PACKAGING

INTRODUCTION
 Pharmaceutical packaging is the means of providing protection,
presentation, identification, information, and especially
enabling accurate dosing and compliance.
– Spoons, cups for oral dose measurement and delivery.
– Dropper tubes for eye/ear/oral delivery of drops.
– Applicators (e.g. pessaries)
– Dispensing devices, actuators, pre-filled syringes.
– Dose counting and calendar devices.

OBJECTIVES
 Physical protection  Security
 Barrier protection  Convenience
 Containment or  Portion control
agglomeration
PACKAGING TYPES
1. Primary packaging 3. Tertiary packaging
2. Secondary packaging
1. PRIMARY
PACKAGING
 Primary packaging is the material that first envelops the
product and holds it. This usually is the smallest unit of
distribution of use and is the package which is in direct contact
with the contents.
 For example: Unit packs

 Different type of primary packaging includes:

– Ampules – Dosing dropper
– Vials
2. SECONDARY
– Containers PACKAGING
– – Syringe
– – Strip package
– Closures – Blister packaging
 Secondary packaging is outside the primary packaging – perhaps
used to group primary packages together.
– Paper and boards
 Cartons
– Box manufacture
– Corrugated fibers
3. TERTIARY PACKAGING
 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.

TYPES OF PHARMACEUTICAL
PACKAGING MATERIALS
 Materials Use for Packaging
are
– Polycrystalline (metals)
– Polymerization
products (Plastic, glass,
rubber)
– Paper and board.

GLASS TRANSITION OF POLYMERIZATION PRODUCTS

 Tg is the temperature below which hard rigid and brittle solids (glassy
state)
 Glasses are super cooled liquids of high viscosity (1013 Poise)
 It is a brittle transparent material based on the network of oxygen and
silicon items.
CHARACTERISTICS OF PACKAGING MATERIALS
 They must protect the preparation from environmental conditions.
 They must not be reactive with the product.
 They must not impart to the product tastes or odors.
 They must be nontoxic.
 They must be FDA approved.
 They must meet applicable tamper-resistance requirements.
 They must be adaptable to commonly employed high speed packaging
equipment.

SELECTION OF PACKAGING MATERIALS

1. On the facilities available, for example, pressurized dispenser requires
special filling equipment.
2. On the ultimate use of product. The product may be used by skilled
person in hospital or may need to be suitable for use in the home by a
patient.
3. On the physical form of the product. For example, solid, semi-solid,
liquids or gaseous dosage form.
 4. On the route of administration. For example, oral, parenteral, external,
etc.
5. On the stability of the material. For example, moisture, oxygen, carbon
dioxide, light, trace metals, temperature or pressure or fluctuation of
these may have a deleterious effect on the product.
6. On the contents. The product may react with the package such as the
release of alkali from the glass or the corrosion of the metals and in turn
the product is affected.
7. On the cost of the product. Expensive products usually justify
expensive packaging.

FACTORS AFFECTING SELECTION OF PACKAGING MATERIALS

 Mechanical factors
– These include Shock, Compression, Puncture and Vibration.
 Environmental factors
– These include Temperature, Pressure, Moisture, Gases, Light,
Infestation and Contamination

CONTAINERS
 Container is one in which the product is placed.
 A pharmaceutical container is defined as a device that holds the drugs
and is or may be in direct contact with the preparation.

IDEAL REQUIREMENTS OF CONTAINERS

 Must be neutral towards the material which is stored in it.
 Must not interact with the substance which it holds.
 Help in maintaining the stability of the product.
 Withstand wear and tear during normal handling.
 Dose can be drawn from it conveniently.
 Able to withstand changes in pressure and temperature.
 Must be non-toxic.
 Can be labelled easily.
 Pharmaceutically elegant appearance.

TYPES OF
CONTAINER  Light-resistant containers
 Well-closed containers  Air-tight containers
 Single dose containers  Aerosol containers
 Multi dose containers
 MATERIALS USED FOR MAKING CONTAINERS
1. Glass 3. Metal
2. Plastic 4. Paper and board

1. GLASS
INTRODUCTION
 They are transparent and available in various shapes and sizes.
 They can withstand the variation in temperature and pressure during
sterilization.
 They are economical and easily available.
 They can protect the photosensitive medicaments from light during their
storage.
 They are neutral after proper treatment and impermeable to
atmospheric gases and moisture.
 They have good protection power and do not deteriorate with age.
 They can be easily labelled and sealed hermetically or by removable
closures.
MANUFACTURING OF GLASS
COMPOSITION
 Glass is composed of sand, soda ash, limestone and cullet.
 Silicon, aluminum, boron, sodium, potassium, calcium, magnesium,
zinc and barium are generally used in the preparation of glass.
 The sand is almost pure silica, the soda ash is sodium carbonate, and the
limestone is calcium carbonate.
 Cullet is a broken glass that is mixed with the batch and acts as a
fusion agent for the entire mixture.
 The composition of glass varies and is usually adjusted for specific
purposes.
 The most common cations found in pharmaceutical glassware are
sodium, calcium, magnesium, zinc and potassium.
MODIFIERS
 Monovalent metals
 Divalent metals
 Trivalent metals
GIVING SHAPES TO THE CONTAINERS
  Blowing  Casting
 Drawing  Pressing
COLORED
GLASS
 Glass containers for drugs are generally available in clean flint or amber
color.
 The amber coloration results from the addition of iron oxide to the glass.
 For decorative purposes, special colors such as blue, emerald green and
red may be obtained from the glass manufacturer.
 Colored glasses are effective in protecting the content from the effect of
sunlight by screening them.
TYPES OF GLASS
 Type 1: Neutral or Borosilicate glass
– For injectable and laboratory apparatus
 Type 2: Treated Soda lime glass
– For alkali sensitive products, infusion fluids blood and plasma
 Type 3: Regular Soda lime glass
 Type 4: General Purpose Soda lime glass

TYPE I: BOROSILICATE GLASS

 It is least reactive.
 A substantial amount of alkali or earth cations are replaced by boric
oxide.
 This type of glass has higher ingredient like aluminium and zinc and
higher processing costs and is therefore used primarily for more
sensitive pharmaceuticals such as parenteral or blood products e.g.
Ampoules and vials.
TYPE II: TREATED SODA LIME GLASS
 When a glass is stored for several months in damp atmosphere or
with extreme temperature variations, the wetting of surface results in
salts being dissolved out of glass in the form of fine crystals. This is
called
‘BLOOMING OR WEATHERING’. At this stage, these salts can be washed
off with water or acid.
 Commercial soda lime glass is de alkalized or treated to remove surface
alkali to prevent the weathering of empty bottles. This treatment is
known as ‘SULPHUR TREATMENT’.
 SULPHUR TREATMENT involves treating the glass surface with sulfur
 dioxide or ammonium sulfate.
 It also has a high chemical resistance but not as much as type I.
 It is cheaper than type I glass, however, and is acceptable for most
products and aqueous pharmaceuticals with a pH greater than 7.
TYPE III: REGULAR SODA LIME GLASS
 Types III and Type IV glass have similar compositions and distinguished
from each other by their hydrolytic resistance.
 Containers are untreated and made of commercial soda-lime glass of
average or better than average chemical resistance.
 Suitable for non-aqueous parenteral and non-parenteral products.
TYPE IV: NP- GENERAL PURPOSE SODA LIME GLASS
 These have lowest hydrolytic resistance, which can sometimes be seen
as a surface bloom if the glass is stored in damp conditions for prolonged
periods, and is suitable for solid products, some liquids and semi- solids,
but not for parenteral.
ADVANTAGES OF GLASS
 Versatile and attractive.
 Superior protective qualities
 Can be molded into many shapes, sizes and colors of container.
 It is hygienic and suitable for sterilization, it has excellent barrier
properties, it is relatively non-reactive, it can accept a variety of closures,
and glass containers can be used on high speed packaging.
 It can be colored to protect light sensitive materials.
 It can be reused.
 They are neutral after proper treatment.

DISADVANTAGES OF GLASS
 It is fragile  It is harder to dispose
 It is heavy  It is expensive
ADDITIVES OF GLASS
 Mn/Fe for amber color
 Co/Cu for blue color
 Pb to improve clarity
 Alumina- to increase hardness and durability.
 2. PLASTIC
INTRODUCTION
 Plastic packaging systems define a set of packaging materials that are
composed wholly or in substantial portion of plastic materials which
contain or is intended to contain pharmaceutical formulations.
 They are very commonly used as packaging materials for most types of
pharmaceutical dosage forms due to the several advantages they
possess over glass containers.
TYPES OF PLASTIC
 THERMOPLASTIC TYPE: - Tg very low
– This type of plastic gets softened to a viscous fluid on heating and
hardens again on cooling.
 THERMOSETTING TYPE: - Tg very high, crosslinked plastics
– This type of plastic does not gets softened to a viscous fluid on
heating and hardens again on cooling.
COMPOSITION OF PLASTIC
 Plastics are synthetic polymers of high molecular weight.
 Plastic containers for pharmaceutical product are primarily made from
the following polymers:
– polyethylene
– polypropylene
– polyvinyl chloride
– polystyrene and to lesser extent, polyethylene methacrylate and
amino formaldehyde.
PRODUCTION OF PLASTICS
 Synthesis (polymerization)
 Compounding (excipient)
 Molding (fabricated into shape)
– Compression – Extrusion
– Injection
ADDITIVES IN PLASTIC
CONTAINERS
 Stabilizers - to prevent degradation of polymer chain (octyl tin in PVC)
 Antioxidant (retard oxidation)
 Plasticizer - to achieve softness and flexibility (Camphor, castor oil)
 Pigment - for decorative purposes
 Fillers (asbestos, mica)
ADVANTAGE OF PLASTIC
 Light in weight.
 Poor conductor of heat.
 Sufficient mechanical strength.
 Transported easily.
 Unbreakable.
 Good protection power.
 Resistance to inorganic chemicals.

DISADVANTAGE OF PLASTIC
 Permeable to water vapor and atmospheric gases.
 Cannot withstand heat without softening or distorting.
 Absorb chemical substance, Such, preservatives for solution.
 They are relatively expensive.

EVALUATION OF PLASTIC
 Plastic can be evaluated by the following tests
– Leakage test
– Collapsibility test
– Clarity of aqueous extract
– Water vapor permeability test

DRUG PLASTIC INTERACTIONS

 Toxicity  Sorption
 Permeability  Chemical reactivity
 Leaching  Modification
USES AND
PROBLEMS
 LEACHING: A process in which plastic material get dissolved by the
action of liquid dosage form.
 SORPTION: A process by which one substance becomes attached to
another.
 PERMEATION: It is penetration of liquid or gas into the solid.
 CHEMICAL REACTION: Plastic may react with the dosage form i.e. liquid
or semi solid.

3. METALS
 The metals commonly used are aluminum, tin plated steel,
stainless steel, tin and lead.
ADVANTAGE OF METALS
 They are sturdy
 They are impermeable to light, moisture, gas
 They are light in weight as compared to glass containers.
 Labels can be printed directly on to their surface.

DISADVANTAGE OF METALS
 They are expensive.
 They may shed metal particles into pharmaceutical products.
 They are not generally used for extemporaneous dispensing.
 They react with certain chemicals of drug.

METAL CONTAINERS
 Collapsible tubes
 Metal containers for tablets and capsules
 Metal foil

COLLAPSIBLE TUBES METAL

 The collapsible metal tube is an attractive container that permits
controlled amounts to be dispensed easily, with good reclosure,
and adequate protection of the product.
 It is light in weight and unbreakable and lends itself to high speed
automatic filling operations.
 Most commonly used are tin, aluminum and lead.
o TIN
– Tin containers are preferred for food, pharmaceuticals and
any product for which purity is considered.
– Tin is the most chemically inert of all collapsible metal
tubes.
o ALUMINIUM
– Aluminum tubes offer significant savings in product shipping
costs because of their light weight.
– They are attractive in nature
o LEAD
– Lead has the lowest cost of all tube metals and is widely
used for non-food products such as adhesives, inks. paints
and lubricants.
– Lead should never be used alone for anything taken
internally because of the risk lead poison.
 – With internal linings, lead tubes are used for products such
as chloride toothpaste.

4. PAPER AND BOARD

 Both are composed of cellulose obtained by the mechanical
or semi chemical treatment of visit able fibers dried from
various sources like wood, hemp, cotton, etc. in some case
waste and regenerated paper is used.

RUBBER (ELASTOMERS)
Closure in multiple dose vials (insertion of needle and resealing when
needle is withdrawn)
 Natural rubber (latex of rubber tree)
 Synthetic rubber
– Styrene butadiene – Silicon rubber
– Nitrile rubber
SPECIFICATION FOR RUBBER AS PACKAGING MATERIAL
 Force required to penetrate the closure
 Limitation of fragments detached
 Reseal property
 Permeability to oxygen and water.

VULCANIZATION PROCESS
 Vulcanization is a chemical process in which the rubber is heated with
Sulphur accelerator and activator at 140–160°C.
 The process involves the formation of cross-links between long rubber
molecules so as to achieve improved elasticity, resilience, tensile
strength, viscosity, hardness and weather resistance.

CLOSURES
 Closures are the devices by means of which containers can be opened
and closed.
 It prevents loss of material by spilling or volatilization.
 It avoids contamination of the product from dirt, micro-organism or
insects.
 It prevents deterioration of the product from the effect of the
environment such as moisture, oxygen or carbon dioxide.
TYPE OF CLOSURE
 Threaded Screw Cap Crown cap

Lug Cap Roll on closures

MATERIALS USED FOR

CLOSURE  Metal
 Cork  Rubber
 Glass
 Plastic
EVALUATION OF
CLOSURES
 Sterilization test
 Fragmentation test
 Self sealibility test

COMMONLY USED PACKAGES IN PHARMA INDUSTRY

• Jars • Ampoules
• Bottles • Vials
• Collapsible tubes • Blisters
• Sachet • Strips
UNIT PACKS
• Unit packs in which individual dosage are separated from each other are
popular for many types of dosage form.
• It is done through strip packaging.
BLISTER PACKAGING
• Blister packaging is a type of pre-formed plastic packaging used for small
consumer goods.
• The two primary components of a blister packs are the cavity made from
either plastic or aluminum and the lidding made from paper, plastic or
aluminum.
• The cavity contains the product and the lidding seals the product in the
package.
ADVANTAGES OF BLISTER PACKAGING
• Product integrity • Reduced possibility of
• Product protection accidental misuse
• Temper resistance • Patient compliance

Blister
Packaging

Thermo Cold
foaming foaming

Transparent amber Alu-Alu

POLYVINYL CHLORIDE (PVC)
• Very clear, stiff material
• Excellent thermoformability
• Low permeability
• Low cost
• Good chemical resistance
• Thickness of about 10-15mm
POLYVINYLIDENE CHLORIDE (COATED PVC)
• PVDC is the most common coating in blister
packaging because it can reduce the gas and
moisture permeability of PVC blister packages
• Coated PVC films have thickness of 8-10mm
• Coating is applied on one side and usually faces the product
 • Excellent oxygen and moisture barrier properties as compared to normal
PVC.
POLYSTYRENE
• It is perfectly compatible with the thermoforming
• Its high-water vapor permeability makes it unsuitable as a
blister material for pharmaceutical purpose
ALUMINIUM BLISTER FOIL
• Used in cold foaming technique
• Alu-Alu packaging
• Good barrier to moisture, vapor and gases
• 20-25µm thick

PACKAGING LINE
• In pharmaceutical industry packaging is a coordinated process
• All process starting from primary packaging till tertiary packaging done
in a series of process coordinated/ mounted on a single machine
• These machines are called as packaging line.

DEFECTS IN PHARMACEUTICAL PACKAGING

• Lack of heat seal – incomplete heat seal
• De-laminations channel voids and contaminations
• Inclusions of product or foreign materials in the seal area
• Misplaced lids/tops/closures or crimp seals
• Invisible defects/leaks Holes or crack defects in empty vials/ampoules

QUALITY CONTROL OF PACKAGING

• Powdered Glass Test (As per USP):
– Water Attack at 121°C
• Testing of Plastic Container for toxicity
• Leakage test for Plastic Containers
– Water Vapor Permeability
• Test for Plastic Containers for Injectable
• Collapsibility Test for Plastic Containers