PACKAGING OF

PHARMACEUTICALS
Presented By: Ms. Pratibha Arote
[M.Pharm-1st Year (QAT-101)]
Guided By: Ms. Ujjwala Desai

PES MODERN COLLEGE OF PHARMACY, NIGDI. PUNE-044.

 CONTENTS
 INTRODUCTION
 PHARMACEUTICAL PACKAGING
 IDEAL REQUIREMENTS OF PHARMACEUTICAL
PACKAGING MATERIALS
 CRITERIA FOR THE SELECTION OF PACKAGING
MATERIALS
 FUNCTIONS OF PHARMACEUTICAL PACKAGING
 TYPES OF PACKAGING SYSTEM
 PACKAGING MATERIALS & CLOSURES
 QUALITY CONTROL OF CONTAINERS
 QUALITY CONTROL OF CLOSURES
 RECENT PACKAGING TECHNOLOGIES
 INTRODUCTION
 The process by which the pharmaceuticals are suitably placed
so that they should retain their therapeutic effectiveness from
the time of their packaging till they are consumed is termed
as packaging.
 Packaging must provide protection against environmental
condition such as physical, chemical and biological hazards
and it must be economical.
 Role of pharmaceutical packaging is to provide life saving
drugs, surgical devices, blood and blood products,
nutraceuticals, powders, liquid dosage forms, solid and
semisolid dosage forms.
 PHARMACEUTICAL PACKAGING

 The combination of components necessary to contain,

preserve, protect & deliver a safe, efficacious drug product,
such that at any time point before expiration date of the drug
product, a safe & efficacious dosage form is available is
called as Pharmaceutical Packaging.
 IDEAL REQUIREMENTS OF
PHARMACEUTICAL PACKAGING
MATERIALS
 Protect the preparation from environmental conditions.
 Non-reactive with the product and so does not alter the
identity of the product
 Does not impart tastes or odours to the product
 Nontoxic
 FDA approved
 Protect the dosage form from damage or breakage
 Adaptable to commonly employed high-speed packaging
equipments.
CRITERIA FOR THE SELECTION OF
PACKAGING MATERIALS
 Stability
 Compatibility with the contents
 Strength of container and the degree of protection required
 Moisture-proofness
 Resistance to corrosion by Acids or Alkalis
 Protection against salt
 Resistance to microorganisms, insects and rodents
 Resistance to differences in temperature
 Protection against light and fire
 Convenience of the packaging for the physician, pharmacist
and finally the patient (size, weight, method of opening/re-
closing)
FUNCTIONS OF PHARMACEUTICAL
PACKAGING

 Containment - The containment of the product is the most

fundamental function of packaging for medicinal products.
 Protection - The packaging must protect the product against
all adverse external influences that may affect its quality or
potency.
 Presentation and information - Packaging is also an
essential source of information on medicinal products.
 Identification - The printed packs serves the function of
providing both identity and information.
 Convenience - The convenience is associated with product
use or administration.
 TYPES OF PACKAGING SYSTEM
1.PRIMARY PACKAGING:
 This is the first packaging envelope which is in touch with the
dosage form or equipment.
 The packaging needs to be such that there is no interaction
with the drug and will provide proper containment of
pharmaceuticals.
 E.g. Blister packages, Strip packages, etc.
 Blister packaging - Blister packaging is commonly known as
unit-dose packaging. Blister packs are low-cost packaging
that is tamper-evident and provides good protection.
 Strip Packaging - Strip packaging is also a unit dose
packaging. These are usually made of aluminum & increases
the shelf-life of the product with individual protection.

 Vials - These are small, cylindrical glass/plastic containers

usually used to store liquid, powdered and sometimes solid
medicines.
 Ampoules - Ampoules are sealed vials made out of
glass/plastic used for storage or liquid or solid medicines.

 Syringes, containers and sachet packaging are also used as

primary packaging.
2.SECONDARY PACKAGING:
 The secondary and tertiary packaging has the function to
protect the primary packaging while storage and transit.
 The secondary packaging is usually also utilized to convey
important information about the drug.
 E.g. Cartons, Boxes, etc.

3.TERTIARY PACKAGING:
 This is to provide bulk handling and shipping of
pharmaceuticals from one place to another.
 The secondary and tertiary packaging has the function to
protect the primary packaging while storage and transit.
 Tertiary level of packaging is usually master carton.
 E.g. Containers, barrels, etc.
 TYPES OF PACKAGING SYSTEM

 GLASS

 PLASTIC

 METALS

 PAPER AND BOARD

 RUBBER

 COTTON
 GLASS CONTAINERS

 Advantages:
 Superior protective qualities
 Economical
 Readily available in a wide variety of sizes & shapes
 Essentially chemically inert, impermeable, strong and rigid
 Has FDA clearance
 Provides an excellent barrier against every element except
light with a proper closure system. Colored glass, especially
amber, can give protection against light.
 Disadvantages:
 1. Fragility
 2. Heavy Weight

 TYPES OF GLASS
 Type I – Borosilicate Glass
 Type II – Treated Soda-Lime Glass
 Type III – Regular Soda-Lime Glass
 Type NP – General Purpose Soda-Lime Glass
 Type I: Borosilicate Glass

 Highly resistant glass.

 It is more chemically inert than the soda-lime glass.

 It is used to contain strong acids & alkalies as well as all

types of solvents.

 The addition of approx 6% boron to form type I glass reduces

the leaching action.
 Type II: Treated Soda-Lime Glass

 Type II containers are made of commercial soda-lime glass

that has been de-alkalized or treated to remove surface alkali.
The de-alkalizing process is known as “sulfur treatment”.

 Thus sulfur treatment neutralizes the alkaline oxides on the

surface & thus rendering the glass more chemically resistant.
 Type III – Regular Soda-Lime Glass

 Containers are untreated & made up of commercial soda-lime

glass of average or better-than-average chemical resistance.

 Type NP – General Purpose Soda-Lime Glass

 Containers made up of soda-lime glass are supplied for non-

parenteral products, those intended for oral or topical use.
 PLASTIC CONTAINERS

 Advantages:

 Ease of manufacturing

 Available in various types of quality

 Extremely resistant to breakage

 Polymers used for the production of Plastics:

 COMMONLY USED POLYMERS

 Polyethylene
 Polypropylene
 Polyvinyl chloride (PVC)
 Polystyrene

 LESS COMMONLY USED POLYMERS

 Polymethyl methacrylate
 Polyethylene terephthalate
 Polytrifluoroethylene
 Aminoformaldehydes
 Limitations of Plastic Materials:

1. PERMEATION

2. LEACHING

3. SORPTION

4. CHEMICAL REACTIVITY

5. MODIFICATION
 I. PERMEATION

 The transmission of gases, vapors or liquids from the

surrounding environment into the plastic container is known
as “Permeation”.

 Permeation of water vapor & oxygen through the plastic wall

into the dosage form can be problematic if the drug is
sensitive to hydrolysis and/or oxidation.

 An increase in temperature, increases permeability of gases.

 Permeation may also affect the shelf-life of a drug.

 II. LEACHING

 Release of a constituent from the plastic material of the

container into the formulation is known as “leaching”.

 For example: Particular Dyes which are used as Coloring

Agents may migrate into a product, contaminates the product
and may cause a toxic effect.
 III. SORPTION

 The Process of removal of one or more of the constituents

from the formulation by the packaging material are referred
to as “Sorption”.

 Becomes a serious problem particularly for dosage forms that

contain drug.

 May significantly affect the therapeutic efficacy of the

formulation containing highly potent drug.
 IV. CHEMICAL REACTIVITY

 Certain ingredients used in plastic container manufacturing

may chemically react with one or more components of a drug
product.

 These chemically incompatible substances may also alter the

appearance of the plastic or formulation.
 V. MODIFICATION

 The physical or chemical alteration of the packaging material

by the drug product is called “modification”.

 Permeation, sorption or leaching may also alter the properties

of the plastic container.

 For example: Oils have a softening effect on polyethylene.

 Plastic Packaging Alternatives
 Plastics is one of the biggest challenges the world is facing right
now. Most exciting innovations in plastic replacement are:
1. Plant-based plastics
2. Mushroom Packaging
3. Seaweed Packaging
4. Recycled cardboard and paper
5. Organic Fabrics
6. Corn starch Packaging
7. Milk plastic
 The Maharashtra Govt. announced that, stores can use
plastic bags above 50 microns of thickness.
 The thickness of the plastic bags determines its strength.
 Single-use plastic ban:
 Single-use plastic items including plastic bags, spoons, cups, straws
and bottles were banned . Government aims to completely eliminate
the use of single-use plastic by 2022.
 India generates about 9.4 million tonnes of plastic waste each year
and with no effective disposal method, the plastic waste ends up the
roadsides, in landfills and water bodies.
 Plastic waste management is a global concern.
 Globally, around 90 percent of the plastic produced is discarded as
waste. So far, more than 60 countries have banned single-use
plastic.
 Single-use plastic items:
 The single-use plastic ban is expected to cover six single-use plastic
items initially including plastic bags, straws, cups, plates, small
bottles and certain types of sachets.
 The ban will cover manufacturing, usage and import of such items.
 The campaign is a part of the central government’s ongoing Swatch
Bharat Mission.
 Single-use plastic alternatives:

 The industry is aiming to produce packaging material that is

recyclable with the use of high viscosity polymer.
 For the packaging of milk, the industry is looking to
manufacture milk pouches from polyester filament yarn
(PFY).
 The yarn is recyclable and can be used 45-50 times.
 The pouches and bags could be sent back by the customers to
their milk suppliers.
 METAL CONTAINERS

 Aluminum & Stainless Steel are the metals of choice for

both primary & secondary pharmaceutical packaging.

 Form excellent tamper-evident containers.

 Metals are strong, impermeable to gases & shatterproof.

 They are ideal packaging material for pressurized containers.

PACKAGE TYPE FORMULATION

Strip, Blister Tablets, Capsules

Collapsible Tubes Ointments, Creams, Gels &

Other Semisolids

Cans Aerosols, Inhalers, Sprays etc.

 PAPER & BOARD

 The paper-based materials are the important part of

pharmaceutical packaging.

 Paper-based materials include: Labels, Cartons, Bags, etc.

 The Applications as well as Advantages of Cartons include:

- Increases display area
- Provides physical protection especially to items like metal
collapsible tubes.
 RUBBER BASED COMPONENTS

 Mostly used to make stoppers and bulbs for dropper

assemblies.

 Examples of rubber for pharmaceutical products include:

1. Natural Rubber
2. Neoprene Rubber
3. Nitrile Rubber
4. Butyl Rubber
5. Chlorobutyl Rubber
6. Bromobutyl Rubber
7. Silicone Rubber
 COTTON
 PACKAGE TYPE:

 Wadding: In solid preparations to absorb moisture etc.

 As Desiccant: To prevent absorption of moisture particularly

by tablets & capsules from environment.
 QUALITY CONTROL OF
CONTAINERS
A.GLASS CONTAINERS
 USP and IP provides two tests to determine chemical
resistance of glass containers:

1.Powdered Glass Test:

 This test is made to know the amount of alkali leached from
the glass powder.
 The amount of acid that is necessary to neutralize the released
alkali is specified in the pharmacopoeia.
 The basic analysis is acid-base titration using methyl red
indicator.
 Sample containers are rinsed with purified water and dried.

Containers are grinded in a mortar to a fine powder and passed through

sieve no. 20 and 50.

10mg of sample is washed with acetone and dried.

50ml of purified water is added to the dried sample and autoclaved at

121oC for 30 min & cooled and decanted.

Decanted liquid is titrated with 0.02N H2SO4 using methyl red

indicator.
2.Water Attack Test:
 This is only for treated soda lime glass containers under the
controlled humidity conditions which neutralize the surface
alkali and glass will become chemically more resistant.
 Principle involved is whether the alkali leached or not from
the surface of the container.
 PROCEDURE:
 Rinse thoroughly with high purity water.
 Fill each container to 90% of its overflow capacity with water
and is autoclaved at 121⁰C for 30 min.
 Then it is cooled and the liquid is decanted which is titrated
with 0.02N sulfuric acid using methyl red as an indicator.
 The volume of sulfuric acid consumed is the measure of the
amount of alkaline oxides present in the glass containers.
B. PLASTIC CONTAINERS

 Leakage Test:
 Fill 10 containers with water.
 Fit with intended closures and keep them inverted at room
temperature for 24 hours.
 There are no signs of leakage from any container.

 Collapsibility Test:
 This test applicable to the containers which are to be
squeezed in order to remove the contents.
 A container by collapsing inwards during use yields at least
90% of its nominal contents at the required rate of flow at
ambient temperature.
 Water vapor permeability Test:
 Fill five containers with nominal volume of water and heat
seal the bottles with an aluminum foil.
 Weigh accurately each container and allow to stand for 14
days at relative humidity of 60±5% and temperature between
20 and 25°C.
 Reweigh the containers. The loss in weight in each container
is NMT 0.2%.

 Transparency Test:
 Fill five empty containers to their nominal capacity with
diluted suspension.
 The cloudiness of the diluted suspension in each container is
detectable when viewed through the containers as compared
with a container of the same type filled with water.
QUALITY CONTROL OF CLOSURES

 Materials used for closures: Cork, Glass, Plastic, Metal, and

rubber
 Penetrability test:
 This is measured to check the force required to make a
hypodermic needle penetrate easily through the closure.
 It is measured by using the piercing machine.
 The piercing force must not exceed a stated value.

 Fragmentation test:
 This test is made on 20 closures.
 Each closure is penetrated with hypodermic needle in a
piercing machine 5 times within limited area and needle is
washed to transfer any fragment present.
 The contents are filtered through coloured paper that
contrasts with the rubber and the fragments counted.
 On an average there should NMT 3 fragments per unit.

 Self-sealability test:
 Applicable to multidose containers.
 Fill 10 vials with water & close them with prepared closures
and secure with a cap.
 For each closure use a new hypodermic needle and pierce 10
times each time at different site.
 Immerse the vials upright in methylene blue(0.1%) solution
and reduce external pressure for 10 minutes.
 Restore atmospheric pressure and leave the vials immersed
for 30 min.
 Rinse the outside of the vials. None of the vials contain any
trace of coloured solution.
 Compatibility test:
 This test is performed to check the compatibility of the rubber
closures with different types of substances.
 Since it is necessary to ensure that there is no interaction
between the contents of the bottle and the closure.

 Light Absorption Test:

 Filter solution A through membrane filter.
 Measure the light absorbance of filtrate in the range 220 to
360 nm using a blank solution.
 The absorbance is NMT 2.
 RECENT PACKAGING
TECHNOLOGIES
 BLOW-FILL-SEAL TECHNOLOGY

 Aseptic blow-fill-seal (BFS) technology is the process by

which plastic containers are formed, filled with sterile filtered
product and sealed in an uninterrupted sequence of operations
within the controlled sterile environment of a single machine.

 The blow-fill-seal process is a robust, advanced aseptic

processing technology, recognized by worldwide regulatory
authorities for its inherent operational advantages over
conventional aseptic production.
 Blow-fill-seal systems offer a unique combination of
flexibility in packaging design, low operating cost and a
high degree of sterility assurance.

 The machines require a minimum number of operating

personnel and have a relatively small space requirement.

 Blow-fill-seal process

 Container moulding

 Container filling

 Container sealing
 Container moulding
 Thermoplastic is continuously extruded in a tubular shape
[Figure 1a]. When the tube reaches the correct length, the
mold closes and the parison is cut [Figure 1b].
 The bottom of the parison is pinched closed and the top is
held in place with a set of holding jaws. The mold is then
transferred to a position under the filling station.

Figure 1: Blow-Fill-Seal process

 Container filling

 The nozzle assembly lowers into the parison until the nozzles
form a seal with the neck of the mold [Figure 1c].

 Container formation is completed by applying a vacuum on

the mold-side of the container and blowing sterile filtered air
into the interior of the container.
 Container sealing
 Following completion of the filling process, the top of the
container remains semi-molten.
 Separate seal molds close to form the top and hermetically
seal the container [Figure 1d].
 The mold opens and the container is then conveyed out of the
machine [Figure 1e].

o The cycle is then repeated to produce another filled container.

The filled containers are tested and checked to ensure that
they meet the very strict specifications laid down for such
products.
o The duration of the complete cycle is between 10-18 seconds,
depending on the container design and the amount of liquid to
be filled.
 ADVANTAGES OF BFS TECHNOLOGY

 BFS technology reduces personnel intervention making it a

more robust method for the aseptic preparation of sterile
pharmaceuticals.
 Cleaning and sterilization of prefabricated containers and
closures is not required. A clean, sterile container is made
within the BFS machine as it is required for filling.
 The cost of material transport, storage and inventory control
is reduced.
 Validation requirements are reduced.
 The code numbers and variable data such as batch number
and expiry date can be molded into the container itself rather
than being added at a subsequent stage.
 The operation of BFS machines is less labor intensive than
conventional aseptic filling.
 PREFILLED SYRINGES
 The use of prefilled syringes is a modern way to apply
parenteral drugs.
 The benefits are convenience and ease of handling, as well as
advantages in safety and a reduction of drug overfill.
 The currently existing market of prefilled syringes is in the
range of US$1-2 billion.
 The growth rate is to be expected to remain at a high level of
more than 10% annually.
 In the future, the pharmaceutical and biotech industries will
ask for prefillable drug delivery systems for valuable potent
drugs.
 Particularly, for biologicals the parenteral application will
remain the most important route of application.
 Prefilled syringes in the US market have been growing at a
rate of 20% per year for at least five years.
 The primary driving factors behind the growth of prefilled
syringes includes:
 Ease of administration; more convenient for healthcare
professionals and end users; easier for home use; easier in
emergency situations.
 Better dose accuracy.
 Increased assurance of sterility.
 Better use of controlled drugs such as narcotics.
 Lower injection costs- less preparation, fewer materials, easy
storage and disposal.
 Removal of preservatives from vaccine formulations.
 Today, prefills can be introduced at any point during a
product's lifecycle to make it more desirable.
 Switching from vials to prefilled syringes, syringes to a nasal
spray or a self injection system, prefills can work easily for
products in development.

Figure 2: BD Hypak PhysiolisTM glass prefilled syringe

(reproduced with permission from BD)
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