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www.wjpps.com Vol 3, Issue 5, 2014.

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Jadhav et al. World Journal of Pharmacy and Pharmaceutical Sciences

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.

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,

transportation, display and until the product is safely

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

product safely reaches from producer to consumer. The review mainly

focuses on recent advances in packaging technology and packaging

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

*Correspondence for Author

Dr. G. B. Jadhav

Department of Quality

Assurance, R. G. Sapkal

College of Pharmacy, Anjaneri,

Nashik.


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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 INTEGRITY PURITY

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


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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 Blow-

fill- 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.

ADVANTAGES OF PACKAGING

MINIMUMSIDE-EFFECTS GOOD STABILITY WITH A CLEARLY DEFINED SHELF-LIFE PROFILE


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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.



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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.


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.


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.


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.


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.


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.


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.


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.


Containers and accessories for pharmaceutical preparations. Part 5:Dropper assemblies.


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.


203


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


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


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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