WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Jadhav et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Volume 3, Issue 5, 194-204.

Review Article

ISSN 2278 4357

ADVANCES IN PHARMACEUTICAL PACKAGING

*Ghanshyam Balkrishna Jadhav, Amar Gangadhar Zalte,
Ravindranath Bhanudas Saudagar
Department of Quality Assurance, R. G. Sapkal College of Pharmacy, Anjaneri, Nashik.

Article Received on
26 February 2014,
Revised on 25 March
2014,
Accepted on 21 April 2014

ABSTRACT
A stability and integrity of a pharmaceutical product can be maintained
by packaging of a product in a proper way. Packaging plays an
important role in providing protection, presentation, convenience,
identification information, and compliance of a product during storage,

*Correspondence for Author

Dr. G. B. Jadhav
Department of Quality

transportation,

display

and

until

the

product

is

safely

consumed.Packaging may be considered as a system by which the

Assurance, R. G. Sapkal

product safely reaches from producer to consumer. The review mainly

College of Pharmacy, Anjaneri,

focuses on recent advances in packaging technology and packaging

Nashik.

material.
Keywords: Pharma packages, Closures and containers and Pharmaceutical packages.
INTRODUCTION
Packaging is the science, art and technology of enclosing or protecting products for
distribution, storage, sale and use. A final product is not accepted except it is properly
packaged, and in some cases the major part of the formulation process may be concerned
with selecting the correct package for the product. Packaging also refers to the process of
design, evaluation and fabrication of packages. A package consists of the container, closure,
carton and box components. The containerrefers in which the final product is enclosed for
distribution from manufacturer to consumer. Closure provides tight packing to a container.
Carton is used for outer covering, which gives secondary protection against mechanical and
other environmental hazards and in the box multiples of products are packed. Designing of
package starts with the identification of all the requirements such as structural design, quality
assurance, marketing, logistics, shelf life, legal, graphic design, end-use, regulatory and
environmental etc1. While selection of package for pharmaceuticals following criteria should
be considered.
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PACKAGE RAW MATERIAL APPROPRIATE FOR DOSAGE FORM

RELATIVE BARRIERS, INERTNESS AND PROPERTIES OF PACKAGING MATERIAL
METHODOLOGY AND EXPERIMENTAL SCHEME TO CHECK EFFECT ON SHELF LIFE
TESTS AND PROCEDURES TO ENSURE REPRODUCABILITY OF PRODUCT QUALITY
PACKAGE INTEGRITY IN CHEMICAL, MECHANICAL AND CLIMATIC HAZARDS
Figure 1: Criteria for selecting proper packaging system for pharmaceutical product2
Packaging of pharmaceutical products has come a long way in India and world scenario.
Recently pharmaceutical industries look a lot colourful packs, beautiful transparent bottles
and also with a barcoding system of labeling.
Packaging systems can be categorized as follows,

Figure 2: Various Packaging Systems

Many types of symbols for package labeling should be nationally and internationally
standardized. Packaging symbols represent product certifications, trademarks, proof of
purchase.3
Advantages of Packaging
Packaging System Provides following advantages they are as follows,
UNIFORMITY
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INTEGRITY
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ADVANTAGES OF
PACKAGING
GOOD STABILITY WITH A CLEARLY
DEFINED SHELF-LIFE PROFILE

MINIMUMSIDE-EFFECTS

Figure 3: Advantages of Pharmaceutical Packaging4.

Advances in Packaging System
Blow- fill- seal technology
Blow- fill- seal technology was initially used for filling many categories of liquids, such as
non-sterile devices, foods and cosmetics. Recently, Blow- fill- seal technology is used to
produce aseptically sterile pharmaceuticals such as respiratory solutions, ophthalmics, and
wound care products. Blow- fill- seal is an advanced aseptic processing techniquewithin
which plastic containers are formed by meansof moulded extruded polymer granules that are
filledand sealed in one continuous process.Due to the advaced automation of the entire
process,very little human intervention is necessary duringmanufacture as compared to
traditional aseptic filling.This is considered an advanced aseptic filling process.It is therefore
possible to achieve very high levels ofsterility confidence with a properly configured Blowfill- seal machine designed to fill aseptically5.
Ouline of Blow- fill- seal process
Technique mainly involve three steps
1.Container molding
2.Container filling
3.Container sealing
1. Container molding
Thermoplastic granules are continuously extruded in a tubular shape. After that tube reaches
to a correct length,the mould closes and prison is cut. The bottom of the prison is pinched
closed and the top is held in place with a set of jaws. The mould further transferred under a
filling station6.

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2. Container filling
The nozzle assembly lowers into the prison until the nozzles form a seal with the neck of the
mould. Container formation takes place in a mould by blowing ansterile filtered air inside the
container. The nozzles come into their original position. The patented automated devices are
available in the market6.
3. Container sealing
After completion of filling the top of a container is sealed hermatically and filled, sealed
container is thrown out of the machine6.
Tamper Evident Pharmaceutical Packaging7
Tamper evident pharmaceutical packaging can be defined as Packaging having an indicator
or barrier to entry which, if breached or missing, can reasonably be expected to provide
visible or audible evidence to consumers that tampering has occurred. Tamper-evident
packaging involves immediate-container/carton systems or any combination.
Types and effects of product tampering
Tampering can be classified into five types
1. Criminal tampering
One or more contaminated products are kept on the shelf so as the consumers may purchase
and he should consume the adulterated product without any knowledge about quality of a
product.
2. Staged tampering
Purposely the final product is contaminatedsuch that to simulate that the manufacturer has
been the victim of true tampering. An example is the Seattle case where staged tampering
was used to cover a murder. Tampering is also used in suicides to try to gain money for their
family and cover the true manner of death.
3. Extortion tampering
If offenders demands are not met, they usually threatens to tamper with a product. These
demands are always for substantial amount of money.
4. Faked tampering
An offender gives alert to media, law enforcement, relevant manufacturers, or others of a
non-existent tampering. Many of the alerts are given for entertainment.
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5. Suspected tampering
Consumersgives alert to the manufacturer when a compromise is done with the package
compromised. It leads to unusual appearance of a product, or condition may arise a consumer
sufferedwith a particular symptoms after the consumption of the product. The consumer
complaints are usually due to compromise in quality, defects due to machinery and failures
rather than tampering. For example Unevenness in quantity of a product, burns on package
seals, damage to the packaging caused by careless opening of cartons in retail stores.
Various advanced technologies of making a Tamper-Evident Package
1. Induction cup sealing technology
2.Induction wads
3. Heat shrink bands or wrappers
1. Induction cup sealing technology
Induction Cup sealing technology is used to create airtight and hermetic seals on the neck of
the container. The seal should be strong, flexible yet easy to remove and provides protection
against cross contamination and an effective tamper-evident layer. The process of Induction
cup sealing is based on the principle that a conductive material like aluminum foil heats up on
exposure to high frequency magnetic field generated by an induction unit. This is a non contact process without direct heat transfer. Due to this, the sealable closure liner can be
placed in the cap by the manufacturer prior to sealing. The Induction Sealing process can be
very easily incorporated on any existing filling lines from manual filling to the fully
automated filling and capping lines. The Induction unit can have its own conveyor or can be
mounted on the existing conveyor line. Separate operation of sealing foil and lid assembly are
no longer required.
2.Induction wads
The current is supplied to seal, due to flow of current temperature increases and seal get
adhere to a top of a container. After the seal is broken, the board or foam packing is retained
by the cap. Wads for HDPE, LDPE, PET and PP in different thickness are easily available
It consists of four layers they are as follows
a. Cardboard or Foam Packing
b.Wax Layer
c. Aluminum Foil
d. Sealing Film
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3. Heat shrink bands or wrappers

Polymers like PVC has characteristics of heat-shrinking which can be used to prepare heat
shrink wrappers. The polymer is manufactured as an extruded, oriented tube in a diameter
slightly larger than the cap and neck ring of the bottle to be sealed. Bands or wrappers with a
distinctive design (e.g., a pattern, name, registered trade mark, logo, or picture) are shrunk by
heat to seal the union of the cap and container. The seal must be cut or torn to remove the
product. The band or wrapper cannot easily be worked off and reapplied without visible
damage to the band. Use of a perforated tear strip can enhance tamper evidence. Cellulose
wet shrink seals are not acceptable as the knowledge of how to remove and reapply these
seals without evidence of tampering is widespread.

Figure 4: Heat shrink band

4. Closed vial technology
To improve aseptic filling quality and processing quality a closed vial technology has been
developed. A sterile vial is filled by inserting a non- coring needle through the stopper which
is then released by laser. The vial body and the stopper are molded are assembled in class 100
area which prevent entry of particles.6
5. Pouches, Sachets and Form Fill Seal Packs
The product is enclosed in an individual pouch or sachet that must be ripped, peeled open or
broken to gain access to the product8.
6. Bubble Pack
The bubble pack can be made in several ways but is usually formed by sandwiching the
product between a thermoform able, extensible, or heat-shrinkable plastic film and a rigid
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backing material9.
7. Novel Laser Coding Technology for Pharmaceutical Glass Containers
Glass syringes can now be individually coded / safe process free of micro-cracks / Reliable
Track & Trace. A completely new laser-coding system enables glass containers for parenteral
use to be clearly coded at the glass syringe manufacturer and tracked from production to end
customer. This innovation can help pharmaceutical companies to develop a reliable Track &
Trace system and further reduce the risk of mix-up of syringes and batches. The benefit of
this technique is patient safety for pharmaceutical and diagnosticproducts is guaranteed. The
laser-coded containers meet the demands of clean room standards and no additional
chemicals or materials are required for coding. Various tests have proven that the laser
coding causes no microcracks and has no effect on the mechanical stability of the glass. The
2D data matrix code which is marked on to the container is barely visible to the human eye
but allows for the indexing of a database record which contains data related to the individual
item, such as drug specification, dosage, production line and batch. The process can be used
for syringes as well as for vials, cartridges and ampoules10.
International standards on packaging
A list is given below of the standards on packaging issued by theInternational Organization
for Standardization (ISO), as of 10 October 1998, starting with the four main standards, after
which they are listed in numerical order.
Quality systems model for quality assurance in design, development, production,
installation and servicing. International Standard ISO 9001. 1994.
Quality systems model for quality assurance in production, installation and servicing.
International Standard ISO 9002. 1994.
Quality systems model for quality assurance in final inspection and test. International
Standard ISO 9003. 1994.
Quality management and quality systems elements. Part 1:GuidelinesInternational Standard
ISO 9004-1. 1994.
Quality management and quality systems elements. Part 2:Guidelinesfor service.
International Standard ISO 9004-2. 1994.
Quality management and quality systems elements. Part 3:Guidelinesfor processed materials.
International Standard ISO 9004-3. 1994.

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Quality management and quality systems elements. Part 4:Guidelinesfor quality

improvement. International Standard ISO 9004-4. 1994.
Reusable all-glass or metal-and-glass syringes for medical use.Part 1:Dimensions.
International Standard ISO 595-1. 1986.
Reusable all-glass or metal-and-glass syringes for medical use.Part 2:Design, performance
requirements and tests. International StandardISO 595-2. 1987.
Transfusion equipment for medical use. Part 1: Glass transfusionbottles, closures and caps.
International Standard ISO 1135-1. 1987.
Plastics collapsible containers for human blood and blood components.International Standard
ISO 3826. 1993.
Injection containers for injectables and accessories. Part 1: Injection vialsmade of glass
tubing. International Standard ISO 8362-1. 1989.
Injection containers for injectables and accessories. Part 2: Closures forinjection vials.
International Standard ISO 8362-2. 1988.
Injection containers for injectables and accessories. Part 3: Aluminiumcaps for injection
vials. International Standard ISO 8362-3. 1989.155
Injection containers for injectables and accessories. Part 4: Injectionvials made of moulded
glass. International Standard ISO 8362-4. 1989.
Injection containers for injectables and accessories. Part 5: Freezedrying closures for
injection vials. International Standard ISO8362-5.1995.
Injection containers for injectables and accessories. Part 6: Caps madeof aluminiumplastics
combinations for injection vials. InternationalStandard ISO 8362-6. 1992.
Injection containers for injectables and accessories. Part 7: Injectioncaps made of aluminium
plastics combinations without overlappingplastics part. International Standard ISO 8362-7.
1995.
Infusion equipment for medical use. Part 4: Infusion sets for single use,gravity feed.
International Standard ISO 8536-4. 1998.
Infusion equipment for medical use. Part 5: Burette-type infusion sets.International Standard
ISO 8536-5.1992.
Infusion equipment for medical use. Part 6: Freezedrying closures forinfusion bottles.
International Standard ISO 8536-6. 1995.
Infusion equipment for medical use. Part 7: Caps made of aluminiumplastics combinations
for infusion bottles. International Standard ISO8536-7. 1992.

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Sterile single-use syringes, with or without needle, for insulin. Interna-tional Standard ISO
8537. 1991.
Elastomeric parts for aqueous parenteral preparations. InternationalStandard ISO 8871. 1990.
Aluminium caps for transfusion, infusion and injection bottles general requirements and test
methods. International Standard ISO8872. 1988.
Injection equipment for medical use. Part 1: Ampoules for injectables.International Standard
ISO 9187-1. 2000.
Injection equipment for medical use. Part 2: One-point-cut (OPC)ampoules. International
Standard ISO 9187-2.1993.
Dental cartridge syringes. International Standard ISO 9997. 1999.Caps made of aluminium
plastics combinations for infusion bottlesand injection vials requirements and test methods.
InternationalStandard ISO 10985. 1999.
Prefilled syringes. Part 1: Glass cylinders for dental local anaestheticcartridges. International
Standard ISO 11040-1. 1992.156
Prefilled syringes. Part 2: Plungers and discs for dental local anaesthetic cartridges.
International Standard ISO 11040-2. 1994.
Prefilled syringes. Part 3: Aluminium caps for dental local anaestheticcartridges. International
Standard ISO 11040-3. 1993.
Prefilled syringes. Part 4: Glass barrels for injectables. InternationalStandard ISO 11040-4.
1996.
Prefilled syringes. Part 5: Plungers for injectables. International Stan-dard ISO 11040-5.
1996.
Containers and accessories for pharmaceutical preparations. Part 1:Drop-dispensing bottles.
International Standard ISO 11418-1. 1996.
Containers and accessories for pharmaceutical preparations. Part 2:Screw-neck bottles for
syrups. International Standard ISO 11418-2.1996.
Containers and accessories for pharmaceutical preparations. Part 3:Screw-neck bottles (vials)
for solid and liquid dosage forms. International Standard ISO 11418-3. 1996.
Containers and accessories for pharmaceutical preparations. Part 4:Tablet bottles.
International Standard ISO 11418-4. 1996.
Containers and accessories for pharmaceutical preparations. Part 5:Dropper assemblies.
International Standard ISO 11418-5. 1997.
Containers and accessories for pharmaceutical preparations. Part 7:Screw-neck vials made of
glass tubing for liquid dosage forms. International Standard ISO 11418-7. 1998.
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Pen-injectors for medical use. Part 1: Requirements and test methods.International Standard
ISO 11608-1. 2000.
Pen-injectors for medical use. Part 2: Needlesrequirements and testmethods. International
Standard ISO 11608-2. 2000.
Pen-injectors for medical use. Part 3: Finished cartridges requirements and test methods.
International Standard ISO 11608-3.2000.
Pen systems. Part 1: Glass cylinders for pen-injectors for medical use.International Standard
ISO 13926-1. 1998.
Pen systems. Part 2: Plungers and discs for pen-injectors for medicaluse. International
Standard ISO 13926-2. 1999.
Disposable hanging devices for transfusion and infusion bottles requirements and test
methods.International Standard ISO 15010.1998.
A pharmaceutical product should meet above standards before going to a market11.
CONCLUSION
Packaging of pharmaceuticals deals with protection, presentation, convenience, identification
information, and compliance of a product during storage, transportation, display and until the
product is safely consumed. Also increasing demand of market enforced development in
pharmaceutical packaging. The review deals with the advanced techniques in pharmaceutical
packaging like blow- fill- seal, tamper evident and closed vial technology can be used in
development of sterile as well as non- sterile products.
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Francis e-Library, 2005: 1-6.
5. James Swarbick. Encylopedia of Pharmaceutical Technology. Informa Healthcare. Third
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