torque
• Heat resistance
• Shelf-life
• Economic
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16. Homogeneous Liner:-
These one-piece liners are available either as a disk or as a ring of rubber or plastic.
Although they are more expensive and more complicated to apply, they are widely used
for pharmaceuticals because their properties are uniform and they can withstand high-
temperature sterilization.
Heterogeneous or Composite Liners:-
These are composed of layers of different materials chosen for specific requirements. In
general, the composite liner consists of two parts:
Face & Back
Usually, the facing is in contact with the product and the backing provides the
cushioning and sealing properties required.
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17. TAMPER RESISTANT PACKAGING
• As defined by the FDA, “a tamper resistant package is one having an indicator or barrier to
entry which, if breached or missing, reasonably be expected to provide visible evidence to
consumers that tampering has occurred.”
• The definition is found in 21 CFR 211.132
• Products that require tamper-evident packaging are:
1. OTC drug products.
2. Oral, rectal, nasal, vaginal, otic, and ophthalmic products.
3. Oral cosmetic liquids, including mouthwashes, gargles, and breath fresheners.
4. Contact lens solutions and the cleaning supplies and tablets used for their maintenance.
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18. • FDA examples of Tamper-Resistant Package forms (Nov. 1982):
• which are capable of meeting the requirements of tamper resistant packaging
defined by FDA regulation 21 CFR parts 211, 314, 700.
Bubble packs
Shrink package
Bottle seal
Tape seals
Breakable seal
Sealed tubes
Film wrapper
Blister packs
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19. Film wrappers
Film wrapping has been used extensively over the years for products
requiring package integrity or environmental protection. It has
categorizes into following types :
1. End folded wrapper
2. Fin seal wrapper
3. Shrink wrapper
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20. The end folded wrapper is formed by passing the product into a sheet of over wrapping
film, which forms the film around the product and folds the edges in a gift wrap fashion.
The folded areas are sealed by pressing against a heated bar.
The materials commonly used for this purpose are cellophane and polypropylene.
End folded wrapper
The seals are formed by crimping the film together and sealing together the two inside
surfaces of the film seal.
Fin sealing is superior than end folded wrapper with good seal integrity the over wrap
can removed or opened by tearing the wrapper.
Fin seal wrapper
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21. • The wrap concept involves the packaging of the
product in a thermoplastic film that has been
stretched and oriented during its manufacture.
• An L shaped sealer seals the over wrap.
• The major advantage of this type of wrapper are the
flexibility and low cost of packaging equipment.
Shrink wrapper
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22. Blister packs
• The blister package is formed by heat softening sheet of thermoplastic and vacuum-
drawing the softened sheet is released from the mold and proceeds to the filling station of
the packaging machine.
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• The semi rigid tray is previously formed is filling with
tablets/capsules and lidded with a heat sealable backing material.
The backing material is usually heat seal coated aluminum foil.
• The plastic material used includes PVC, polyethylene
combination.

23. Bubble Pack-
• The bubble pack can be made in several ways but is usually formed by sandwiching
the product between a thermoplastic film and a rigid packing material similar to a sin
blister.
• Accomplished by heat-softening the plastic film and vacuum-drawing a pocket into
the film in a manner similar to the formation of a blister package.
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24. • The shrink band concept makes use of the heat shrinking characters of a stretch oriented
polymer usually PVC.
• The heat shrinkable polymer-PVC is manufactured as a tube in a diameter slightly larger
than the cap and neck ring of the bottle to be sealed.
Shrink Banding-
Shrink Banding
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• This is the placed over the bottle cap and the package
through a heated tunnel, which shrinks the plastic cover
around the cap, preventing the disengagement of the cap
without destroying the shrink band .

25. Bottle seal
• A bottle may be made temper resistant by bonding and inner seal to the rim of the bottle
in such a way that the product can only be attained by destroying the seal.
• Typically glassine liners are two ply laminations use in two sheet of glassine paper
bounded together with wax or adhesive.
• For pressure sensitive inner seals pressure sensitive adhesive is coated on the surface of
the inner seal as an encapsulated adhesive .
Tape seals
• It involves the application of glued or pressure sensitive tape or label around or over the
closure of the package which is to be destroyed to obtain the product.
• The paper used must often is a high density light weight paper with poor tear strength.
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26. Breakable seal
• The container is sealed by a plastic or metal cap that either breaks away completely when
removed from the container or leaves part of the cap attached to the container. The cap
must be broken to open the container and remove the product.
• Breakable closures come in many different designs.
• The bottom portion of the cap is rolled around the bottle neck finish.
• The lower portion of the cap blank is usually perforated so that it breaks away when the
cap is unscrewed. The bottom portion of the closure has a tear away strip.
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27. • Collapsible tubes used for packaging are constructed of metal, plastic or
lamination of foil, paper and plastic.
• Metal tubes are still used for products that required high degree of barrier
protection, most of those are made of aluminum.
• Extruded plastic tubes are widely used for products that are compactable and
limited protection of plastic.
Sealed Tubes
Significance –
1. Extra strong and secure packaging.
2. Regulations for some pharmaceuticals require it.
3. Extra layers of packaging.
4. Packages can not be resealed .
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28. • A number of quality control checks are required for the manufacture
and release of container-closures.
These include:
a) After the material has been mixed
b) Post-compression and molding
c) Washing process
d) Post-washing and post-Siliconization
e) Packaging After packaging
f) Sterilization
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Quality control of packaging material

29. • Specific gravity
• Color Dispersion in relation to particle size
• Hardness
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1. After the material has been mixed
2. Post-compression and molding
• Here the material is checked for rubber thickness
3. Washing process
• During the loading of stoppers into a washer, the quality of the water should be
checked for bio burden and endotoxin (using compendial methods).

30. After the stoppers have been washed, a number of quality control checks should be
performed. These include:
1. MECHANICAL AND MATERIAL TESTING
2. PHYSICAL TESTS
3. CHEMICAL TESTING
4. BIOLOGICAL TESTS
A selection of bags should be examined for integrity as a part of quality control
assessment.
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4. Post-washing and post-siliconization
5. Packaging after packaging

31. 6. Sterilization
Container-closures are typically sterilized by one of two methods:
• Steam sterilization (using autoclaves) and
• Gamma irradiation
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32. Quality control of filling equipment
The specific method used for filling a pharmaceutical liquid varies greatly
depending on the characteristics of the liquid, the type of package into which
the liquid is placed and the required production output.
Three basic filling methods -
1. Gravimetric
2. Volumetric and
3. Constant level
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33. • Filling containers to a given weight is generally limited to large containers or to
highly viscous products.
• The process does not readily lend itself to high-speed, automatic equipment.
Gravimetric filling
Volumetric filling
• Done by positive displacement piston action. Each filling station is equipped with a
measuring piston and cylinder.
• The fill amount is measured by the stroke of the piston, which on all machines can
be varied to a limited degree. Major changes in fill amount usually necessitate
changing the piston and cylinder assembly.
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34. • It uses the container as the means for controlling the fill of each unit. The fill
amount is varied by adjusting the height to which the container is filled.
• Any dimensional variations in the containers result in comparable variations in
the net fill per unit.
• This method of filling is usually slow and is rarely used when high production
rates are required.
Constant-level
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35. • The most widely used methods can be broadly classified into three
categories:
To fill by vacuum, a seal must be made between the filling head and the container. A
vacuum is then developed within the container, which causes the liquid to flow from the
bulk liquid tank to the container. The liquid level rises until it reaches the vacuum tube,
which is positioned at the desired constant level. Excess liquid is drawn through the
vacuum tube and can be recycled to the bulk liquid tank.
Vacuum filling
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• The vacuum drawn through tube C reduced pressure in the container.
Pressure differential causes liquid in storage tank to flow through tube B
into container. When liquid level reaches point A, excess is carried out
through tube C and may be recycled to liquid storage tank

37. A positive pressure is applied to the bulk liquid, which in combination with the
vacuum developed in the container, results in a pressure differential that allows for
rapid filling of even highly viscous liquids.
In gravity-vacuum filling, the bulk liquid tanks are a level above the filling stem, so
that the driving force for liquid flow results from both the negative pressure in the
container and the force of gravity.
Gravity-vacuum filling
Pressure-vacuum filling
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38. The container-closure system is an essential part of the final presentation of a
pharmaceutical product. It defines the closure, protection, and functionality of a
container while ensuring the safety and quality of the drug product over the product
shelf life. This presentation has focused upon the important tests, control measures,
and essential aspects for ensuring that the product, in its final packaging, is fit-for-
purpose prior to the administration of the drug.
Conclusion
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39. REFERENCES
1. Lachman/Lieberman’s the theory and practice of industrial pharmacy , page no-
1024-1030.
2. Modern Pharmaceutics 4th Edi. Revised & Expanded by Banker and Rhodes
3. Edward J Bauer. Pharmaceutical Packaging Handbook. 2009. Informa Health care
USA Inc. New York.
4. Dean D A, Evans E R and Hall I H. Pharmaceutical Packaging Technology. London,
Taylor & Francis, 1st Edition. UK.
5. Prepared by Mrs. M. JANANI Department of commerce (INTERNATIONAL
BUSINESS). https://gacbe.ac.in/pdf/ematerial/18BIB55S-U1.pdf Date-06/07/2023
Time- 2.33pm.
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