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Packaging CHAPTER 27
Containers for parenteral products
Small-volume parenteral products, such as subcutaneous injections, are typically packaged in various containers made of Type I glass. Glass ampoules
(Fig. 27.3) are used to package parenteral solutions
intended for single use.
Multiple-dose vials (Fig. 27.4) are used to package parenteral formulations that will be used on
more than one o ccasion. Large-volume parenteral
fluids have been packaged in 500 mL glass containers but these have been largely superseded by
plastic b ags.
Figure 27.3*Glass ampoule.
Plastics
Plastics have been widely used for several years as
containers for the product and as secondary packaging
in the form of a carton. In more recent times, plastic
has been developed for the packaging of parenteral
products including infusion fluids and small-volume
injections.
Two classes of plastics are used in the packaging of
pharmaceutical products. These are known as thermosets and thermoplastics. The thermosets are used
for making screw caps for glass and metal containers.
Thermoplastic polymers are used in the manufacture
of a wide variety of pharmaceutical packages as
detailed in Table 27.2.
The advantages of plastics for packaging are that
they:
*
Release few particles into the product
*
Are flexible and not easily broken
*
Are of low density and thus light in weight
*
Can be heat sealed
*
Figure 27.4*Glass vial.
Table 27.2 The application of thermoplastic polymers for the packaging of pharmaceutical products
Are easily moulded into various shapes
Polymer Examples of application
High-density polyethylene Solid dosage form containers
Low-density polyethylene Flexible eye drop bottles
Linear low-density polyethylene Heat-sealable containers
Polypropylene Container closures, intravenous solution bottles
Polyvinyl chloride Laminate for blister packs, intravenous bags
Polystyrene Containers for oils and creams and solid dosage forms
309
SECTION FOUR Dispensing and related pharmaceutical practice activities
*
Are suitable for use as container, closure and as
secondary packaging
*
Are cheap.
The disadvantages of plastics are that:
*
They are not as chemically inert as Type I glass
*
Some plastics undergo stress cracking and
distortion from contact with some chemicals
*
Some plastics are very heat sensitive
*
They are not as impermeable to gas and vapour as
glass
*
They may possess an electrostatic charge which
will attract particles
*
Additives in the plastic are easily leached into the
product
*
Substances such as the active drug and
preservatives may be taken up from the product.
Plastic pharmaceutical containers are made of at least
one polymer together with additives. The additives
used will depend on the composition of the polymer
and the production methods used.
Additives used in plastic containers include:
*
Plasticizers
*
Resins
*
Stabilizers
*
Lubricants
*
Antistatic agents
*
Mould-release agents.
chemicals and solvents. It is commonly pigmented
or printed white to block light transmission and
improve label clarity. HDPE is widely used in bottles
for solid dosage forms.
Disadvantages of LDPE and HDPE for packaging
are that they:
*
Are softened by flavouring and aromatic oils
*
Are unsuitable for packing oxygen-sensitive
products owing to high gas permeability
*
Adsorb antimicrobial preservative agents
*
Crack on contact with organic solvents.
Polyvinyl chloride (PVC)
This is extensively used as rigid packaging material
and as the main component of intravenous bags.
Polypro py len e
This is a strong, stiff plastic polymer with good resistance to cracking when flexed. As a result it is particularly suitable for use in closures with hinges which
must resist repeated flexing. In addition, polypropylene has been used as tablet containers and intravenous
bottles.
Polystyren e
This is a clear, hard, brittle material with low impact
resistance. Its use in drug packaging is limited due to
its high permeability to water vapour. However, it has
been used for tubes and amber-tinted bottles where
Plastic containers
These are used for many types of pack including rigid
bottles for tablets and capsules, squeezable bottles for
clarity and stiffness are important and high gas permeability is not a drawback. It is also used for jars for
ointments and creams with low water content.
eye drops andnasal sprays, jars,flexibletubes, strip and
blister packs. The composition and the physical shape
Closures
of the containers vary widely to suit the application.
Any closure system should provide an effective seal to
The principal plastic materials used in
pharmaceutical packaging
retain the container contents and exclude external
contaminants. Child-resistant containers (CRCs)
commonly consist of a glass or plastic vial or bottle
Polyethylene
This is used as high- and low-density polyethylene,
both of which are compatible with a wide range of
drugs and are extensively used for the packaging
of various pharmacy products. Of these two forms
of polyethylene, low-density polyethylene (LDPE)
is softer, more flexible and more easily stretched than
high-density polyethylene (HDPE). Consequently,
LDPE is usually the preferred plastic for squeeze bottles. By contrast, HDPE is stronger, stiffer, less clear,
less permeable to gases and more resistant to oils,
with a specially designed closure. These CRCs are a
professional requirement for dispensing of solid and
liquid dosage forms in the UK and are ultimately a
compromise between child resistance and ease of
opening. They are not an absolute barrier to children
accessing medicine containers, therefore the containers should be stored in a safe place. Several designs of
child-resistant closures are currently used for pharmaceutical packaging, including cap–bottle alignment
systems, push down and turn caps and, less commonly, squeeze and turn caps.
310
Packaging CHAPTER 27
Figure 27.5*Snap-safeÒ closure.
The closures in common use with dispensed medicines are the Snap-safeÒ alignment closure (Fig. 27.5)
and the push down and turn Clic-locÒ closure (Fig.
27.6). The Clic-locÒ child-resistant closures are based
on the assumption that young children are unable to
coordinate two separate and dissimilar actions; that is,
applying pressure and rotating the closure top. The
Clic-locÒ closure has a two-piece mechanism with
springs between the inner and the outer parts. As a
result of this design, the closure produces an audible
clicking noise when the cap is turned without first
being depressed. The inner cap is composed of polypropylene while the outer overcap is made of HDPE.
Contamination of the screw thread with crystallized sugar arising from syrups can increase the torque
necessary to open these Clic-locÒ closures. This type
of problem can restrict their suitability for use. Owing
to opening difficulties experienced by some adults,
Figure 27.7*Tamper-evident closure.
these closures should not be used on containers supplied to elderly or handicapped patients with poor
manual dexterity. They should not be used when a
request is made that the product is not dispensed with
a child-resistant closure fitted. A Clic-locÒ closure
must only be dispensed on one occasion as continued
use increases the penetration of moisture vapour into
the container and decreases the child-resistant properties of the closure.
In recent years greater awareness of the vulnerability of products has led to the development of
tamper-evident closures. The closures indicate if
unlawful access to the container contents has occurred
and are currently available in various designs suitable
for differentcontainers and closures. Dispensary stock
containers are frequentlyfitted with a JaycapÒ type of
tamper-evident closure. These closures are made of
either white polypropylene or LDPE. With this closure design the tamper-evident closures snap over a
security bead on the neck of the container. The closures cannot be opened until the tamper-evident band
connecting the cap to the skirt is torn away (Fig. 27.7).
Clic-locÒ closures are available with this design
whereby an external tamper-evident coloured band
must be removed before the closure can be turned.
Tamper-evident inner seals are positioned within the
closure and are attached to the rim of the opening to
the container isolating its contents. The seal must be
torn or removed from the container to gain access to
the packaged product. These seals are commonly
made of a combination of paper, plastic and foil.
Figure 27.6*Clic-locÒ closure.
Collapsible tubes
These are flexible containers for the storage and
dispensing of creams and ointments. Tubes made of
tin are used to package certain sterile formulations.
311
SECTION FOUR Dispensing and related pharmaceutical practice activities
Typically the formulation is aseptically filled into the
pre-sterilized tubes. However, the most common
metal tubes in current use are made of aluminium
with an internal lacquered surface. With this package
the tube remains collapsed as the product is removed.
These tubes are frequently sealed at both ends and the
nozzle must be punctured to access the product. An
alternative seal that can be used with these packages
is a heat seal band between the closure and the container. This band must be torn to gain access to the
container contents.
Plastic tubes made from a variety of materials
are superseding metal tubes. For example, the tube
sleeve may be made of LDPE with either a LDPE
or HDPE head or the entire tube may be made of
polypropylene.
Unit-dose packaging
This term usually means that a single item such as a
tablet or capsule or a specific dose is enclosed within
its own disposable packaging. The most commonly
used methods for unit-dose packaging are blister
packs and strip packs.
Blister packs
These are used for packaging unit doses of tablets and
capsules and can act as an aid for patient compliance.
The medication is placed in a compartment in a base
material made of paper, board, plastic or metal foil or
a combination of these. The blister is generally composed of a thermoformed plastic sheet such as PVC.
The protection given by the plastic blister depends on
its composition, design and the method used to form
it. Perforations in the base material allow individual
sections of the package to be broken off. Blister
packages are rigid, unlike strip packs that are flexible.
Strip packaging
With strip packaging, two webs of material sandwich
various types of medicine such as tablets, capsules,
suppositories or pessaries. Each of these dosage forms
is contained within its own compartment. The composition of the two webs can be selected to meet
the necessary protective requirements for the medicine. Aluminium foil is commonly used to manufacture strip packs and provides a good barrier against
moisture penetration. The foil is used as a laminate in
which the other components add strength to the frag-
ile aluminium foil. They also block small holes which
can occur in the thinner foil layer.
Paper
Paper is used more than any other material in packaging. Although it has an insignificant role in primary
packaging it remains the predominant secondary and
tertiary packaging material. In this role it is used as the
carton which contains the primary package and, in the
form of board, is the corrugated shipping container
which contains both.
Patient pack dispensing
A patient pack consists of a course of medication
together with a patient information leaflet in a ready
to dispense pack. Liquid formulations are supplied in
a standard pack. Solid dose forms are supplied as a
strip or blister pack. The size of the sealed patient
pack is based on a 28, 30 or 56 dose unit appropriate
to the medicine. It is supplied in this amount unless a
doctor prescribes that a different quantity of medicine is to be dispensed. The patient pack contains an
information leaflet as an aid to improving patient compliance and to supply information to patients about
their medication. Pharmacists should be prepared to
respond to enquiries after the patient has read the
leaflet. The patient pack is designed as a balance between the need for child resistance and the need for
ease of opening by the elderly. If requested by the
patient, the pack contents can be repackaged in a
more suitable container.
Advantages of patient packs
*
They contain product information such as product
and manufacturer identification and the batch
number
*
More efficient dispensing results in greater
opportunity for patient counselling
*
More information is supplied to the patient about
the product.
Disadvantages of patient packs
*
Increased storage space is required
*
Elderly and debilitated patients may experience
difficulty in opening the pack.
312
KEY POINTS
*
Containers should preserve the quality of a
medicine for its stated shelf life
*
Glass has both advantages and disadvantages in
use, but remains the preferred material in many
situations
*
The types of glass have different uses:
Type I for ampoules and vials
T
Type II for eye preparations and dropper
T
bottles
Type III for metric medical bottles
T
*
Fluted bottles are used for preparations not
intended to be swallowed
*
Plastics may be thermosets or thermoplastics
Packaging CHAPTER 27
*
A variety of additives to plastics may enter
medicines with which they are in contact
*
Child-resistant containers (CRCs) may have
alignment closures (Snap-safeÒ) or push and turn
(Clic-locÒ)
*
Use of CRCs is a professional requirement for
dispensed medicines unless requested otherwise
*
Tamper-evident closures indicate that there has
been no unlawful access to the medicine
*
Aluminium is being replaced by plastics for
collapsible tubes
*
Unit dosage packaging may be either blister or strip
packaging
*
The main use for paper is for cartons and boxes
*
A patient pack consists of the medicine and patient
information leaflet in a ready to dispense outer pack
313
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Chapter Twenty-Eight
Labelling of dispensed medicines
Judith A. Rees
28
STUDY POINTS
*
The reasons for having labels on dispensed
products
*
Requirements for labels
*
Standard details required on labels
*
Additional labels
*
Specific UK legal requirements
*
Patient-specific labels
Introduction
All dispensed medicines should be individually
labelled by the dispenser. The label on a dispensed
medicine has several main functions:
*
To uniquely identify the contents of the container
*
To ensure that patients have clear and concise
information which will enable them to take or use
their medicine in the most effective and
appropriate way
*
To clearly identify the patient for whom the
medicine is dispensed
*
To satisfy legal requirements.
In the UK there are both legal (UK and EU) and
professional requirements which must be complied
with when labelling a dispensed medicine. It is the
pharmacist’s responsibility to ensure that these
requirements are satisfied and that all labelling is accurate and comprehensible. The regulations indicate
standard details which must appear on every label. In
certain circumstances additional details are also required. Useful sources of information are Medicines,
Ethics and Practice and the British National Formulary (BNF). In this chapter only the requirements for
the labelling of dispensed medicines in the UK are
dealt with. However, similar requirements will be in
place in other countries. It should also be noted that
provision of an adequate label does not remove the
need to give advice and counselling to the patient (see
Ch. 44).
Standard requirements for labelling dispensed medicines
All labels must be in printed form, either typewritten
or computer generated. This should mean that the information on the label is legible; however, there have
been reports of labels which were unreadable because
the printer was not working properly or the ink or
toner cartridges were low or empty. Hence there is
a need for pharmacists or dispensers to check each
label for legibility before handing the item to the
patient. It is also important that the font size of the
print is suitable for the patient (see later).
In summary, the details which must appear on the
label of a dispensed medicine are:
*
The name of the preparation, strength and form
(if more than one available)
*
The quantity
*
Instructions for use
*
Precautions relating to the use of the product
*
The patient’s name
*
The date of dispensing
*
The name and address of the pharmacy
*
‘Keep out of the reach and sight of children’
*
The phrase ‘For external use’ for certain
formulations.
SECTION FOUR Dispensing and related pharmaceutical practice activities
Additional labelling requirements
*
Warning or advisory labels should be attached to
the container, where appropriate
*
A batch number should be indicated if the
preparation has been prepared extemporaneously
*
An expiry date should be indicated if the
preparation has been prepared extemporaneously
or the shelf life has been shortened, e.g. a diluted
preparation
*
Additional legal requirements, e.g. ‘For animal
treatment only’ on veterinary prescriptions
*
Storage conditions.
The name of the preparation,
strength and form
The name which appears on the label must be the
same as the one which appears on the prescription.
The preparation may be prescribed generically but
only be available as a proprietary or branded product;
however, the prescribed name must be used. The
reason for this is to avoid the patient becoming confused with a variety of names.
The letters NP on a prescription stand for ‘nomen
proprium’ – the proper name of the medicine. Occa-
sionally a prescriber may not wish the name of the
preparation to appear on the container. To indicate this
they will delete the NP instruction on the prescription.
In these cases the type of medicine (e.g. ‘the tablets’,
‘the mixture’) shouldreplace the name of the product.
Another occasion when the name may be omitted
is when the product contains several active ingredients and has no official or proprietary name and it
would be extremely difficult to list all the ingredients
on the label. In these instances the pharmaceutical
form is used, e.g. ‘the ointment’, ‘the mixture’.
If the preparation is available in more than one
strength, the strength must be included on the label,
for example, amoxicillin 250 mg capsules and amoxicillin 500 mg capsules. Such information clearly
identifies the medicine.
Similarly, the form of the medicines should be included on the label. This is especially important if the
product is available in more than one form (e.g. amoxicillin capsules, syrup, suspension, sachets, injection).
The inclusion of the form identifies the medicine and
may give an indication of how it is to be used/taken
(e.g. forms such as suppositories, inhalations, enemas).
Quantity and multiple packs
Normally the quantity which appears on the label will
be the quantity which has been prescribed. Nowadays,
many medicines are supplied in the manufacturer’s
patient packs, which will be labelled according to
the legal requirements. If the quantity on the prescription requires more than one of these patient packs to
be dispensed, for example two patient packs each
containing 28 tablets of the same medicinal product
(a total of 56 tablets), then the quantity on the label
should be the amount in each container. In other
words each container should be labelled.
Where several containers (manufacturer’s patient
packs) of the same medicinal product are required to
supply the quantity stated on the prescription (multiple packs), then the name of the product, directions
for use and precautions relating to the use of the
product need only appear on the package containing
the individual packs or on one of the individual packs.
All the individual packs must be labelled with the
name of the patient, the name and address of the
pharmacy, the date of dispensing and the words ‘keep
out of the reach of children’.
Instructions for use
No patient should leave a pharmacy without knowing
how much, how often and how to use/take his or her
medication. Although the label should be seen as a
back-up to the verbal counselling and advice given by
the pharmacist, it is still essential to ensure that the
wording on the label is clear, concise and comprehensible to the patient. The prescriber’s instructions
should therefore be translated into an appropriate
form. If instructions are missing or incomplete it
is the pharmacist’s professional duty to obtain
instructions from the prescriber or use professional
discretion to interpret BNF statements.
The way in which instructions are worded is very
important and will greatly influence how easily a patient understands the message. Pharmacists should
therefore give serious consideration to the wording
on medicine labels.
The Royal PharmaceuticalSociety working party report(1990)on ‘The Labellingof DispensedMedicines’
made several recommendations. The use of active
verbs is preferred, e.g. ‘take’ instead of ‘to be taken’,
‘apply’ instead of ‘to be applied’. The reason is that
research has shown that active verbs are more easily
understood and remembered than passive verbs. It is
316
Labelling of dispensed medicines CHAPTER 28
Table 28.1 Recommended wording for directions
Recommended wording Wording to be replaced
Do not swallow Not to be taken
Take ‘x’ times a day, spaced evenly through the day
(This wording was considered preferable for antibiotics)
Put two drops in the affected eye Instil two drops in the affected eye
For creams or ointments:
Spread thinly Use sparingly
For pessaries or suppositories:
Gently put one into the vagina/rectum Insert one into the vagina/rectum
bad practice to havetwonumbersappearingtogetherin
instructions,e.g. ‘take two three times daily’.Itiseasy
for a patient to mentally transpose the position of the
numbers so that the previous instruction becomes
‘three twice daily’ in the patient’s mind. To avoid this,
the numbers should always be separated by using the
formulation name, e.g. ‘take two tablets’, ‘two capsules’, ‘two powders three times daily’. Other recommendations in the report can be seen in Tab l e 2 8 . 1 .
Numbers which are part of an instruction must
always be written as words except in the case of 5 mL,
whenreferringto a 5 mL spoonful, or oralsyringequantities,e.g.a 2.5 mL dose using the oralsyringeprovided.
Many manufacturers’ packs of medicines contain a
patient information leaflet. These normally give detailed instructions (with illustrations) of how to use a
medicine, along with other details about the medicine. Patients should be told to read the patient information leaflet before using the medicine. This is a
back-up to the labelling.
medicines. If possible, the status of the patient,
i.e.Mr,Mrs,Miss,Master,ChildorBaby,should
be included in order to clearly differentiate from
other members of a household, where there may be
other persons with the same name. For the same
reason a full first name should also be included
if possible, rather than an initial, e.g. Mr James
Burnett instead of J. Burnett.
The date and name and
address of the pharmacy
The majority of pharmacies use computer systems for
prescription labelling and this information will normally appear automatically, with the date being reset daily. This information is a legal requirement, but
enables the source of the medicine to be traced and
date of dispensing, if necessary. For example, in the
case of possible overdose or poisoning, the label would
assist any investigation.
Take every ‘y’ hours
(For analgesics this remains the desirable wording)
Precautions relating to use of
the product
Labelling the product with precautions relating to use
is for safety reasons. Such labelling will be specific to
the product and includes ‘Caution flammable: keep
away from fire or flames’ and ‘Not to be consumed by
mouth’.
The patient’s name
It is a legal requirement that the name of the
patient for whom the medication has been prescribed must appear on the label of all dispensed
‘Keep out of the reach of
children’
In order to prevent accidental ingestion of medicines by children, all dispensed medicines are required to carry the label ‘ Keep out of the reach of
children’. Any pharmacist in the UK who issues a
dispensed medicine without this warning on the
label is guilty of contravening the Medicines Act.
Nowadays it is recommended that the wording ‘Keep out of the reach and sight of children’
is used for consistency because this wording is
used on all labels of manufactured patient packs
of medicines.
317
SECTION FOUR Dispensing and related pharmaceutical practice activities
Additional labelling
requirements
In addition to the standard details required on all
dispensed medicines there are several extra details
which are required in certain circumstances. Some
information may be specific to a particular type of
formulation.
Storage
General information for different types of preparation can be found in the relevant chapters in this
book. Some formulations require special storage
and this information should be attached to the label,
e.g. transdermal patches should be stored in a cool
place. Other labels relating to storage include ‘protect from light’ and ‘store in a fridge’. Any specific
pharmaceutical precautions relating to storage
should always be indicated, for example glyceryl
trinitrate tablets should be labelled ‘discard after
8 weeks of use’.
The British Pharmacopoeia (and other pharmacopoeias) use the terms ‘freshly prepared’ and ‘recently prepared’ for extemporaneously prepared
products with a s hort keeping time. ‘ Freshly prepared’ is defined as having been made no more than
24 hours before issue for use, but there is no indication of when it should be discarded. In this case, it
is usual to give a 1 week discard date. The term
‘recently prepared’ is used for products which
should be discarded 4 weeks after issue when stored
at 15–25
accessed in the Association of British Pharmaceutical
Industries (ABPI) Medicines Compendium.
Warnings for patients
Ideally, any liquid preparation should state ‘Shake the
bottle’, and ‘For external use only’ is a legal requirement on external liquid and gel preparations.
patient should be informed. Information on these
can be found in Appendix 9 of the BNF (BNF no.
56, September 2008; note that the appendix number may be different in later editions). It is a professional requirement, subject to the pharmacist’s
discretion, that if indicated, these special warn ings
C.
Information on proprietary medicines can be
Many drugs cause side-effects about which the
should be affixed to the container. Nowadays most
computer systems will automatically print these
warnings when a label for a particular drug is being
produced. However, there are instances when use of
this information is inappropriate and professional
discretion should be used. For example, the antihistamine chlorphenamine requires the warning:
‘Warning. May cause drowsiness. If affected do
not drive or operate machinery. Avoid alcoholic
drink’. Young children may be prescribed a drug
such as this but this warning would be inappropriate.
Obviously it is important to draw attention to the
problem of sedation and in this case the more suitable warning ‘Warning. May cause drowsiness’ could
be used. If a doctor does not wish the warning labels
to appear, the prescription should be endorsed
‘NCL’ (no cautionary labels).
Some of the BNF warning labels have been known
to cause confusion, such as numbers 5, 6, 7, 11 and 14.
All of these may require additional explanation to be
given to the patient.
*
Label number 5: ‘Do not take indigestion remedies
at the same time of day as this medicine’.
*
Label number 6: ‘Do not take indigestion remedies
or medicines containing iron or zinc at the same
time of day as this medicine’.
*
Label number 7: ‘Do not take milk, indigestion
remedies or medicines containing iron or zinc at the
same time of day as this medicine’.
Some patients misunderstand the information on
these three labels and think that milk, iron preparations and indigestion remedies must not be taken at
all. It should be explained to the patient that as long as
there is an interval of approximately 2 hours between
taking the medicine and any of the remedies, there is
not a problem.
*
Label number 11: ‘Avoid exposure of skin to direct
sunlight or sun lamps’.
There h ave been reports of patients who were
frightened to venture outside when taking medication which carried this warning. Again an explanation that as long as exposed area s of skin are
adequately covered, e.g. a long-sleeved shirt or a
sunhat to shade the face, the patient should not
suffer any ill effects.
*
Label number 14: ‘This medicine may colour the
urine’.
It is useful to give the patient an indication of the
colour, e.g. phenolphthalein (pink), levodopa (dark
reddish) or rifampicin (red).
318