CONTAINERS AND CLOSURES FOR

PHARMACEUTICALS – PART 1 Ms. Deepali Temgar,

Deputy General Manager
Corporate Compliance
THIS SLIDE IS ONLY FOR THE CONTENT.
Types, performance, assuring quality of glass;
Types of plastics used,
Drug plastic interactions, biological tests, modification of plastics by drugs;
different types of containers, closures and closure liners;
OVERVIEW
Packaging may be defined as the collection of different components (e.g. bottle, vial,
closure, cap, ampoule, blister) which surround the pharmaceutical product from the time of
production until its use.
Packing is the art and science which involves preparing the articles for transport, storage,
display and use.
Pharmaceutical packaging is the means of providing protection, presentation, identification,
information and convenience to encourage compliance with a course of therapy.
ROLE OF PACKAGING
Protecting the product from the environment and vice versa
 being an effective barrier to light, moisture, oxygen, bacteria, volatiles, etc. as appropriate)
 protection from damage
Providing all necessary information for...
 Identification , preparation if required (e.g. reconstitution, dilution), use of the medicine
including precautions
 Storage and shelf-life of in-use product
 Appropriate disposal of any unused medicine and the packaging itself
Labelling and Product Inserts/Patient Information Leaflets
Enabling accurate dosing and compliance
e.g. Spoons, cups or syringes for oral dose measurement and delivery
Ensuring supply-chain integrity of the medicine
e.g. “Track-and-Trace” systems assuring “chain of custody”, Anti-counterfeiting measures
 WHY PACKAGING
The ideal container or package should:
1. Protect the contents from the following environmental hazards:
• Light - protect the contents from light
• Temperature - be capable of withstanding extremes of temperature.
• Moisture - be capable of withstanding extremes of humidity.
• Atmospheric gases - protect the contents from the effect of atmospheric gases (e.g.
aerial oxidation).
• Particles - protect from particulate contamination.
• Microorganisms - protect from microbial contamination
2. Protects the content from the following mechanical hazards
• Vibration - Usually due to transportation
• Compression - this usually includes pressure applied during stacking.
• Shock - such as impact, drops or rapid retardation.
• Puncture - penetration from sharp objects or during handling operations.
• Abrasion - this may create electrostatic effects.
3. They must not add or permit loss to its contents:
• Protect the contents from both loss and gain of water
• Protect the contents from loss of volatile materials
• Must not shed particles into the contents.
• Must not leach anything to the contents
4. Must have a pharmaceutically elegant appearance:
• In a competitive market the appearance of a package first draws the
attraction of the consumers than its contents.
• Must be easy to label and thus to identify the product.

5. Must be convenient and easy to use by the patient.

6. Must be cheap and economical.
7. Must not react with the content.
8. Must be biodegradable.
GENERAL TERMS
Bulk product : Any product that has completed all the processing stages up to, but not
including, final packaging
Containers
➢A container for pharmaceutical use is an article which holds or is intended to contain and
protect a drug and is or may be in direct contact with it.
➢The closure is a part of the container.
➢The following terms include general requirements for the permeability of containers:
✓Well-closed containers,
✓Tightly closed containers and
✓closed containers.
Well-closed containers must protect the contents from extraneous matter or from loss of
the substance under normal conditions of handling, shipment or storage.
Tightly closed containers must protect the contents from extraneous matter, from loss of
the substance, and from efflorescence, deliquescence or evaporation under normal
conditions of handling, shipment or storage. If the container is intended to be opened on
several occasions, it must be designed to be airtight after re-closure.
Hermetically closed containers must protect the contents from extraneous matter and
from loss of the substance, and be impervious to air or any other gas under normal
conditions of handling, shipment or storage.
labels
All finished drug products should be identified by labelling, as required by the national
legislation, bearing at least the following information:
(a) the name of the drug product;
(b) a list of the active ingredients (if applicable, with the International
Nonproprietary Names (INNs)), showing the amount of 123 each present, and a
statement of the net contents, e.g. number of dosage units, mass or volume;
(c) the batch number assigned by the manufacturer;
(d) the expiry date in an uncoded form;
(e) any special storage conditions or handling precautions that may be necessary;
(f) the directions for use, and any warnings and precautions that may be necessary;
(g) the name and address of the manufacturer or the company or person responsible
for placing the product on the market.
Marketing authorization (product licence, registration certificate) A legal document
issued by the competent drug regulatory authority that establishes the detailed
composition and formulation of the product and the pharmacopoeial or other recognized
specifications of its ingredients and of the final product itself, and includes details of
packaging, information given on the label, product information and shelf-life.

Materials - A term used to denote starting materials, process aids, intermediates, active
pharmaceutical ingredients, packaging and labelling materials.

Packaging material - Any material, including printed material, employed in the packaging
of a pharmaceutical product, excluding any outer packaging used for transportation or
shipment. Primary packaging materials are those that are in direct contact with the
product
Packaging process All operations, including filling and labelling, that a bulk product has
to undergo in order to become a finished product.

Production All operations involved in the preparation of a pharmaceutical product, from

receipt of the starting materials, through processing and packaging, to completion of the
finished product.

Quarantine The status of starting or packaging materials, intermediates, or bulk or

finished products isolated physically or by other effective means while a decision is
awaited on their release, rejection or reprocessing.
OTHER PACKS
Ampoule
A container sealed by fusion and to be opened exclusively by breaking. The contents are
intended for use on one occasion only.
Bag
A container consisting of surfaces, whether or not with a flat bottom, made of flexible
material, closed at the bottom and at the sides by sealing; the top may be closed by fusion of
the material, depending on the intended use.
Blister
A multi-dose container consisting of two layers, of which one is shaped to contain the
individual doses. Strips are excluded.
Strip
A multi-dose container consisting of two layers, usually provided with perforations, suitable
for containing single doses of solid or semi-solid preparations. Blisters are excluded.
Bottle
A container with a more or less pronounced neck and usually a flat bottom.
Cartridge
A container, usually cylindrical, suitable for liquid or solid pharmaceutical dosage forms;
generally for use in a specially designed apparatus (e.g. a prefilled syringe).
Tube
A container for multi-dose semi-solid pharmaceutical forms consisting of collapsible
material; the contents are released via a nozzle by squeezing the package.
Vial
A small container for parenteral medicinal products, with a stopper and over seal; the
contents are removed after piercing the stopper. Both single-dose and multi-dose types
exist.
Gas cylinder
A container, usually cylindrical, suitable for compressed, liquefied or dissolved gas, fitted
with a device to regulate the spontaneous outflow of gas at atmospheric pressure and room
temperature.
Injection needle
A hollow needle with a locking device intended for the administration of liquid
pharmaceutical dosage forms.
Injection syringe
A cylindrical device with a cannula-like nozzle, with or without a fixed needle and a
movable piston, used for the administration, usually parenteral, of an accurately measured
quantity of a liquid pharmaceutical form. The syringe may be prefilled, and can be for
single-dose or multi-dose use.
Pressurized container
A container suitable for compressed, liquefied or dissolved gas fitted with a device that,
after its actuation, produces a controlled spontaneous release of the contents at
atmospheric pressure and room temperature.
Single-dose container
A container for single doses of solid, semi-solid or liquid preparations.
PACKAGING TERMINOLOGY
Immediate (Primary) Pack
 Contains and protects the dosage form so is normally in contact with it.
 It bears appropriate label(s) providing content and usage information.
 Immediate pack components are considered essential to the stability of their contents,
whether or not in contact with them.
Secondary Pack
 A pack component with no product contact but may add protection to that provided by
the immediate pack.
Container Closure System
 The sum of packaging components that together contain and protect the dosage form.
This includes primary packaging components and secondary packaging components, if
the latter are intended to provide additional protection (e.g. light barrier) of the drug
product.
Marketing Pack
 Combination of primary and secondary packaging, labeling, associated components (e.g.,
dosing cups, droppers, spoons), and external packaging (e.g., cartons or shrink wrap).
ASPECTS OF PACKAGING

The aspects of packaging to be considered include:

— the functions of packaging;
— the selection of a packaging material;
— the testing of the material selected;
— filling and assembling;
— sterilization
— storage and stability
 FACTORS INFLUENCING THE CHOICE OF PACK
❖ The product: The physical and chemical characteristics of the drug entity, the excipients, the
formulation, route of deterioration of the product, type of patient (baby, child, teenager, adult,
elderly, infants etc) must be considered while dealing with the pharmaceutical product. Apart from
the properties of drug, package style to attract patient and other legal requirements should also be
considered during selection.
❖ The market: The channel of sale should be considered, i.e. where, when, how and by whom it is to
be used or administered (e.g. doctor, dentist, nurse, patients etc), whether for home trade and/ or
export. The quantity per package and follow up sale must all be carefully considered during package
design and selection.
❖ The distribution system: The distribution system should be carefully monitored, e.g. conventional
wholesale/ retail outlet or direct or selective outlets. Less sophisticated transport systems like
mules, donkeys, camels etc requires additional protection if intermediate storage facilities are non
existent.
❖ Manufacturing facilities: The stability of the manufacturing facilities should be considered due to
new package, increased sale, improvements in Good Manufacturing Practice, revised product, new
product etc.
SELECTION OF PACKING MATERIAL
The materials selected for packaging must have the following characteristics:
• They must protect the preparation from environmental conditions.
• They must not be reactive with the product,
• They must not impart tastes or odors to the products,
• They must be non-toxic,
• They must be FDA (Food & Drug Administration) approved,
• They must meet applicable tamper-resistance requirements
• They must be adaptable to commonly employed high-speed packaging equipment and
• They must have reasonable cost in relation to the cost of the product
 PACKING MATERIAL CATEGORIES
• Primary Packaging:
This is the first packaging envelope which is in touch with the dosage form or equipment
(i.e. bottle, cap, cap liner, label etc).
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.

The main functions of the primary package are to contain and to restrict any chemical,
climatic or biological or occasionally mechanical hazards that may cause or lead to product
deterioration.
Packaging must also function as a means of drug administrations.
PACKING MATERIAL CATEGORIES
•Secondary Packaging:
This is consecutive covering or package which stores pharmaceuticals packages in it for their
grouping.
E.g. Cartons, boxes, etc.

OR
The packaging external to the primary package is known as the secondary packaging.
The secondary packaging mainly provides the additional physical protection necessary to
endure the safe warehousing and for refill packaging.

•Tertiary packaging:
This is to provide bulk handling and shipping of pharmaceuticals from one place to another.
E.g. Containers, barrels, etc.
 GLASS
Glass containers for pharmaceutical use are intended to come into direct contact with
pharmaceutical products.
Glass used for pharmaceutical containers is either borosilicate (neutral) glass or soda-lime-
silica glass.
Borosilicate glass contains significant amounts of boric oxide, aluminium oxide and alkali
and/or alkaline earth oxides.
Glass is also classified as Type I, II or III based on intended use.
MANUFACTURE OF GLASS
The four basic processes used in the production of glass are:
✓ Blowing uses compressed air form the molten glass in the cavity of metal mold.
✓ In drawing , molten glass is pulled through dies or rollers that shape the soft glass.
✓ In pressing mechanical force is used to press the molten glass against the side of a mold.
✓ Casting uses gravity or centrifugal force to cause molten glass to form in the cavity of mold
ADVANTAGES & DISADVANTAGES
ADVANTAGES
• They are hygienic and suitable for sterilization
• They are relatively non reactive ( depending on the grade chosen)
• It can accept a variety of closures
• They can be used on high speed packaging lines
• They are transparent.
• They have good protection power.
• They can be easily labeled.

DISADVANTAGES
• It is relatively heavy
• Glass is fragile so easily broken.
• Release alkali to aqueous preparation
Glass Type
Type I
Composition: Borosilicate Glass
Use: This type of glass has borosilicate structure. It is ideal for containing all injectable preparations with
acid, neutral and alkaline pH. It has good resistance to thermal shocks and can be sterilized before or
after filling. Container of USP type I glass (Neutral borosilicate glass)
Type II
Composition: Soda-Lime-Silica Glass but with a suitable treatment on the inner surface to increase the
hydrolytic resistance
Use: This type of glass is a soda-lime glass which, by means of a special treatment, reaches the hydrolytic
stability of type I glass on its surface layer of 0.1-0.2 um. It is suitable for acidic and neutral parenteral
preparations. Type II glass container can be sterilized before or after filling. Container of USP type II glass
(Treated soda-lime glass)
Type III
Composition: Soda-Lime-Silica Glass
Use: This type of glass has average hydrolytic resistance. It is suitable for containing non-aqueous
injectable preparations and those in powder form. It can also be used for non-parenteral preparations.
Type III glass container should be sterilized by dry heat before filling. Container of USP type III glass (Soda-
lime glass)
QUALITY CONTROL OF GLASS
Glass containers for pharmaceutical use comply with the relevant test or tests for
hydrolytic resistance. When glass containers have non-glass components, the test apply
only to the glass part of the container.
To define the quality of glass containers according to the intended use, one or more of
the following tests are necessary.
Test of hydrolytic resistance are carried out to define the type of glass (I, II or III) and to
control its hydrolytic resistance.
In addition, containers for aqueous parenteral preparations are tested for arsenic release
and coloured glass containers are tested for spectral transmission.
1) CHEMICAL RESISTANT OF GLASS CONTAINERS
A) POWDERED GLASS TEST: It is done to estimate the amount of alkali leached from the
powdered glass which usually happens at the elevated temperatures. When the glass is
powdered, leaching of alkali is enhanced, which can be titrated with 0.02N sulphuric acid using
methyl red as an indicator

Step-1: Preparation of glass specimen: Few containers are rinsed thoroughly with purified water
and dried with stream of clean air. Grind the containers in a mortar to a fine powder and pass
through sieve no.20 and 50.
Step-2: Washing the specimen: 10gm of the above specimen is taken into 250 ml conical flask and
wash it with 30 ml acetone. Repeat the washing, decant the acetone and dried after which it is used
within 48hr.

Procedure: 10gm sample is added with 50ml of high purity water in a 250ml flask. Place it in an
autoclave at 121⁰C±2⁰C for 30min.Cool it under running water. Decant the solution into another
flask, wash again with 15ml high purity water and again decant. Titrate immediately with 0.02N
sulphuric acid using methyl red as an indicator and record the volume.

According to USP Volume 27

Preparation of specimen for powdered glass test
Powdered glass test (according to USP Volume 27)
B) WATER ATTACK TEST: (USP) 76
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 30min then it is cooled and the liquid is
decanted which is titrated with 0.02N sulphuric 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.

Test Container Volume of 0.02 NH2SO4

Powdered glass test Type I 1.0
Type II 8.5
Type III 15.0
Water Attach Test Type II (100 ml or below) 0.07
Type II (above 100ml) 0.02
Water Attack Test
2) HYDROLYTIC RESISTANCE OF GLASS CONTAINERS:
Rinse each container at least 3 times with CO2 free water and fill with the same to
their filling volume. Also fill & Cover the vials and bottles and keep in autoclave. Heat
to 100⁰C for 10min and allow the steam to issue from the vent cork. Rise the temp
from 100⁰C to 121⁰C over 20min. Maintain the temp at 121⁰C to 122⁰C for
60min.Lower the temp from 121⁰C to 100C over 40min venting to prevent vacuum.
Remove the container from autoclave, cool and combine the liquids being examined.
Measure the volume of test solution into a conical flask and titrate with 0.01M HCl
using methyl red as an indicator. Perform blank with water and the difference
between the titration represents the volume of HCl consumed by the test solution.
Nominal capacity of Number of containers to Volume of test solution to
container (ml) be used be used for titration (ml)
5 or less Atleast 10 50.0
6 to 30 At least 5 50.0
More than 30 At least 3 100.0
3) ARSENIC TEST
This test is for glass containers intended for aqueous parenterals. Wash the inner
and outer surface of container with fresh distilled water for 5min.Prep test as
described in the test for hydrolytic resistance for an adequate no. of samples to
produce 50ml.pipette out 10ml solution from combined contents of all ampoules to
the flask. Add 10ml of HNO3 to dryness on the water bath, dry the residue in an
oven at 130⁰C for 30min cool and add 10ml hydrogen molybdate reagent .Swirl to
dissolve and heat under water bath and reflux for 25min. Cool to room temp and
determine the absorbance at 840nm.Do the blank with 10ml hydrogen molybdate.

The absorbance of the test solution should not exceed the absorbance obtained by
repeating the determination using 0.1ml of arsenic standard solution (10ppm) in
place of test soln.
4) THERMAL SHOCK TEST:
Place the samples in upright position in a tray. Immerse the tray into a hot water for
a given time and transfers to cold water bath, temp of both are closely controlled.
Examine cracks or breaks before and after the test. The amount of thermal shock a
bottle can withstand depends on its size, design and glass distribution. Small bottles
withstand a temp differential of 60 to 80⁰C and 1 pint bottle 30 to 40⁰C. A typical
test uses 45C temp difference between hot and cold water.

5) INTERNAL BURSTING PRESSURE TEST:

The most common instrument used is American glass research increment pressure
tester .The test bottle is filled with water and placed inside the test chamber. A
scaling head is applied and the internal pressure automatically raised by a series of
increments each of which is held for a set of time. The bottle can be checked to a
preselected pressure level and the test continues until the container finally bursts.
6) LEAKAGE TEST:  Drug filled container is placed in a container filled with coloured
solution (due to the addition of dye)which is at high pressure compared to the pressure
inside the glass container so that the coloured solution enters the container if any cracks
or any breakage is present.

7) ANNEALING TEST:  The sample is examined by polarized light in either a polariscope or

strain viewer. The strain pattern is compared against standard discs or limit samples.

8) VERTICAL LOAD TEST:  The bottle is placed between a fixed platform & a hydraulic
ramp platform which is gradually raised so that a vertical load is applied. The load is
registered on pressure gauge.

9) AUTOCLAVING (121C for 60 min)  Ability of a filled or empty container to withstand

autoclaving may be checked.
 PLASTICS
According to British standards institutes plastics represents; “ A wide range of solid
composite materials which are largely organic, usually based upon synthetic resins or upon
modified polymers of natural origin and possessing appreciable mechanical strength. At a
suitable stage in their manufacturing, most plastics can be cast, molded or polymerized
directly into shape
Some containers are now being made of plastics; the main use is for bags for parenteral
solutions. Plastic containers have several advantages compared with glass containers:
➢They are unbreakable
➢They are collapsible
➢They are light.
CLASSES OF PLASTICS
There are two classes of plastics, reflecting the behaviour with respect to individual or
repeated exposure to heating and cooling.

 Thermoplastics
Capable of being shaped after initial heating and solidifying by cooling.
Resistant to breakage and cheap to produce and providing the right plastics are chosen
will provide the necessary protection of the product in an attractive containers.
E.g. Polystyrene, polyethylene and polyvinyl chloride.

 Thermosets
They need heat for processing into a permanent shape. During heating such materials
form permanent crosslinks between the linear chains, resulting in solidification and loss
of plastic flow.
E.g. Phenolic, urea and melamine are representative of thermosets.
ADVANTAGES & DISADVANTAGES
ADVANTAGES
• Least expensive than glasses
• Ease of transportation
• No risk of breakage
• Flexible
• Light in weight

DISADVANTAGES
• They are not as chemically inert as Type -I glass.
• They are not as impermeable to gas and vapour as glass.
• They may possess an electrostatic charge which will attract particles.
TYPES OF PLASTIC AND CLASSIFICATION:
Polyethylene Terephthalate sometimes absorbs odours and flavours from foods and drinks
that are stored in them. Items made from this plastic are commonly recycled. PET(E) plastic
is used to make many common household items like beverage bottles, medicine jars, rope,
clothing and carpet fibre.

High-Density Polyethylene products are very safe and are not known to transmit any
chemicals into foods or drinks. HDPE products are commonly recycled. Items made from
this plastic include containers for milk, motor oil, shampoos and conditioners, soap bottles,
detergents, and bleaches. It is NEVER safe to reuse an HDPE bottle as a food or drink
container if it didn’t originally contain food or drink.

Polyvinyl Chloride is sometimes recycled. PVC is used for all kinds of pipes and tiles, but is
most commonly found in plumbing pipes. This kind of plastic should not come in contact with
food items as it can be harmful if ingested.
Low-Density Polyethylene is sometimes recycled. It is a very healthy plastic that tends to be
both durable and flexible. Items such as cling-film, sandwich bags, squeezable bottles, and
plastic grocery bags are made from LDPE.

Polypropylene is occasionally recycled. PP is strong and can usually withstand higher

temperatures. It is used to make lunch boxes, margarine containers, yogurt pots, syrup
bottles, prescription bottles. Plastic bottle caps are often made from PP.

Polystyrene is commonly recycled, but is difficult to do. Items such as disposable coffee
cups, plastic food boxes, plastic cutlery and packing foam are made from PS.

Code 7 is used to designate miscellaneous types of plastic not defined by the other six
codes. Polycarbonate and Polylactide are included in this category. These types of plastics
are difficult to recycle. Polycarbonate (PC) is used in baby bottles, compact discs,
and medical storage containers.
QUALITY CONTROL TESTS FOR PLASTICS:
1) LEAKAGE TEST:  Fill 10 containers with water, fit with intended closures and
keep them inverted at room temperature for 24hr.The test is said to be passed if
there is no signs of leakage from any container.

Leakage test for plastic containers (non-injectables & injectables 1996 IP):

Fill 10 plastic containers with water and fit the closure

Keep them inverted at room temperature for 24 hrs

No sign of leakage should be there from any container

2) COLLAPSIBILITY TEST:  This test is applicable to the containers which are to be
squeezed for removing the contents. A container by collapsing inward during use,
yield at least 90% of its normal contents at the required rate of flow at ambient
temperature.
3) WATER PERMEABILITY TEST FOR PLASTIC CONTAINERS (INJECTABLE
PREPARATIONS IP 1996)
4) CLARITY OF AQUEOUS EXTRACT: Select unlabelled, unmarked and non laminated
portions from suitable containers, taken at random. Cut these portions into strips, none of
which has a total surface area of 20sq.cm.Wash the strips free from extraneous matter by
shaking them with at least two separate portions of distilled water for about 30sec. In each
case and drain off the water thoroughly.
Thus processed sample is taken in to the flask, previously cleaned with chromic acid
mixtures and rinsed with several portions of distilled water and added 250ml dist water.
Cover the flask and autoclave at 121⁰C for 30min.Carry out the blank determination using
250ml dist water. Cool and examine the extract, it should be colourless and free from
turbidity.
5) TRANSPARENCY TEST:
Standard suspension preparation: 1gm hydrazine sulphate in 100ml water and set aside
for 6hr. Take 25ml of this solution and add 25ml of 10%w/v hexamine and stand for 24hr.
Test solution preparation: Sample is prepared by 16fold dilution of the standard
suspension. Fill 5 containers cloudiness detectable when compared to water filled
containers. Absorbance is measured at 640nm and the range is within 0.37 and 0.43.
6) BIOLOGICAL TESTS:
A) Systemic Injection Test:
 Test animal – Albino Mice
 Inject each of 5 mice in test group with sample or blank observe the animals immediately, again
after 4hr & then at 24, 48, 72hrs.
 If none of animals shows significant greater biological reactivity than the blank the sample meets
the requirements.
 Limit- If abnormal behavior such as Convulsion or Prostration occurs or if body weight loss is
greater than 2g, the sample does not meet the requirements.

B) Intra Cutaneous Test:

 Test animal- Rabbit
 Examine the sites of for any tissue reaction like erythema, oedema, neuosis at 24, 48, 72 hours
after injection.
 Limit- difference between the scores of sample and blank should be lesser than 1.0.

C) Eye Irritation Test On Rabbits:

Test animal - albino rabbits
Limit- Sample extract shows no significant irritant response during the observation period with blank
extract
 DRUG PLASTIC INTERACTION
The term interaction encompasses the sum of all mass transports from the package into
the product as well as mass transport in the opposite direction. The mass transfers, often
coupled with chemical reactions, lead to quality, Q, changes in the product and packaging
material.
A packaging system must protect the drug without altering the composition of the product
until the last dose is removed.
Drug-plastic considerations have been divided into five categories:
1. Permeation
2. Leaching
3. Sorption
4. Chemical reaction
5. Alteration
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.

Leaching:
• 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.
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…

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.

Modification:
• 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.
• Example oils have a softening effect on polyethylene, hydrocarbons attack polyethylene & PVC
TYPES OF CONTAINERS
•Primary containers including fillers, absorbents, and desiccants
•Secondary functional (e.g, fibre drums, HDPE bottles for products which are
immediately packaged with LDPE bag etc).
•Secondary non functional
•Accessories such as measuring cap
TYPES OF CONTAINERS - BOTTLES
Glass
 Type 1: borosilicate, most inert and preferred for solutions to be autoclaved
 Type 2: treated soda lime, more susceptible to leaching than type 1 glass.
Useful for solutions buffered to maintain pH below 7
 Type 3: traditional soda lime glass. Has more leachable oxides than type 2
glass. Mainly used for dry products (solids)
TYPES OF CONTAINERS – BOTTLES
HDPE bottle
 (-CH2 –CH2 -) n or copolymer with other olefins
 in general considered highly protective, common in pharma
 has good safety profile
 has stronger intermolecular forces and tensile strength than lower-density PE
 permeability also depends on thickness
 semi permeable for liquid preparations
 naturally translucent
PET (Polyethylene Terephthalate or Polyester) bottle
 consists of polymerized units of the monomer ethylene terephthalate
 usually for liquid preparations
 has good gas and fair moisture barrier
 has good safety profile
TYPES OF CONTAINERS – BOTTLES
Polypropylene (PP) is used primarily for jars and closures and provides a rigid
package with excellent moisture barrier.
Closures
 polypropylene screw /CRC caps
 inner seal-eg Inductions seal/heat sealed
 aluminium cap
Fillers, absorbents and moisture adsorbents
 absorbent Cotton
 rayon fibres
 silica gel desiccant (efficient at high relative humidities) or molecular sieve
(efficient at low relative humidities)
TYPES OF CONTAINERS – BAGS
LDPE bag
 as primary container for bulk packs which is further placed in HDPE/PE bottles
 as primary container for bulk product or intermediates
 as primary container for API and excipients, which is further placed in Alu, fiber
or steel drum
 considered safe
 less protective than HDPE and PET
Triple laminated LDPE/PET/Al bag
 three layers 'sandwiched', LDPE film as inner layer
 Protection from oxygen, water vapor, UV
 Protection from other contaminants, e.g. oils, acid, alkalines
TYPES OF CONTAINERS – THERMOFORM BLISTER PACKS
TYPES OF CONTAINERS – COLD FORM BLISTER PACKS
TYPES OF CONTAINERS – TROPICALISED BLISTER PACKS
TYPES OF CONTAINERS – BLISTER AND STRIPS

Blisters and strips

 Alu/Alu
 Al/PVC/PE/Aclar
 Al/PVC/PVDC
 Aluminim/PVC
 in general safe
 CLOSURES
A closure is the part of the package which prevent the contents from escaping and
allow no substance to enter the container.

Closures are available in five basic designs:

1. Screw on, threaded or lug
2. Crimp on(crowns)
3. Press on(snap)
4. Roll on and
5. Friction
Threaded screw cap:
• When a screw cap is applied, its threads engaged with the corresponding threads
molded on the neck of the bottle.
• A liner in the cap, pressed against the opening of the container, seals the product in
the container and provide the resistance to chemical and physical reaction with the
product.
• The screw cap is commonly made of metal or plastics. The metal is usually tin plate
or aluminium and in plastic is thermoplastic and thermosetting material.
Lug cap:
• The lug cap is similar to the threaded screw cap and operates on the same principle.
• It is simply an interrupted thread on the glass finish, instead of a continuous thread.
• Unlike the threaded closure, it requires only a quarter turn.
• The lug cap is used for both normal atmosphere pressure and vacuum pressure
closing.
Crown caps:
• This style cap is commonly used as a crimped
closure for beverage bottles.

Roll-on closures
• The aluminum roll on cap can be seal securely, opened easily and resealed effectively.
• Resealable, non resalable and pilfer proof types of roll on closures are available for use
on glass or plastic bottles.
Pilfer proof closures
• It is similar to roll on closure but has a greater skirt length.
• This additional length extends below the threaded portion and fastened to the basic cap
by the series of narrow bridges.
• When the closure is removed the extra portion remains in the space on neck of the
container, this indicates that the package has been opened
CLOSURE LINERS
A liner may be defined as any material that inserted in a cap to effect a seal between
the closure and the container.

It is of two types:
1. Homogeneous liner 
• These are one piece liners available as disk or a ring of rubber or plastic.
• It can be withstand high temperature sterilization.

2. Heterogeneous liners 
• These are composed of layers of different materials chosen for specific
requirements.
• It consists of facing and backing. Facing is in contact with product and backing
provides questioning effect.
FACTORS IN SELECTING LINER
• Chemical inertness − should be chemically inert
• Appearance, thickness etc.
• Gas and water-vapour transmission rates − should be low.
• Torque require to remove the cap − should be optimum.
• heat resistance − e.g. during autoclaving should be thermostable.
• Shelf-life − should not change their shape during storage.
• Economics − should be cheap
RUBBERS
RUBBERS (Elastomers):
• Excellent material for forming seals, used to form closures such as bungs for vials or in
similar applications such as gaskets in aerosol cans.

Categories of Rubbers:
1) Natural rubbers;
• Suitable for multiple use closures for injectable products as rubber reseals after multiple
insertion of needle.
• Disadvantages are;
i. It doesn't well tolerate multiple autoclaving becoming brittle and leads to relative degree
of extractable material in presence of additives.
ii. Risk of product absorbing on or in to a rubber.
iii. It has certain degree of moisture & gas permeation
2) Synthetic rubber:
• Have fewer additives and thus fewer extractable and tends to experience less
sorption of product ingredients
• Are less suitable for repeated insertions of needle because they tend to
fragment or core pushing small particles of the rubber in to the product.
• E.g. Silicone, butyl, bromobutyl, chlorobutyl etc.
• Silicone is least reactive but it does experience permeability to moisture and gas.

Softer rubbers experience less coring and reseal better, harder rubbers are easier
to process on high speed packaging lines
TYPES OF RUBBER
1. BUTYL RUBBER - These are copolymers of isobutylene with 1-3% of isoprene or
butadiene.
Advantages:-
• After vulcanization butyl rubber possesses virtually no double bond, consequently
they are most resistant to aging and chemical attack.
• Permeability to water vapour and air is very low.
• Water absorption is very low.
• They are relatively cheaper compared to other synthetic rubbers.  Disadvantages
• Slow decomposition takes place above 1300C.
• Oil and solvent resistance is not very good.

2. NITRILE RUBBER
Advantages: • Oil resistant due to polar nitrile group. • Heat resistant.
Disadvantage • Absorption of bactericide and leaching of extractives are considerable
3. CHLOROPRENE RUBBERS (NEOPRENE) These are polymers of 1:4 chloprene.
Advantages
• Due to the presence of −Cl group close to the double bond so the bond is resistant
to oxidation hence these rubbers age well.
• This rubber is more polar hence oil resistant.
• Heat stability is good (upto 1500C).
• Water absorption and permeability are less than for natural rubbers.

4. SILICONE RUBBERS
Advantages
• Heat resistance (upto 2500C).
• Extremely low absorption and permeability of water.
• Excellent aging characteristics due to their saturated chemical structures.
• Poor tensile strength.
Disadvantages • They are very expensive.
Thank You