MODULE: PHARMACEUTICAL SCIENCES & THE

PRACTICE OF PHARMACY

CHAPTER : PACKAGING

SEMESTER: ONE

Date of session: 16/11/24 Kenza Mansouri

Contents:

❖ Introduction
❖ The pharmaceutical pack
❖ Packaging materials
❖ Packaging and regulatory bodies
❖ Designing packaging for safe medicine use
INTRODUCTION:

❖ Packaging of medicines is crucial to their use.

❖ Without the packaging, dispensing and – for many medicines – administration would be almost
impossible.

❖ Packaging contains, presents, protects and preserves the medicine, in addition to providing
identification, information, tamper evidence, convenience and compliance during storage,
distribution, display and use.

❖ Packaging enables a medicine's requirements of efficacy, safety, uniformity, reproducibility,

integrity, purity and stability to be maintained throughout its shelf life.
❖ Furthermore, some pharmaceutical packaging is essential for the medicine's use, i.e. the pack is
the delivery device. E.g. pressurized metered-dose inhalers, eye drops and transdermal patches.

❖ The role of packaging is expanding.

❖ It is seen as a key component to combat the increasing incidence of drug counterfeiting, which
occurs even in countries where the supply chains are trustworthy.

❖ For example, the European Union’s Falsified Medicines Directive calls for the placement of a
unique identifier (a 2D data matrix code and human readable information) and an antitampering
device on the outer packaging of certain medicines in order to fight medicine falsifications.
❖ Visual examination of the packaging and spectroscopy techniques, e.g. infrared spectroscopy, can
also help medicine authentication.

❖ Packaging is also increasingly being used to facilitate medicine administration by health care
practitioners and by patients (e.g. by the use of prefilled syringes).

❖ As for other goods, pharmaceutical packaging is a visual communication tool and is being used to
brand and promote products to the consumer, so much so that pharmaceutical companies
sometimes get in trouble with regulators.

❖ Packaging that reminds patients to take their medicines and which tracks patient adherence will
become more important in the future to reduce the costs of nonadherence with drug therapy.
THE PHARMACEUTICAL PACK:

❖ The primary pack (also referred to as a container-closure system, e.g. a bottle and screw cap)
contains the drug product and is in direct contact with it.

❖ The primary pack may also contain auxiliary packaging components such as a cotton
pharmaceutical coil (a filling material used in bottles of tablets/capsules to prevent breakage of
the tablets/capsules during shipment) or a desiccant sachet.

❖ The secondary pack (e.g. a carton box for a glass bottle) contains the primary pack, as well as
associated components, such as a dosing spoon or a medicine dropper, and information leaflets.

❖ The tertiary packaging (e.g. a cardboard outer box) contains multiple secondary packs, facilitates
handling and transport and prevents damage associated with handling, transport and storage.
1. Primary packs:

❖ The wide range of pharmaceutical products, such as solid powders, granules, tablets, capsules,
semisolids (e.g. creams, ointments, gels) and liquids (e.g. solutions, suspensions, emulsions),
some of which are sterile, obviously requires a great diversity, both in primary pack design and in
packaging materials.

❖ The latter include paper, glass, plastics, rubbers, and metal or combination materials such as
laminates.

❖ Examples of primary packs include blister packs, strip packs, pouches, sachets, bottles, ampoules,
vials, bags, tubes and prefilled syringes.
❖ The primary pack may be a multiple-unit pack and contain many units (e.g. a bottle containing
many tablets) or a single-unit pack and contain a single unit (e.g. blister pack, sachet).

❖ Multiple-unit packs may be more economical in terms of material; for example, one bottle
containing 1 month’s supply of tablets for one patient, or a multidose vial of vaccines for
administration to many patients.

❖ However, multidose containers rely on the user’s practice, which may be deficient, for instance,
changing the needle but reusing the same syringe when the contents of a multidose vial are used
for multiple patients, which can lead to infection outbreaks.

❖ In addition, in a multiple-unit container, the remaining doses in the container are exposed to the
environment every time the container is opened, which can lead to contamination of the
remaining product.
❖ Single-unit containers (also referred to as unit-dose packaging (UDP)) offer many advantages, such
as protection of a dose from the environment until use, as the container is typically opened
immediately before administration. This offers greater product stability and assurance of sterility.

❖ They can also be used to package preservative-free preparations for people who are sensitive to
the antimicrobial preservatives used in multidose presentations.

❖ In addition, as fewer steps are required to prepare a dose for a patient (e.g. for a prefilled syringe
compared with a multidose vial), single-dose containers can reduce the incidence of errors such
as the withdrawal of an incorrect dose, and hence improve patient safety.

❖ Unit-dose packaging also reduces the unintentional exposure of children to medicines. (e.g. the
increased use of unit-dose packaging for combination buprenorphine/naloxone products was
followed by considerable reduction in the rate of paediatric emergency department visits)
Examples of primary packaging:

1 blister packaging, 2 strip packaging, 3 sachet, 4 pouch for a suppository, 5 glass bottle for solid powder for dispersion, 6 glass bottle for liquid preparations, 7 glass
vial for parenteral preparations, 8 glass ampoules, 9 plastic bag for intravenous liquids, 10 metal and plastic in a pressurized metered-dose inhaler (pMDI), 11 metal
canister, 12 plastic eye drop bottle, 13 prefilled syringe for injections and 14 metal ointment tube.
2. Packaging for product stability:

❖ The primary pack must ensure product stability.

❖ It must be compatible with the product, and take nothing out of the product and add nothing to
it.

❖ Sorption (absorption or adsorption) of the drug or other excipients, such as preservatives, into the
container would reduce product potency and stability, whilst chemicals leaching out of the
container and into the product could induce drug degradation.

❖ Solvent loss from a product can also occur if the container is permeable, which could result in
drug and excipient precipitation.
❖ The pack must protect the product against atmospheric factors, such as extremes of temperature,
light, moisture, oxygen, carbon dioxide and particulates (e.g. dust, dirt), as well as biological
hazards, such as microorganisms, insects and rodents.

❖ Drug molecules can undergo chemical reactions triggered by light, heat, moisture or atmospheric
gases, such as oxygen. E.g. :

• Heat can degrade a drug

• Light can provide the energy necessary for a drug isomer to change its configuration.
• Oxygen can cause drug degradation via oxidation.
• Carbon dioxide can dissolve in the water in unbuffered aqueous products and lower their
pH by forming carbonic acid.
• Moisture can cause drug degradation via hydrolysis.
❖ Moisture ingress into a product can also cause dilution of liquid products and wetting of solid
products and can create an aqueous environment which may support microbial growth.

❖ Protection of a medicine against these hazards is achieved by the judicious use of the appropriate
packaging materials and the inclusion of substances which can remove the hazard.

❖ For example, opaque or amber-coloured containers reduce exposure to light.

❖ Containers which are produced from fairly impermeable materials, such as glass, minimize the
escape of solvent from the product and the entrance of moisture and gases.

❖ Desiccants (e.g. silica gel, bentonite, calcium chloride, calcium oxide and molecular sieves) and
oxygen absorbers (such as iron oxide, StabilOx and PharmaKeep) may also be used.
❖ These are contained within sachets or canisters that are placed inside containers (e.g. integrated
within the container closures).
❖ The absorbers may also be integrated within the container walls (e.g. in Oxy-Guard barrier
bottles).

❖ A combination of an impermeable container and a moisture/oxygen absorber sachet may also be

used, the impermeable container protecting against degradation that could arise from ingress of
moisture/oxygen from the atmosphere into the container and the sachet absorbing any
moisture/oxygen present in the headspace (the air in a container above its contents).
❖ Products that are heat-sensitive need to be kept within a narrow temperature range from the
point of manufacture to the point of use.

❖ The cold chain is therefore crucial to ensure the product is effective when used.

❖ However, the cold chain cannot always be guaranteed, for example when the electricity supply is
sporadic (as it is in many countries) or when someone fails to store the product correctly. In such
cases, the incorrectly stored medicines are potentially degraded and hence wasted.

❖ To reduce wastage, temperature monitors may be attached to containers to record their exposure
to heat. E.g., the vaccine vial monitor is a heat-sensitive label that is placed on vaccine vials.
The monitor changes colour as a function of temperature and time, allowing health care workers to
determine, at a glance, if the vaccine in a vial is suitable for use.
❖ Secondary and tertiary packaging also contributes to protection against atmospheric factors to
some extent (e.g. against light).

❖ However, their major role is to provide protection against mechanical hazards during handling and
storage, such as shock (e.g. when dropped), compression, vibration, abrasion and puncture.
3. Packaging for tamper evidence, child resistance and access by older people:

❖ The primary pack must be tamper evident to improve the product’s security from pilferage and
deliberate contamination, thereby safeguarding the product's legitimate user.
❖ Examples of tamper-evident (TE) approaches include TE bands incorporated into bottle caps and
TE shrink bands applied to the bottle neck and cap.

❖ Ideally, packs would be completely tamper-proof, although this is probably impossible to achieve
against determined attempts.
❖ Child-resistant packaging of medicines, introduced to reduce the accidental poisoning of children
by medicines, has prevented thousands of poisonings, and may have saved many lives.
❖ The aim of child-resistant packaging is to make it difficult for children to open containers and
access the medicine, while ensuring that adults can still open and close the packaging easily.

❖ However, easy access to the medicine by adults is not always the case. Older people, who are
more likely to have impaired vision, hand strength and dexterity, often have difficulties opening
medicine packaging.
❖ Such difficulties accessing medicines can reduce medication adherence and lead to poor disease
control.
❖ Strategies to overcome the difficulties with opening medicine packs include asking someone else,
using tools such as scissors, pliers or a screw-cap opener, transferring the medicines to another
container or not reclosing the container fully between administrations.
❖ The latter may compromise the product’s stability, as well as increase the possibility of children
accessing the medicine.

❖ Pharmacists and pharmacy staff can play a significant role in helping older patients take their
medicines by questioning patients and carers, and offering solutions and packaging that are more
senior-friendly.
4. Closures:

❖ A closure is a device (e.g. stopper, lid, top or cap) which is used to close a container and is an
integral part of the pack.

❖ The word pack therefore covers both the container and the closure.

❖ Without the latter, the functions of the pack, such as containment, presentation, protection and
convenience, cannot be fulfilled.

❖ Like the container, the closure must be inert, compatible with the contents and protect the latter
against environmental hazards, such as oxygen, light and moisture.

❖ Certain closures must also maintain sterility (e.g. in multiuse vials for parenteral products).
❖ A good seal between the container and the closure prevents anything from leaking out of or
gaining access into the pack, and is obtained by a snug fit between the inner face of the closure
and the external face of the container.
❖ Resilient liners inside the closure are sometimes used to achieve a snug fit, although many plastic
closures are internally moulded to achieve a good seal and are liner-free.

❖ The closure has to be user-friendly, allow easy opening by legitimate consumers and be easy to
reclose (for multiunit packs), as well as being child resistant and tamper evident.
❖ Closures may also include dispensing devices (e.g. a pump on bottles containing creams).
❖ The outer surface of the closure may be ribbed to allow good grip when it is being opened by
twisting.
❖ Pharmaceutical closures are mostly made of plastic (thermosets and thermoplastics), although
metal is also used (e.g. on parenteral vials).

❖ The word closure does not always refer to a stopper-type device.

❖ Metal tubes have two closures: a cap at one end, whilst the other end of the tube is sealed by
folding and crimping.

❖ Flexible packaging, such as pouches, sachets and blister packs, does not contain a closure as
previously defined.

❖ It is instead sealed by heat and/or pressure, or with adhesives, and is not reclosable.
Packaging materials:

❖ Once the properties and functions of the desired packaging have been defined, the primary
packaging material can be selected, taking into account the dosage form, the route of
administration, product stability, any need for sterilization and for visual inspection of the
packaged medicine, patient adherence and convenience, aesthetics, cost, marketing,
environmental friendliness, etc.

❖ Liquids, which are in constant intimate contact with the primary pack, as opposed to solids such
as tablets and capsules, require greater quality from a pack so that they ‘take nothing out of the
product and add nothing to it’.

❖ Injectable liquids require even greater quality from the pack compared with oral liquids, to
maintain sterility and freedom from other possible contaminants, such as extraneous particulates.
❖ Packaging for medicines which are terminally sterilized in their final packs needs to be made from
materials that can withstand the sterilization procedure.

❖ Semisolid products need to be able to be dispensed from the container, under slight pressure (e.g.
squeezing of a tube).

❖ The packaging material is obviously very important.

❖ Glass, metal and plastic are the materials most commonly used in primary packs.
Comparison of glass,
metal and plastic as a
function of packaging
requirements:
Glass:

❖ Glass, believed to have been first discovered around 3000 BC in the East Mediterranean and
which has been used for thousands of years, is widely used for packaging pharmaceuticals
because of its excellent barrier properties, relative inertness and compatibility with
pharmaceuticals.

❖ Its many advantages and it has traditionally been the gold standard in pharmaceutical packaging.

❖ Primarily consisting of silicon dioxide (silica), glass is produced by the heating together of various
inorganic substances to form a molten mass, and then rapid cooling of the latter, which solidifies
in a noncrystalline state.
❖ Sand (or more correctly silicon dioxide, which is the main constituent of sand), limestone (calcium
carbonate) and soda ash (sodium carbonate) are heated together to very high temperatures in a
furnace. The ingredients melt and gradually react and form a homogeneous molten mass.

❖ The latter is then converted into glass containers by one of two basic methods: blow moulding or
tubular glass fabrication.

❖ Blow moulding, the older method, is when a ‘gob’ (a small piece of highly viscous molten glass) of
glass is moulded into a container.

❖ The second method involves conversion of the homogeneous molten glass mass into tubing as it
moves out of the furnace. The tubing is cut to defined lengths, and the individual glass tubes are
then converted into containers.
❖ In addition to silica, soda ash and limestone, other compounds are added in trace amounts to
achieve certain properties in the glass formed.

❖ For example:
• Alumina (Al2O3) increases the hardness, durability and clarity of the glass.
• Selenium or cobalt oxides improve clarity.
• Lead oxide gives clarity and sparkle (but makes glass soft).
• Boron compounds give low thermal expansion and high resistance to heat shock.
• Arsenic trioxide and sodium sulphate are added to reduce blisters in the glass.

❖ Opacity and different colours are also achieved by the inclusion of compounds.
❖ The different colours convey specific properties. For example:
• Amber glass is widely used to package pharmaceuticals susceptible to degradation
by sunlight.
• Green glass is mostly used for packaging beverages.
• Blue glass makes white products appear whiter.
• Opaque white (opal) conveys prestige to upmarket toiletries and cosmetics.

Additives that are generally

used to achieve different colours
of glass
Glass is not totally inert:

❖ Although glass is fairly inert, it is not totally inert , glass is composed principally of silicon dioxide,
together with various amounts of other oxides, such as sodium, potassium, calcium, magnesium,
aluminium, boron and iron.

❖ The basic structural network of glass is formed by the silicon dioxide tetrahedron. Whilst boric
oxide will enter this structure (and thereby be held more strongly), the other oxides do not enter
the silica tetrahedron and are only loosely bound, and are therefore free to migrate.

❖ Thus some of the glass components can leach out of the glass and into the contents of the
container.
❖ For example, sodium oxide can leach out from the glass surface into water contained within the
container.

❖ The leaching event is an ion-exchange process and involves the exchange of hydrogen ions (from
the water) for the alkali ions (from the glass).

❖ As a result, the pH of the contents is increased.

❖ Another problem occurs when glass is stored at high temperature and high humidity or when
ambient temperature and humidity conditions fluctuate greatly. Salts in the glass migrate from
the body of the glass and accumulate at its surface. This physical change is called blooming.

❖ Such problems are obviously unacceptable.

❖ To reduce leaching, the glass can be soaked in heated water or a dilute acid solution, which
removes most of the surface-leachable salts.

❖ The inner surface of a glass container can also be treated (e.g. with a sulphur compound) to make
it more resistant to water or acidic (but not alkaline) solutions.

❖ In addition to leaching of glass components from the glass into the container contents, glass can
undergo delamination, i.e. dislodging of thin layers of glass called lamellae or flakes from the
inner surface, as a result of dissolution by hydrolysis and leaching of glass components.

❖ The factors which influence delamination include :

• the quality of the glass,
• the nature of the contents,
• the glass manufacturing and
• any sterilization processes.
Pharmaceutical types of glass and containers
❖ Glass containers for pharmaceutical use are produced from either borosilicate (neutral) glass or
soda–lime–silica glass.
❖ The containers are classified in international pharmacopoeias according to their hydrolytic
stability: the inner surface of the container or glass grains are made to contact water and the
release of alkali ions from the glass into the water is measured.

i. Type I glass and containers:

• Type I glass is the highest pharmaceutical grade. It is the most inert glass and shows high
hydrolytic resistance (i.e. low leaching of glass components into water) and high resistance to
thermal shock because of the chemical composition of the glass itself.
• This glass can therefore be used during severe sterilization procedures.
• This glass is also the most expensive to produce.
• Type I glass containers are suitable for most parenteral and nonparenteral products.
ii. Type II glass and containers:
• Type II glass containers are made from soda–lime–silica glass.
• This glass itself has a moderate hydrolytic resistance because of its chemical composition.
However, treatment of the inner surface of the glass container with sulphur dioxide increases the
hydrolytic resistance of the container, as the sulphur dioxide reacts with the oxides found on the
glass surface.
• Type II glass is also referred to as treated soda–lime glass or dealkalized soda–lime glass.
• Type II glass containers are suitable for most acidic and neutral aqueous preparations for
parenteral and nonparenteral uses.

iii. Type III glass and containers:

• Type III glass is soda–lime–silica glass and has moderate hydrolytic resistance.
• Type III glass containers are suitable for nonparenteral preparations.
• Because of the moderate hydrolytic resistance, they are generally not used for aqueous
parenteral products.
PLASTICS:

❖ The versatility of plastics has led to their use in almost all aspects of our lives, and they are used
to package a wide variety of domestic products.
❖ They are widely used as containers (e.g. bottles, trays), closures (e.g. screw tops), cling films,
carrier bags, sacks, overwraps, etc.
❖ Plastics are also widely used to package medicines in a variety of ways, such as:
• bottles for solid and liquid products;
• tubes for creams, ointments and gels;
• pouches to contain individual suppositories;
• blister packs;
• bags to contain intravenous solutions and parenteral nutrition products;
• overwraps;
• bottle closures and closure liners; and
• tamper-evident films over bottle necks and stoppers.
Advantages and limitations of plastics:

• The use of plastics as a pharmaceutical packaging material is growing because of the significant
advantages and consumer preference.
• Plastics are lightweight and shatterproof, and can be clear or opaque (clarity may be desired for
product inspection; opacity may be desired to protect the contained medicine).
• Plastics are easily shaped and sealed, which gives great versatility in the design of the pack, and
allows the inclusion of administration aids, such as a squeezable dropper.
• The many plastic materials, with a range of physical, chemical, optical and performance
properties, enable great versatility.
• However, they are not as chemically inert and impermeable (to environmental gases, such as
oxygen) compared with type I glass.
• Plastics are less resistant to heat and long-term light exposure compared with glass and metal.
• Plastics are also liable to undergo stress cracking, where the presence of solvents, such as
alcohols, acids or oils, causes a plastic pack to become brittle, crack and eventually fail over time.
• Certain components of the plastic packaging material can also leach out of the plastic and into the
contained product.
• At the same time, drug and excipients can adsorb to, or absorb into, the plastic material.
Rubbers and elastomers:

• Rubber has many applications in pharmaceutical packaging, for example, closures for vials and
bottles, and ports on plastic bags used to contain parenteral nutrition products.
• Elastomers are polymers that can be stretched (to more than twice their original length) and
which return to their original length once the force is removed.
• Elastomers may be natural (extracted from rubber trees) or synthetic (derived from
petrochemicals), and common pharmaceutical examples include butyl, chlorobutyl, natural and
silicone elastomers.
• Rubbers are formulations of these elastomers and, in addition to the elastomer polymer, contain
a number of substances (2–10) such as fillers, vulcanizing agents, cure accelerators, activators,
plasticizers, lubricants, antioxidants and pigments.
• To produce rubber formulations, the elastomer and other required materials are placed in a
mixer, which breaks the materials into small fragments and produces a uniform dispersion.
• The latter, a viscous liquid, is placed in a heated mould, where heat and pressure promote
polymer cross-linking and ‘cure’ the formulation, such that a strong, tough and elastic rubber is
produced.
• The rubber is then trimmed and washed to remove residual materials that may have migrated to
the surface during moulding.
• Residual materials may also be extracted from the rubber by different techniques, such as
autoclaving.
• The rubber surface may be treated with chlorine to produce a shiny glaze or coated with
materials, such as silicon oils, to reduce the coefficient of friction.
• Like other polymers, rubbers are not totally inert.
• They are permeable to some extent to gases and moisture; they may also sorb components of the
packaged product, and residues and low molecular weight components may leach from them into
the packaged contents.
• Other properties of rubber include its elasticity, hardness, pressure to puncture, tendency to
fragment, coring and resealability (following puncture with a hypodermic needle used to remove
the contents), break force and vacuum retention.
• For rubber closures in vials/bottles, the rubber should be hard enough to be firm yet allow easy
insertion (and removal) of a needle through a vial closure.
• Appropriate elasticity will allow a good seal between the closure and the container, and permit
resealing on removal of a hypodermic needle.
• The rubber should fragment minimally when pierced by a hypodermic needle.
Metal:

❖ Metal is widely used to package food, beverages, aggressive products, etc.

❖ Aluminium and tinplate (a sheet of steel that is coated with a thin deposit of tin) are the metals
used in the packaging of pharmaceuticals.
❖ They are used in the form of cans (e.g. pressurized metered-dose inhaler (pMDI) containers),
tubes (for creams, ointments, gels), pouches (for powders, granules, liquids, suppositories), blister
packs and closures.
❖ Metal has many advantages as a packaging material:
• It is mechanically strong and can withstand the high internal pressure in pMDI
containers.
• It is shatterproof, lightweight (because it is strong even when thin layers are used),
impermeable to gases and light and malleable.
• It can be tailored in hardness and flexibility with respect to the desired container.
• Both soft and hard forms of aluminium and tinplate are used in pharmaceutical packaging; hard
material is used for its strength and durability in containers such as aerosol cans, whilst soft and
malleable metal is used to produce collapsible tubes and flexible pouches and as the
collar/overcap on parenteral vials with rubber stoppers.
• Malleability allows the metal collar/overcap to be crimped in place and flexible pouches and
metal tubes to be crimped closed.
• The metal's malleability also means that when metal tubes are squeezed to expel the product
(e.g. a cream), the tube does not spring back to its original shape and air is not sucked back into
the container, which could otherwise react with the product or cause it to dry out.
• However, it interacts with the pharmaceutical product.
• To isolate the metal from the product, the metal surface is coated with vinyl-, acrylic- and epoxy-
based resins.
• The outside of the metal container is also coated to enable printing.
Paper:

❖ Paper is one of the oldest pharmaceutical packaging materials.

❖ It has diverse applications, including labels and leaflets, collapsible and rigid cartons, bags and
sacks and sachets.
❖ Unlike the other packaging materials – glass, metal and plastic – paper is not usually used in the
manufacture of the primary pack.
❖ An exception is the sachet, where the paper is separated from the product by a layer of another
material.
❖ Paper is defined as a matted or felted sheet usually composed of natural plant fibre.
❖ When the paper material weighs 250 g/m2 or more, or is 300 μm or more in thickness, it is known
as paperboard.
❖ Softwood from spruce, fir, pine and eucalyptus trees is now the most common source of fibre in
papermaking, although bagasse (from sugar cane), cotton, straw, flax, bamboo, jute, hemp, grass,
esparto, rags and sisal have also been used.
Advantages and disadvantages of paper as a packaging material:

❖ Paper has many advantages as a packaging material, including:

• Its relatively low cost and ready availability.
• Its generally nontoxic origin.
• Its easy recyclability.
• It is readily torn or cut open, an advantage when paper is used in sachets.
• Its ‘deadfold’ (ability to hold a crease) allows the making of cartons and bags as well
as its use for patient information leaflets.
• Its rigidity and strength allow its use in cartons. At the same time, it can act as a slight
cushion to protect the primary pack.
• It is easily printed on and coated.
• The nature and properties of the finished paper can be controlled, such that paper
may be tailor-made for specific applications. (i.e. its opacity and colour can be varied by
the use of additives, and its porosity can be adjusted to allow diffusion of steam for
sterilization while maintaining a barrier to microorganisms.)
❖ Paper does have certain disadvantages, and these result in it not generally being used on its own
in the primary pack.

❖ These disadvantages include:

• The lack of barrier properties against moisture, gases and odours.
• It is moisture sensitive.
• It has no heat- or cold-seal properties and hence cannot be sealed without adhesives or
special coatings.
• It has poor transparency and gloss compared with certain plastic films.

❖ To overcome such disadvantages, paper can be combined with other materials.

❖ For example, paper can be further coated by polymers, or laminated to plastic or to aluminium
foil to improve its barrier properties with regard to gases and moisture, and to create heat-sealing
ability when it is used in the primary pack.
Laminates:

❖ A laminate is made by the bonding together of two or more plies (layers) of different materials,
such as paper, plastic and metal.
❖ The aim is to combine the desirable properties of the different plies into a single packaging
structure.
❖ A minimum amount of material is used, and the laminate is cost-effective.
❖ Laminates are used to produce pharmaceutical packs such as sachets, blister packs, tubes and
pouches. E.g. the structure consisting of paper, metal foil and polythene plies, used for sachet
packaging.
❖ The paper provides strength, printability and the ability to easily tear the package, the foil
provides an excellent barrier to light, moisture and gases and the polythene provides heat
sealability.
Packaging and regulatory bodies:

❖ Like the drug substance and drug product, the pharmaceutical packaging is subject to regulation
and approval by government agencies, such as the US Food and Drug Administration, the
European Medicines Agency and the UK’s Medicines and Healthcare products Regulatory Agency.
❖ The packaging is considered part of the product, and manufacturers must submit large amounts
of data to show that the packaging is safe, is effective and performs as claimed.
❖ The regulatory bodies produce guidance documents to assist manufacturers, such as on labelling,
patient information leaflets, closures and the testing of containers.
❖ The United States Pharmacopeia includes requirements for containers, and many of the drug
product monographs include the requirements for packaging, such as ‘preserve in single-dose
containers, preferably in Type I glass, protected from light’.
❖ Labelling and patient information leaflets are part of the pack and are also subject to regulation.
Designing packaging for safe medicine use:

❖ A quarter of medication errors – which are common and cause significant morbidity, mortality
and cost – have been attributed to medicines which have similar names (similar looking and
similar sounding names) or similar packaging.
❖ For example, at least 15 children died following vaccination against measles in northern Syria in
2014, when atracurium was mistakenly used instead of sterile water.
❖ Both vials had a similar appearance, and the atracurium vials had been incorrectly added to
vaccination packs.
❖ While different medicines can have similar packaging, the same medicine can have a wide range
of outer packaging, due to the existence of multiple manufacturers and distributors of generic
products.
❖ Attempts by pharmacy departments to buy the cheapest medicines can result in the pharmacy
department having stock from multiple suppliers for the same medication, which can lead to
errors in recognizing and using the medication.
❖ Clearer packaging has to be ‘designed in’ to both primary and secondary packs to prevent such
errors.
❖ Actions that would result in clearer and safer packaging, such as global standardization of the
packaging, have been recommended by a number of researchers and institutions.
❖ Other examples of good practice include:
• choosing medicine names that are least likely to be confused with the names of existing
medicines;
• designing packaging that is easy to read (e.g. use of nonreflective foil on blister packs,
large and clear fonts with a good contrast to the background);
• appropriately aligning text for easy reading;
• emphasizing the difference between look-alike or sound-alike (LASA) medicine names,
with use of colour, font size or tall man lettering (e.g. chlorproPAMIDE and chlorproMAZINE),
and between strengths of the same medicine;
• ensuring that company logos and images do not break the text;
 • allocating space on packs for the dispensing label;
• matching the styles of primary and secondary packaging;
• using dispensing labels of sufficient size and attaching these to the medicine packs
appropriately; and
• using dispensing bags to reinforce key safety messages.

Clearly pharmacists and pharmaceutical scientists can make a significant contribution to reducing
packaging-related medication errors, given their roles in dispensing and labelling medicines, as well
as in the pharmaceutical industry, including in packaging and marketing products.
KEY POINTS:

❖ The pharmaceutical pack is as important as the medicine it contains. The pack provides
containment, protection, presentation, identification, information and convenience and aids with
patient adherence. In some cases, the pack is essential for the medicine's administration.

❖ The closure, such as a stopper, lid, top or cap, is an integral part of the pack.

❖ The primary pack (also called the container-closure system) is in direct contact with the medicine.
It must be compatible with the medicine, and must not change it in any way.

❖ A pack can be a single-unit pack (e.g. a sachet) or a multiple-unit pack (e.g. a bottle containing
many tablets).
❖ Glass, plastics and metal are the most commonly used primary packaging materials. Paper is used
mainly in the secondary packaging. The latter holds/covers the primary pack.

❖ Laminates – consisting of plies (layers) of different materials such as paper, plastic and metal –
combine the advantages of the different materials, and are used, for example, in sachets.

❖ Packaging must be designed for the safe use of medicines.

Brainstorm innovative packaging ideas
Here are some innovative packaging ideas that could enhance sustainability, functionality, and
consumer experience:

Edible Packaging: Create packaging made from edible materials that can be consumed along with the
product, reducing waste and providing a unique experience.

Biodegradable Materials: Use materials derived from natural sources, such as corn-starch or
mushroom mycelium, that break down easily in the environment.

Smart Packaging: Incorporate QR codes, NFC tags, or AR technology that customers can scan for
more information about the product, including sourcing, sustainability practices, and usage tips.

Reusable Containers: Design packaging that can be repurposed after use, such as jars or boxes that
can function as storage solutions.
Modular Packaging: Create packaging that can be reshaped or reconfigured, allowing consumers to
adjust the size based on their needs or taste.

Plantable Packaging: Use seed-infused paper or containers that can be planted after use, allowing
consumers to grow flowers, herbs, or vegetables.

Zero-Waste Packaging: Develop a system where customers return used packaging for refills,
promoting sustainability and reducing single-use plastic.

Interactive Packaging: Design packages with games or activities that engage consumers, making the
unboxing experience more enjoyable.

Climate-Sensitive Materials: Utilize materials that change colour or texture based on temperature,
indicating freshness or spoilage.
Multi-Functionality: Create packaging that serves a dual purpose, such as a box that can be
transformed into a display stand or a container that doubles as a tool or utensil.

Customized Packaging: Use on-demand printing technology to create personalized packaging for
each customer, enhancing their connection to the product.

Transparent Packaging: Use materials that allow consumers to see the product inside, enhancing
trust and desirability.
Discuss challenges in pharmaceutical packaging
Pharmaceutical packaging faces several challenges that can impact safety, compliance, and consumer
trust. Here are some key challenges:

Regulatory Compliance: Pharmaceutical packaging must adhere to stringent regulations set by

health authorities (e.g., FDA, EMA). Ensuring compliance with labelling, child-resistance, and quality
standards can be complex and time-consuming.

Counterfeit Prevention: The rise of counterfeit drugs poses a significant risk. Packaging must
incorporate anti-counterfeiting measures, such as holograms, tamper-evident seals, and unique
serialization, to ensure authenticity.

Stability and Shelf Life: Packaging must protect against environmental factors such as moisture, light,
and temperature fluctuations that could degrade the medication’s efficacy. Selecting appropriate
materials and designs is crucial for maintaining stability.
Patient Safety: Ensuring that packaging is easy to open yet secure is a delicate balance. Child-
resistant packaging is vital, but it should also be accessible for elderly or disabled patients.

Sustainability: The pressure to adopt eco-friendly packaging solutions while still meeting
performance and safety standards is growing. Finding sustainable materials that do not compromise
product integrity can be challenging.

Supply Chain Disruptions: Global supply chains have been affected by factors like pandemics and
geopolitical issues, impacting the availability of packaging materials and affecting overall production
timelines.

Technological Integration: Incorporating innovative technologies (e.g., RFID, IoT) for tracking and
monitoring can enhance safety and supply chain management but may require significant investment
and expertise.
Cost Management: Developing high-quality, compliant packaging can be costly. Pharmaceutical
companies must balance cost efficiency with the need for advanced features and safety measures.

User Education and Labelling: Clear communication on packaging is essential for patient
understanding. Complex dosing instructions or warnings must be conveyed effectively to prevent
misuse and ensure adherence.

Market Variability: Different markets may have varying regulatory requirements or cultural
considerations that need to be addressed in packaging design and functionality.

By addressing these challenges, pharmaceutical companies can enhance the overall effectiveness of
their packaging, ensuring safety, compliance, and consumer trust while contributing to better health
outcomes.
The use of colour in pharmaceutical packaging plays a significant role in drug expectancy, influencing
both consumer perception and behaviour.

Here are some key aspects to consider:

Psychological Impact of Colour:

Colours can evoke emotional responses and perceptions. E.g.
• Blue may convey trust and reliability, often chosen for brands focused on health and safety.
• Red can signify energy or urgency, but may also evoke caution, making it suitable for products
needing attention.
• Green is often associated with healing and nature, appealing to consumers seeking natural or
organic solutions.
• Yellow can represent optimism but may reduce perceptions of medication efficacy if
overused.
Association with Drug Efficacy:
Colour can impact expectations regarding a drug's effectiveness. For instance, consumers may
perceive brightly coloured pills (e.g., orange or blue) as more potent than dull-coloured ones like
beige or grey. Research suggests that vibrant colours can enhance perceived efficacy.

Brand Differentiation:
Colour helps differentiate products in a crowded market, making them easily identifiable. Consistent
use of colour in branding reinforces brand recognition, aiding consumers in quickly locating familiar
medications.

Consumer Behaviour and Preference:

Certain demographics may show preferences for specific colours, impacting purchasing behaviour.
Understanding target consumer groups can help tailor packaging to enhance appeal.
Regulatory Considerations:
Pharmaceutical companies must consider that colour choice may be influenced by regulations that
dictate how drugs are presented, particularly to avoid confusion with other products.

Cultural Significance:
Colour meanings vary across cultures. For example, white is typically associated with purity in
Western cultures, while in some Eastern cultures, it may symbolize mourning. Understanding cultural
nuances is crucial for global marketing strategies.

Colour and Patient Compliance:

Attractive and engaging packaging colours can enhance user experience and promote adherence.
Aesthetic packaging may motivate patients to take medications regularly.
Visual Clarity:
Beyond colour, the contrast between text and background can affect readability. In pharmaceutical
packaging, readability is critical to ensure users can understand dosage instructions and safety
warnings.

In summary, the choice of colour in pharmaceutical packaging is a vital consideration that can
influence consumer expectations, perceived efficacy, brand loyalty, and overall patient compliance.
Pharmaceutical companies should strategically select colours that align with their brand identity,
enhance user experience, and comply with regulatory standards.