2. CONTENTS AS PER SYLLABUS…
Various materials used,
Factors influencing choice of containers,
Packaging components and types,
Official quality control tests and methods of evaluation,
3. DEFINITION OF PACKAGING
Packaging is the science, art, and technology of enclosing or protecting products for
distribution, storage, sale, and use.
Packaging refers to the process of design, evaluation, and production of packages.
Packaging may also 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.
Packaging is a process by which the pharmaceuticals are
suitably packed so that they should retain their therapeutic
effectiveness from the time of packaging till they are consumed.
4. IMPORTANCE OF PACKAGING
Packaging affects the quality stability and identification of drug
Packaging provide an adequate degree of protection, minimize the
loss of constituents and should not interact physically or
chemically with the contents in a way that will alter their quality to
an extent beyond the limits given in the individual monograph, or
present a risk of toxicity.
Pharmaceutical packaging is the means of providing protection,
presentation, identification, information and convenience to
encourage compliance with a course of therapy.
The requirement of packaging material testing is set according to
specification of regulatory agencies like WHO GMP, USFDA and ICH
5. THE IDEAL CONTAINER OR PACKAGE SHOULD
➢ 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
Particles - protect from particulate contamination.
Microorganisms - protect from microbial contamination.
6. THE IDEAL CONTAINER OR PACKAGE SHOULD
➢ 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.
7. THE IDEAL CONTAINER OR PACKAGE SHOULD
➢ 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.
➢ 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.
8. THE IDEAL CONTAINER OR PACKAGE SHOULD
➢ Must be convenient and easy to use by the patient.
➢ Must be cheap and economical.
➢ Must not react with the content.
➢ Must be biodegradable.
➢ Stable performance over large range of temperatures.
➢ Protect the product from O2, moisture and light.
➢ Protection of the content from adulterations.
➢ Closure characteristics such as opening, sealing, resealing and pouring.
➢ Low cost and availability.
➢ It should non-toxic in nature.
➢ Proper labeling, storing, marketing appeal to sale etc.
9. SELECTION OF PACKAGING MATERIAL
✓ They must protect the preparation from environmental conditions.
✓ They must not be reactive with the product,
✓ They must not impart tastes or odours 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.
✓ They must have reasonable cost in relation to the cost of the product.
10. TYPES OF PACKAGING: PRIMARY PACKAGING
✓ Primary packaging is the material that first envelops the product and holds
✓ This usually is the smallest unit of distribution or use and is the package
which is in direct contact with the contents.
✓ Purpose: 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.
✓ Examples: Ampoules, Vials, Containers, Closures (plastic, metal), Dosing
dropper, Syringe, Strip package, Blister packaging.
11. TYPES OF PACKAGING: SECONDARY PACKAGING
✓ Secondary packaging is outside the primary packaging,
✓ Used to group primary packages together.
✓ Purpose: The secondary packaging mainly provides the additional physical protection
necessary to endure the safe warehousing and for refill packaging.
✓ Example: Paper and boards, Cartons ,Corrugated fibers, Box manufacture.
12. TYPES OF PACKAGING: TERTIARY PACKAGING
✓ Tertiary packaging is used for bulk handling , warehouse storage and transport
✓ The most common form is a palletized unit load that packs tightly into containers.
13. SPECIAL TYPES OF PACKAGING: UNIT-DOSE PACKAGING
✓ This packaging guarantees safer medication by reducing medication errors; it is also
more practical for the patient.
✓ It may be very useful in improving compliance with treatment and may also be useful for
less stable products.
14. SPECIAL TYPES OF PACKAGING: “DEVICE” PACKAGING
✓ Packaging with the aid of an administration device is user-friendly and also improves
✓ This type of packaging permits easier administration by means of devices such as prefilled
syringes, droppers, transdermal delivery systems, pumps and aerosol sprays.
✓ Such devices ensure that the medicinal product is administered correctly and in the right
15. LIST OF PACKAGES FOR STERILE DOSAGE FORMS
✓ All types of parental:
✓ IV infusion (small volume + large volume),
✓ SC injections,
✓ intrathecal injections,
✓ intramuscular injections,
✓ Oral vaccines: tripsules
✓ Ophthalmic product: Drops and ointment
17. USING OF PACKAGING MATERIAL
✓ Glass : Ampule, vials, syringe, SVI, LVI, vaccine storage, dropper
✓ Metals : Vials (primary packaging)
✓ Rubbers : Vials, syringe’s plunger, vaccine closer (primary packaging)
✓ Plastics : Ampule, vials, syringe, SVI, LVI, vaccine storage, dropper, tripsules,
(primary packaging as well as secondary packaging)
✓ Fibrous matter : All types of secondary packaging
✓ Films, Foils/laminates : All types of secondary packaging
18. CONTAINER AND CLOSURES
✓ A container for a Pharmacopoeial article is intended to contain a drug substance or drug
product with which it is, or may be in direct contact.
✓ The closure is a part of the container.
✓ Packaging closures are an important piece of the total packaging solution.
✓ A closure is typically used to seal a container after the initial opening in order to preserve
the product for use at a later time.
✓ Closures also assist in the dispensing of the product.
19. QUALITIES OF GOOD CONTAINER
✓ The container must be neutral towards the material which is stored in it.
✓ The container must not interact physically or chemically with the substance which it holds.
✓ It should help in maintaining the stability of product against the environmental factors
which causes its deterioration.
✓ It should be made of materials which can withstand wear and tear during normal handling.
✓ It should be made of materials which can withstand wear and tear during normal handling.
✓ It should be able to withstand changes in pressure and temperature.
✓ The materials used for making of the container must be non-toxic.
20. COMMON TYPES OF CLOSURES AND USES
✓ CT - Continuous Thread Closures: They pair with a container that has a
continuous spiral protruding on the outside of the finish or neck, as the
closure itself has a thread on the inside of it.
✓ Used in food, household items, pet, health & beauty products. 20
✓ CR or CRCs - Child Resistant Closures: These are typically used for
products that are required by the Consumer Product Safety Commission
to be packaged in child-resistant packaging.
✓ The packaging is significantly difficult for children under five years old to
open within a reasonable amount of time, while not being overly difficult
for a typical adult to use properly.
✓ Used for pharmaceuticals and chemical products.
21. COMMON TYPES OF CLOSURES AND USES
✓ TE - Tamper Evident Closures: These are used when the closure has to provide assurance
that the original product is intact.
✓ Very common in the food, beverage, health and beauty industries.
✓ Provide anti-counterfeiting protection for OTC pharmaceuticals and nutraceuticals.
✓ Dispensing Closures: These are used to control the amount of product that gets
dispensed when used.
✓ Commonly used for food, household, health and beauty products.
✓ Better suited for dry products like spices and fertilizers.
✓ Sprayers and pumps are also types of dispensing closures, though they can
sometimes be in their own closures category as well.
✓ Bar Top / T-Top Closures: Commonly used for spirits and specialty foods.
✓ Top part of their closure can be made of plastic, wood, metal, or glass while the bottom
part is typically natural or synthetic cork.
22. TYPES OF PACKAGING CONTAINERS
✓ Airtight container: A container that is impermeable to solids, liquids and gases under ordinary
conditions of handling, storage and transport. If the container is intended to be opened on more than
once, it must be so designed that it remains airtight after reclosure.
✓ Hermetically Sealed container: A container that is impervious to air or any other gas under
normal conditions of handling, shipment, storage and distribution, e.g. sealed glass ampoule, gas
✓ Light-resistant container: A container that protects the contents from the effects of actinic light by
virtue of the specific properties of the material of which it is made.
✓ Multidose container: A container that holds a quantity of the preparation suitable for two or more
✓ Sealed container: A container closed by fusion of the material of the container.
23. TYPES OF PACKAGING CONTAINERS
✓ Single-dose container: A container that holds a quantity of the preparation intended for total or
partial use as a single administration.
✓ Tamper-evident container: A container fitted with a device or mechanism that reveals irreversibly
whether the container has been opened.
✓ Tightly-closed container: A tightly-closed container protects the contents from contamination by
extraneous liquids, solids or vapours, from loss or deterioration of the article from effervescence,
deliquescence or evaporation under normal conditions of handling, shipment, storage and distribution.
A tightly-closed container must be capable of being tightly re- closed after use.
✓ Well-closed container: A well-closed container protects the contents from extraneous solids and
liquids and from loss of the article under normal conditions of handling, shipment, storage and
26. GLASS CONTAINERS
✓ Preparation of glass:
✓ Glass is composed principally of sand (silica - SiO2), soda-ash (Na2CO3 – sodium carbonate) and
lime-stone (CaCO3-calcium carbonate).
✓ Glass made from pure silica consists of a three-dimensional network of silicon atoms each of
which is surrounded by four oxygen atoms an in this way the tetrahedral are linked together to
produce the network.
✓ Glass prepared from pure silica require very high temperature to fuse, hence soda-ash and lime is
used to reduce the melting point.
27. TYPES OF GLASS
Type of glass Main Constituents Properties Uses
• Borosilicate glass
e.g. Pyrex, Borosil
• SiO2 - 80%
• B2O3 - 12
• Al2O3 - 2%
• Na2O+CaO - 6%
• High m. p. point so can withstand high
• Resistant to chemical substances
• Reduced leaching action
• Laboratory glass
• For injections and for WFI.
• Treated soda-lime
• Made of soda lime glass.
• The surface of which is
treated with acidic gas
like SO2 (i. e. dealkalised)
at elevated temperature
(5000C) and moisture.
• The surface of the glass is fairly
resistant to attack by water for a period
• Sulfur treatment neutralizes alkaline
oxides on surface, thereby rendering the
glass more chemically resistant.
• Used for alkali sensitive
• Infusion fluids, blood &
• Large volume container
• Regular soda-lime
• It contains high concentration of
alkaline oxides and imparts alkalinity to
• Flakes separate easily.
• May crack due to sudden change of
• For all solid dosage forms
(e.g. tablets, powders)
• For oily injections
• Not to be used for aqueous
• Not to be used for alkali-
28. ADVANTAGES OF GLASS CONTAINER
✓ Physical aspect
✓ They are quite strong and rigid.
✓ They are transparent which allows the visual inspection of the contents; especially in ampoules and
✓ They are available in various shapes and sizes. Visually elegant containers attracts the patients.
✓ Borosilicate (Type-I) and Neutral glasses are resistant to heat so they can be readily sterilised by
✓ Glass containers can be easily cleaned without any damage to its surface e.g. scratching or bruising.
✓ Economical aspect
✓ They are cheaper than other packaging materials. 28
29. ADVANTAGES OF GLASS CONTAINER
✓ Chemical aspect
✓ Borosilicate type of glass is chemically inert. Treated soda lime glass has a chemically inert surface.
✓ As the composition of glass may be varied by changing the ratio of various glass constituents the
proper container according to desired qualities can be produced.
✓ They do not deteriorate with age, if provided with proper closures.
✓ Photosensitive drugs may be saved from UV-rays by using amber color glass.
30. DISADVANTAGES OF GLASS CONTAINER
✓ Physical aspect
✓ They are brittle and break easily.
✓ They may crack when subject to sudden changes of temperatures.
✓ They are heavier in comparison to plastic containers.
✓ A transparent glass gives passage to UV-light which may damage the photosensitive
drugs inside the container.
31. DISADVANTAGES OF GLASS CONTAINER
✓ Chemical aspect
✓ Flaking: From simple soda-lime glass the alkali is extracted from the surface of the container and a
silicate rich layer is formed which sometimes gets detached from the surface and can be seen in the
contents in the form of shining plates -known as ‘flakes’ and in the form of needles - they are known as
‘spicules’. This is a serious problem, especially in parenteral preparations.
✓ Weathering: Sometimes moisture is condensed on the surface of glass container which can extract
some weakly bound alkali leaving behind a white deposit of alkali carbonate to remain over there,
further condensation of moisture will lead to the formation of an alkaline solution which will dissolve
some silica resulting in loss of brilliance from the surface of glass -called weathering. To prevent
weathering, the deposited white layer of alkali carbonates should be removed as early as possible by
washing the containers with dilute solution of acid and then washing thoroughly with water. 31
33. POWDER GLASS TEST
✓ From the glass containers, alkaline constituents (oxides of sodium, potassium, calcium,
aluminum, etc.) are leached into purified water under conditions of elevated temperatures.
✓ When the glass is powdered the leaching of alkali can be enhanced in the powdered is critical.
✓ The principle involved in the powdered glass test in estimate the amount of alkali-leached form
the glass powder.
✓ The amount of acid that is necessary to neutralize the released alkali (a specified limit) is
specified in the pharmacopoeia.
✓ The basic analysis is acid-base titration using methyl red indicator.
34. STEPS IN POWDER GLASS TEST
Preparation of specimen of powdered glass test.
36. WATER ATTACK TEST
✓ This test is used only with containers that have been exposed to sulphur dioxide fumes under
controlled humidity conditions.
✓ Such a treatment neutralizes the surface alkali. Now the glass becomes chemically more resistant.
✓ The principle involved in the water attack test is to determine whether the alkali leached form the
surface of a container is within the specified limits or not.
✓ The inner surface is under test entire container (ampoule) has to be used.
✓ The amount of acid that is necessary to neutralize the released alkali from the surface is estimated,
the leaching of alkali is accelerated using elevated temperature for a specified time.
✓ Methyl red indicator is used to determine the end point.
✓ The basic is acid-base titration. 36
43. PLASTICS CONTAINERS: GENERAL PROPERTIES
✓ Plastics are synthetic polymers of high molecular weight.
✓ They are sensitive to heat, and many may melt or soften at or below 1000C. Several plastics can be
autoclaved e.g. nylon, polycarbonate,
✓ polypropylene, high density polyethylene (HDPE) etc.
✓ Plastic containers are light in weight, they are easier to handle.
✓ Mechanically they are almost as strong as metals and, therefore, containers can have thinner walls than glass
✓ They are poor conductors of heat, a disadvantage if the content is to be autoclaved.
✓ Generally, they are resistant to inorganic chemicals but are often attacked by organic chemicals but are often
attacked by organic solvents and oils.
✓ Plastic contain some additives (e.g. antioxidants, lubricants, plasticizers, stabilizers, filler) which may
contaminate the content.
✓ Very few types of plastics completely prevent the entry of water vapour and some are permeable to gases
like oxygen, carbon-di-oxide.
44. TYPE OF PLASTICS
✓ Plastics are classified into two groups according to their behavior when
✓ Thermoplastic type: On heating, they soften to a viscous fluid which
hardens again on cooling. Examples are Polyethylene, polypropylene,
polyvinylchloride, polystyrene, nylon (polyamide), polycarbonate, acrylic
multipolymers, polyethylene terephthalate etc.
✓ Thermosetting type: When heated, they may become flexible but they
do not become liquid; usually their shape is retained right up to the
temperature of decomposition. Due to high degree of cross-linking they
are usually hard and brittle at room temperature. Examples include
phenol-formaldehyde, urea formaldehyde, melamine formaldehyde.
45. ADDITIVES OF PLASTICS
✓ Stabilizer: Side reactions during polymerization may produce a proportion of unsaturated potentially unstable
compounds. Stabilizers are used to stop those side reactions. e.g. octyl tin to stabilize PVC.
✓ Antioxidants: Plastics are vulnerable to oxidation. An anti-oxidants bind with the free radicals and stops the
oxidation reaction. e.g. N,N’-di-b-napthyl-p-phenylene diamine for stabilizing plastics and rubbers.
✓ Pigments: These are used for decorative purpose. They may absorb electro-magnetic radiation in UV region and
thereby reducing photo degradation. For clear plastics organic absorbers such as 4-biphenyl salicylate are used.
✓ Fillers: Used to make the product cheap but in some cases may be essential for correct product performance. e.g.
Bakelite, a phenol-formaldehyde resin, is brown brittle material, quite unsuitable for the manufacture of screw
caps unless mixed with a filler such as wood flour. Examples of fillers: whiting, asbestos and mica.
✓ Plasticizers: Used to reduce Tg of a polymer. They do it by directly reducing the attractive forces between polymer
chains. Ex. PVC.
✓ Other agents: Cross-linked agents, curing agents, activators and accelerators etc. 45
46. DRUG-PLASTIC CONSIDERATION
✓ A packaging 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 separate categories:-
✓ Chemical reaction, and
✓ Alteration in the physical /chemical properties of plastics or products.
47. TESTS ON PLASTIC CONTAINER:
PARENTERAL AND NON-PARENTERAL
✓ Leakage test:
✓ Fill ten containers with water.
✓ Fit with intended closures and keep them inverted at RT for 24 hour.
✓ There are no signs of leakage from any container.
✓ Collapsibility Test:
✓ This test applicable to containers which are to be squeezed in order to remove the
✓ A container by collapsing inwards during use yields at least 90% of its nominal contents
at the required rate of flow at ambient temperature.
48. TESTS ON PLASTIC CONTAINER:
PARENTERAL AND NON-PARENTERAL
✓ Clarity of aqueous extract:
✓ Select unlabeled, unmarked and non-laminated portions from suitable containers, taken at random
sufficient to yield a total area of sample required taking into account the surface area of both sides.
✓ Cut these portions into strips none of which has a total area of more than 20 cm2.
✓ Wash the strips free from extraneous matter by shaking them with at least two separate portions of
distilled water for about 30 seconds in each case, then draining off the water thoroughly.
✓ Transparency test:
✓ Fill five empty containers to their nominal capacity with diluted suspension as described in IP 1966.
✓ 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.
49. TESTS ON PLASTIC CONTAINER:
PARENTERAL AND NON-PARENTERAL
✓ Water vapour permeability test:
✓ Fill five containers with nominal volume of water and heat seal the bottles with an aluminum foil-poly
ethylene laminate or other suitable seal.
✓ Weigh accurately each container and allow to stand (without any overwrap) for 14 days at a relative
humidity of 60±5% and a temperature between 20 and 250C.
✓ Reweigh the containers.
✓ The loss in weight in each container is not more than 0.2%.
50. TESTS ON PLASTIC CONTAINER:
PARENTERAL AND NON-PARENTERAL
✓ BIOLOGICAL TESTS: The USP has provided its procedures for evaluating the toxicity of plastic
materials essentially the tests consist of three phases:
✓ Implantation test: Implanting small pieces of plastic material intramuscularly in rabbits.
✓ Systemic injection test: Injecting eluates using sodium chloride injection, with and without
alcohol intravenously in mice and injecting eluates using poly ethylene glycol 400 and sesame oil
intraperitoneally in mice.
✓ Intracutaneous test: Injecting all four eluates subcutaneously in rabbits. The reaction from test
samples must not be significantly greater than nonreactive control samples.
✓ The closure is normally the most vulnerable and critical component of a container as far as
stability and compatibility with the product is concerned.
✓ Suitable closing of the container is necessary because
✓ It prevents loss of material by spilling or volatilization.
✓ It prevents the deterioration of product from the effects of environment such as moisture, oxygen,
or carbon dioxide.
✓ It avoids contamination of the product from dirt, microorganism or insects.
✓ A closure for a container for an aqueous parenteral preparation or for a sterile powder is a packaging
component which is in direct contact with the drug.
✓ A rubber closure is made of materials obtained by vulcanization (cross-linking) of elastomers with appropriate
✓ The elastomers are produced from natural or synthetic substances by polymerization, polyaddition or
✓ The nature of the principal components and of the various additives such as vulcanisers, accelerators, stabilizing
agents, pigments, etc. depends on the properties required for the finished closure.
✓ Rubber closures are used in a number of formulations and consequently different closures possess different
✓ The closures chosen for use with a particular preparation should be such that the components of the
preparation in contact with the closure are not adsorbed onto the surface of the closure to an extent sufficient to
affect the product adversely. 53
54. TEST FOR RUBBER CLOSURES
✓ 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.
✓ If it exceeds that stated value, the hypodermic needle can be
damaged as a result of undesirable hardness of the closures.
✓ This test is performed on 20 closures.
✓ Each closure is penetrated with hypodermic needle in a piercing
machine five times within a limited area and needle is washed to
transfer any fragment present.
✓ The contents are filtered through colored paper that contrasts with
the rubber and the fragments counted.
✓ On an average there should not be more than three fragments per unit.
55. TEST FOR RUBBER CLOSURES
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 the atmospheric pressure and leave the vials immersed for 30 minutes.
✓ Rinse the outside of the vials.
✓ None of the vials contains any trace of colored solution.
✓ Closures are subjected for sterilization
✓ By Autoclaving at 64-66 C & pressure 0.7kPa
✓ Further testing is carried out by using culture media
56. TEST FOR RUBBER CLOSURES
Preparation of sample solution
✓ Wash closure in 0.2%w/v of anionic surfactant for 5 min.
✓ Rinse 5 times with D.W. and add 200 ml water
✓ Further subjected to autoclave and covering with Aluminum foil.
✓ Allow to cool and separate solution from closure
pH of Aqueous Extract
✓ Take 20ml of sample solution and add 0.1ml of bromothymol blue
✓ Add 0.01M of NaOH till color change from Blue to Yellow. Volume required is measured
✓ Limits: Vol. of NaOH – NMT 0.3 ml If HCL is used –NMT 0.8 M
57. TEST FOR RUBBER CLOSURES
Light Absorption Test
✓ It must be done within 4 hr of preparing sample solution.
✓ It is filtered and its absorbance is measured at 220nm to 360nm.
✓ Blank is done without closure and absorbance must be NMT 2.
Residue on Evaporation
✓ The 50ml of sample solution is evaporated at 1050C.
✓ Residue obtained should be NMT 4mg.