CONTACT OF PACKAGING

COMPONENTS LIKE PVC

,ALUMINUM FOILS

By: Qurat-ul-ain
PhD scholar
University of the punjab
 INTRODUCTION:
Pharmaceutical packaging can be defined as the economical means of
providing presentation, protection, identification , information,
containment, convenience ,compliance , integrity and stability of the product.

o The selection of a package therefore begins with a

determination of the products physical and chemical
characteristics, its protective needs, and its marketing
requirements.
The materials selected must have following
characteristics:
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.

Must be non toxic.

They must be FDA approved.

They must meet applicable tamper resistance requirements.

They must be adaptable to commonly employed high-speed packaging

equipment
 MATERIALS USED FOR MAKING OF CONTAINERS:

GLASS
Type I-borosilicate glass
Type II-treated soda lime glass
Type-III regular soda lime glass
Type NP-general purpose soda lime glass

e.g.bottles,vials,ampules,syringes,i.v containers, aerosol containers.

PLASTIC-
Plastic containers for pharmaceutical products are primarily made from
the following polymers
polyethylene
polypropylene
poly vinyl chloride
polystyrene
polymethyl methacrylate
amino formaldehyde
poly amides
e.g.bottlespouches,tapes,tubes,aerosolcontainers,laminates.
RUBBER-
e.g. closures, caps,vialswrapers,plungers.

METALS
Tin:
Aluminum
Lead
e.g. collapsabletubes,foils,needles,aerosol containers

PAPER OR CARD BOARD

e.g. secondary packaging
labels,inserts,displayunits,pouches,laminates,cartons,
carrogated boxes,foils,paper drums
 POLYVINYL CHLORIDE (PVC ):
PVC is a PLASTIC

Plastics are synthetic polymers of high molecular weight.

Plastics as packaging have proved useful for a number of reasons, including the
ease with which they can be formed, their high quality and the freedom to design.

Plastic containers are extremely resistant to breakage and offer safety consumers.

PVC can be produced with crystal clarity, provide a fairly good oxygen barrier, and
have greater stiffness.

PVC can be softened with plasticizers. Various stabilizers, antioxidants,

lubricants, or colorants may be incorporated.

Polyvinyl chloride is seldom used in its purest form.

PVC is an inexpensive, tough, clear material that is relatively easy to

manufacture.
 PVC must not be overheated because it starts to degrade at 280F, and
the degradation products are extremely corrosive.

Polyvinyl chloride yellows when exposed to heat or ultraviolet light,

unless a stabilizer is included.

From the standpoint of clarity, the best stabilizers are the tin
compounds, but the majority cannot be used for food or drug products.

Dioctyl-tin mer-captoacetate and maleate compounds have been

approved by the FDA, but these have a slight odor, which is noticeable in
freshly blown bottles.

Polyvinyl chloride is an excellent barrier for oil, both volatile and fixed
alcohols, and petroleum solvents.

It retains odor and flavors quite well and is a good barrier for oxygen.

Rigid polyvinyl chloride is a fairly good barrier for moisture and gases in
general, but plasticizers reduce these properties. Polyvinyl chloride is not
affected by acids or alkalies except for some oxidizing acids.
 DRUG-PVC CONSIDERATIONS
A packaging system must protect the drug without altering the
composition of the product until the last dose is removed.

Drug-PVC considerations are as follows

1. Leaching
2. Sorption
3. Alteration/Modification

Other Drug Plastic considerations are as follows:

1. Permeation
2. Chemical reaction
 Leaching
(Release of di(2-ethylhexyl)phtalate from polyvinylchloride bags)
Leaching refers to the drug solution extracting one or more components
from the container or device material into the solution, which is then
delivered into the patient.
Some plastic containers have one or more ingredients added to stabilize it,
these may leach into the drug product.
Problems may arise with plastics when coloring agents are added in small
quantities to the formula.
Particular dyes may migrate into the parental solution and cause a toxic
effect.

The most commonly described leaching occurs with the plasticizer

diethylhexyl phathalate (DEHP) leached from polyvinyl chloride
(PVC) plastic by drugs that contain a surfactant in their formulation.

The oily DEHP (which makes PVC soft and pliable) is extracted by the
detergent action of the surfactant and is subsequently delivered to the
patient.
PVC may contain up to >40% of plasticisers mainly di-isononyl
phthalates (DINPs) such as diethylhexyl phthalate (DEHP) which can
migrate to the solution .

Since plasticisers are lipophilic their extraction from the polymer is

favoured by lipophilic solutions such as non-aqueous solvents, lipid
emulsions (liposomes) or solutions containing emulsifying agents such as
polysorbates.

Among non-aqueous solvents ethanol, propylene glycol and PEG at

concentrations up to 25% were unable to extract DEHP from PVC
containers .

On the other hand polysorbate 80 was able to leach DEHP into the
solution in contact with PVC bags.
Moreover, plasticiser can cause unexpected instability of drugs
formulated in non-aqueous solutions.

In one study, a taxol formulation consisting of paclitaxel in 50%

polyoxyethylated castor oil and 50% dehydrated ethanol was added to
glass bottles, PVC infusion bags containing 5% dextrose or 0.9%
NaCl and stored for 12-24 hours at 20-23C .

Solutions stored in PVC became hazier than solutions stored in glass

containers.

DEHP was found in solutions stored in PVC but not in solutions stored in
glass

Thus, paclitaxel solutions should be stored in glass containers

This recommendation should be applied to other non-aqueous

formulations of anticancer drugs such as etoposide, docetaxel and
liposomal suspensions
Observed toxicity of DEHP to different
organ systems
Organ Effect Species
Tubular atrophy and
degeneration, Histological
damage to the testes in
Testis offspring Rat
Suppressed or delayed
Ovaries ovulation, Rat
Human
Lungs Respiratory distress neonate
Decrease in heart rate & Blood
Heart Pressure Rat
Reduction in creatinine
Kidneys clearance ( Rat
Fetus Fetal death Mouse
Liver reduction in liver function Monkey
 Sorption
This process involves the removable of constituents from the drug
product by the packaging material.

The therapeutic efficacy of the product may be reduced due to sorption.

Sorption may change the chemical structure, Ph., solvent system,

concentration of active ingredients and temperature etc
The majority of studies concerning the compatibility of cytotoxic
drug solutions with infusion bags and sets have investigated polyvinyl
chloride (PVC) .In all studies, PVC appeared to lead to the most
sorption.
Other Drugs having demonstrated problems include
isosorbide dinitrate, thiopental sodium,benzodiazepines and
phenothiazines
Interactions between drugs and polyvinyl chloride
infusion bags.
Kowaluk EA,Roberts MS,Blackburn HD,Polack AE.

Forty-six injectable drug products, many of which are administered by i.v.

infusion, were studied for loss from aqueous solutions stored in polyvinyl
chloride infusion bags for various periods of time.
The polyvinyl bags were stored in the dark at room temperature for up to three
months. Drugs stored in glass vials served as controls.
The solutions were assayed spectrophotometrically at regular intervals.
The effects of drug concentration and pH on the loss of drug from solution
were studied.
Five of the drug products-clomethiazole edisylate, diazepam, hydralazine
hydrochloride, thiopental sodium, and warfarin sodium-were found to be lost to a
substantial extent after one week.
For all drugs studied, the effects of the initial concentration on drug loss
varied.

The main physico-chemical determinants controlling drug sorption

appeared to be the extent of ionization and the lipid solubility of the drug.
For most of the drugs studied, minimal losses from the aqueous solutions
were observed over short periods of storage time.

Disappearance was slow and time dependent, indicating a diffusion-

controlled sorption process.

The losses of clomethiazole edisylate, thiopental sodium, and diazepam

may be clinically important.
 Modification/ Alteration
The physical and chemical alteration of the packaging material by
the drug product is called modification.

Some solvent systems found to be considerable changes in the

mechanical properties of the plastics.

For example oils have a softening effect on polyethylene,

hydrocarbons attack polyethylene and PVC.
 Permeation
It is the transmission of gases, vapors or liquids through plastic
packaging material.
Permeation of water vapor and oxygen through plastic wall into the
drug is a major problem is the dosage form is sensitive to hydrolysis and
oxidation.
The volatile ingredients might change when stored in plastic
containers and the taste of the medicinal products may change for the
same reason of permeation.

Chemical reactivity
Certain ingredients in plastic formulations may react chemically
with one or more components of the drug product.
Even in micro quantities if incompatibility occurs may alter the
appearance of the plastic or the drug product.
 PVC products
Wrapping film,
Trays and boxes,
Bottles and jars,
Blister packaging,
crown cork
colostomy bags,
catheters,
urine bags,
infusion set
and blood bags.
 ALUMINUM FOIL

Aluminum foil is a solid sheet of aluminum, or of an appropriate

aluminum alloy, rolled very thin, varying from a minimum thickness
of about 0.00017 in. to a maximum of about 0.0059 in.

Considering the advantage of aluminum foil in preventing

exposure to light, oxygen, moisture, odors, flavors and
specifically bacteria; the pharmaceutical industry
uses aluminum foil extensively and regularly for
packaging of different medicines such as tablets and
capsules etc. They also form the seal under the bottle
top for several bottled medicinal mixtures in syrups or
bundled pill bottles.
 Benefits of Aluminum Foil as a
Packaging Material
Excellent impermeability to water vapor and gases.
Extends shelf life.
Uses less storage space.
Generates less waste than many other packaging
materials.
Used as the barrier component in flexible cans.
Acts as a barrier to oxygen, light, and odor.
Nontoxic and hygienic.
Greaseproof and non-absorptive to liquids.
The aluminum packaging foil can be coated for
protection, decoration, or heat sealing.
Aluminium foil provides the best option for assured
protection from light, e.g.
Suitable blister pack option (foil/foil)
Foil pouches for drug/device combinations
Foil covered infusion bags
Ease of use:To adults, alufoil presents no problems of product
accessibility, even to elderly people. Blister packaging in Peel-push
formats with laminated lidding can be created if child security is a
consideration.
Mechanical properties :A flexible, thin material which can be cut,
formed, embossed, coated, printed or laminated without difficulty..
Environmental acceptability: As with all forms of aluminium
packaging, alufoil makes a positive contribution to our environment
by protecting products and so reducing waste of materials and
energy. Once used, the aluminium in household waste can be
recycled.
Hygiene and safety : Aluminium foil can be supplied in an aseptic
condition, it supports no microorganisms, is safe in contact with
most chemical preparations (or can be suitably coated), contains no
substances of danger to health.
Resistance of aluminum foil to chemical attacks
depends upon the specific compound or agent, but it has
excellent and good compatibility with most products.

Aluminum has high resistance to most fats, petroleum

greases, and organic solvents.

Intermittent contact with water generally has no visible

effect on aluminum .

However, standing water in the presence of certain salts

and caustics can be corrosive. For example, some
hygroscopic products packaged in aluminum foil may
cause some reaction, particularly if the product contains
salt, or salt and some mild organic acid.

In these or any other applications which may subject the

aluminum to mild attack, coating or lamination protection
is employed on the foil surface next to the product.
In general, such food products as candies, milk,
unsalted meats, butter and margarine are compatible
with bare aluminum. They also greatly benefit from its
opacity, which retards deterioration from exposure to
light. Similarly, many drug and cosmetic products are
compatible with aluminum foil and also must be
protected from light.

Aluminum resists mildly acidic products better than it

does mild alkaline compounds, such as soaps and
detergents. While use with the stronger concentrations
of mineral acids is not recommended without proper
protection because of possible severe corrosion.
Some Products made by PVC & Aluminum foils

BLISTER PACKAGE

STRIP PACKAGE

BUBBLE PACK

SEALED TUBES

SACHETS & POUCHES

COLLAPSIBLE TUBES

HEAT SEALED MEMBERANES & CLOSURES

 BLISTER PACKAGE
Alufoil is particularly suitable for blister packs because of its range of
mechanical properties.
It can also be combined with other materials like paper or plastics. Blister
packs are tamper-evident and can be designed to be child-proof or to
provide more secure access.
Most blister packs consist of a preformed plastic tray with an aluminium
foil closure manufactured to facilitate the necessary push-through
characteristic.
A recent development is the all-aluminium blister pack. The cold-formed
trays are filled with the medicine which adopt the shape of the individual
alufoil compartment.
All-aluminium packs are also used for diagnostic products, ointments, and
light sensitive formulations where total barrier performance is required.
As product counterfeiting has become an increasingly serious issue,
holographic effects are now being used on more and more alufoil blister
packs.
 STRIP PACKAGE
A strip package is a form of unit dose packaging that is commonly used for
the packaging of tablets and capsule.
Strip packs can be produced entirely from aluminium or in combination with
paper or plastics, all of which are printable.
A key requirement is the ability to tear open easily. Alufoils malleability and
deadfold characteristic are important in these applications, allowing the metal to
closely match the shape of the tablet. Strip packs provide economical high
barrier performance and can be filled at high speeds on sterile filling lines
The product is dropped into the pocket formed prior to forming the final set
of seals.

A continuous strip of packets is formed in general.

The strip of packets is cut into desired number of packets.
Different packaging materials used are:
paper/polyethylene/foil/PVC.
BUBBLE PACK

A bubble can be made usually by sandwiching the product between a

thermo formable, extensible or heat shrinkable plastic film and a rigid
backing material.

The product is dropped into pocket which is then sealed with heat
sealed coated paper board.
 SEALED TUBES
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 these are made of aluminum.

Extruded plastic tubes are widely used for products that are
compactable and limited protection of plastic.


Alufoil is frequently used as a key component in tube laminates.

Apart from providing excellent barrier performance to protect
sensitive creams, alufoil offers the advantage of deadfold.
So a tube made with alufoil laminate can be designed not to
spring back when squeezed, which can draw ambient air and
contamination back into the tube.

Tubes with holographic or other optical effects are available. In

addition to decorative design opportunities, these surface
finishes can be used as valuable tools against product
counterfeiting.

 Sachets and pouches

The sensitive nature of most pharmaceutical preparations

demands that the packaging provides a perfect barrier to moisture
and often to light.

Alufoil laminated sachets provide packaging solutions for many

products, whether in powder, cream or liquid form. Large alufoil
pouches are also used to store, transport and dispense sterile fluids
used in hospital treatments.

Alufoil sachets keep the product in good condition over long

periods. They withstand rigorous burst tests and are convenient and
economical to transport.

Printed designs, colour coding and anti-counterfeiting finishes are

available.
 Heat sealed membranes and closures

Many medicines are supplied in glass, plastic or metal containers.

Alufoil, laminated with paper or plastic, is frequently used as a

heat-sealed membrane hermetically closing the container, usually
under a plastic screw cap.

The localised heat needed to affect the sealing process is

generated by an electrical induction process after the screw caps
are applied on the filling and capping line.

The resulting alufoil membrane provides excellent barrier

properties preventing moisture or gas transmission as well as
tamper evidence. Safety information can be printed on the alufoil
seal if required.
Thank
you