Packaging, storage and labeling

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Packaging, storage and labeling

Learning Objectives
At the end of this topic students will be able to:
 Discuss the different types of containers available for
pharmaceutical packaging
 Describe the labeling requirements for different pharmaceutical
product
 Discuss the need for different storage conditions for different
pharmaceuticals

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 Introduction to packaging…
 Is the process by which the pharmaceuticals are suitably
packed so that they will retain their therapeutic effectiveness
from the time of their packaging till their consume

 Pharmaceutical formulations must be suitably contained ,

protected and labeled from the time of manufacture until the
patient uses them

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 Introduction to packaging…

 Throughout this period the container must maintain the quality,

safety and stability of the medicine and protect the product
against physical, climatic, chemical and biological hazards
 To promote good patient compliance the container must be user
friendly.
 Factors also be considered in the selection of the container used
to package a pharmaceuticals, including the cost and the need
for both child-resistant closures and tamper-evident seals.

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Introduction to packaging…
 Bulk medicines are repackaged into smaller quantities in
dispensing containers for distribution to hospital wards, clinics
and general practitioners for direct supply to patients.

 The composition of containers and closures used for the

repackaging of bulk medicines must be carefully selected

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 Introduction to packaging…

 The label on dispensed medicines has two main functions:

 To uniquely identify the contents of the container.

 To ensure that patients have clear and concise information to

use their medicine in the most effective and appropriate way.
 The pharmacist should comply with different legal and
professional requirements while labeling a dispensed medicine.

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 Introduction to packaging…
 It should also be noted that provision of an adequate label does
not remove the need to counsel the patient.

 There is a need to specify storage conditions and a shelf life,

 To ensure effective stock control and pay attention to the

packaging used in dispensing.

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Packaging for Pharmaceuticals
 According to the USP, container is the device that holds a drug
and is, or may be, in direct contact with the drug.
 the device which is in direct contact with the drug at all times
is termed as
– the immediate container-USP
– primary packaging-BP

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 Characteristic of packaging

 Protect from environmental conditions

 Should be inert/ not reactive with product

 Must not impart the test or odor to the product
 Non toxic

 FDA proved
 Must meet temper resistant requirement

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 Definition of terms with regards to
pharmaceutical containers:

 Single-dose containers: these are containers which hold the medicine

that is intended for single use.
– E.g. glass ampoule.
 Multidose containers: these hold a quantity of the material that will
be used as two or more doses.
– E.g. multiple dose vial or the plastic tablet bottle.

 Unit of Use Packaging: this is packaging in which an amount of drug

product to be used during the usual course of a patient’s treatment, or
an otherwise commonly prescribed amount of that drug.
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 Definition, cont’d

 Well-closed containers: this is the minimally acceptable container

in the USP, and protects the product contamination with
unwanted foreign materials and form loss of contents during
handling, shipment, storage, distribution and use.

 Airtight containers (tight containers-USP): are impermeable to

solids, liquids and gases during normal storage and use. A tight
container is capable of re-closure to its original capability after
being opened.
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 Definition, cont’d

• Sealed Containers (Hermetic Container-USP): such as glass

ampoules are closed by fusion of the container material.
 It is impervious to air or any other gas under the ordinary or
customary conditions of handling, shipment, storage and
distribution.
 Hermetic containers which are sterile are generally used to
hold pharmaceutical preparations intended for injection or
parenteral administration.

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 Definition, cont’d
• These containers may be:
 single dose (e.g. fusion sealed ampules, prefilled syringe

 multiple dose containers (these containers are commonly

referred to as vials.
• Tamper evident containers: closed containers fitted with a device
that irreversibly indicates if the container has been opened.
• Light resistant containers: protect the contents from the effect of
radiation at a wavelength between 290 nm and 450 nm

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 Definition, cont’d
 Child resistant containers: commonly referred to as CRCs are
designed to prevent children accessing the potentially
hazardous product.
 Strip packs: have at least one sealed pocket of material

with each pocket containing a single dose of the pt.

 The pack is made of two layers of film or laminate
material.

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 Definition, cont’d

 Blister Packs: are composed of a base layer, with cavities that

contain the pharmaceutical product, and a lid.
 This lid is sealed to the base layer by heat, pressure or both.
 They are more rigid than strip packs and are not used for
powders or semi-solids.
 Blister packs can be printed with day and week identifiers to
produce calendar packs, these identifiers will support patient
compliance.

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 Definition, cont’d

 Tropicalized packs: are blister packs with an additional

aluminum membrane to provide greater protection against high
humidity.
 Pressurized packs: are those with expel the product through a
valve.
 The pressure for the expulsion of the product is provided by
the positive pressure of the propellant that is often a
compressed or liquefied gas

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 Definition, cont’d

 Original packs: are pharmaceutical packs that are

commercially produced and intended for finite treatment
periods.
 These packs are dispensed directly to the patient in their
original form.
 Manufacturer’s information is contained on the pack but
the pharmacist must attach a dispensary label

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The selection of packaging for a pharmaceutical product
is dependent on the following factors

 The nature of the product itself: its chemical activity, sensitivity to

moisture and oxygen, compatibility with packaging materials
 The type of patient: is it to be used by an elderly or arthritic
patient, by a child?
 The dosage form

 Method of administering the medication etc.

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 Parts of packaging
 Container: is a device in which a drug is placed and it has a
direct contact with the product
 Closure: is a device which seals a container in order to
exclude oxygen, moisture, CO2 and microorganisms and
prevent the loss of medicament during transport and handling
 Carton: is the outer covering which give secondary protection
against mechanical and other environmental hazards
 Box: is generally used for packing multiples of product is
primary defense against hazards
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 Ideal characteristics of container and closure:
 Should be strong enough to withstand the handling, feeling, closing,
labeling and storage
 Inert
 Do not allow any loss of product
 Able to withstand heat
 Shouldn’t impart its color and odor to the preparation
 Should be able to protect light sensitive drug from light
 Easy to remove and replace
 Shouldn’t be expensive
 Attractive in appearance and acceptable to the consumer 20
 Glass:
Glass has several advantages among which are:
 It is inert to most medicinal products
 It is impervious to air and moisture
 It allows easy inspection of the container contents
 It can be colored to protect contents from harmful wave-
lengths of light
 It is easy to clean and sterilize by heat
 It is available in variously shaped containers
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 Glass…
 The disadvantages of glass are:
 It is fragile: glass fragments can be released into the
product during transport or contaminants can penetrate the
product by way of cracks in the container
 Certain types of glass release alkali into the container
contents
 It is expensive when compared to the price of plastic
 It is heavy resulting in increased transport cost

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 Glass…
 Depending upon the chemical constitutions of the glass and its ability to
resist deterioration.

There are four categories of glass packaging

Type I glass: this is also known as neutral glass or borosilicate glass.
 It possesses a high hydrolytic resistance due to its chemical composition.

 It is the most inert type of pharmaceutical glass with the lowest

coefficient of thermal expansion.
 As a result is it unlikely to crack on exposure to rapid temperature
changes.

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 Glass…
 It is suitable for packing all pharmaceutical preparations.
 However it is expensive and this restricts its applications for
ampoules and vials to package fluids for injection.
 used to package solutions that could dissolve basic oxides in
the glass.
 This would increase the pH of the formulation and could affect the
drug stability and potency.

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Glass…
Type II glass:
 made of soda-lime with a high hydrolytic resistance due to
surface treatment of the glass.
 used to package aqueous preparations.
 is not used to package parentrals with a pH less than 7.

 has a lower melting point than type I glass.

 easier to produce and consequently cheaper.
 used to produce containers for eye preparations and other
dropper bottles.
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Glass…
Type III glass:
 this is made of a soda-lime-silica glass.
 It has a similar composition to Type II glass but contains more
leachable oxides.
 It offers only moderate resistance to leaching and is commonly
used to produce dispensary metric medical bottles.
 also suitable for packaging non-aqueous parenteral products
and powders for injection.

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 Glass…
Type IV glass:
 this is made of a soda-lime-silica glass with a low hydrolytic
resistance.
 This glass must not be used to package parenteral products.
 Used for packaging solid, liquid and semi-solid formulations.

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 Types of Glass Containers:
Bottles:
 there are two main types of these (both are available in sizes from
50ml to 500ml and are supplied with a screw closure):
 The amber metric medical bottles: have a smooth curved side
and a flat side (to allow for a label).

 used for packaging oral medicines

 Ribbed (fluted) oval bottles: have flutes down one side of the
container as a sign for the user that the contents are not to be
taken or are for external use only.

 Products to be packaged in such bottles include:

liniments, lotions, inhalations and antiseptic solutions.
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Types of Glass Containers…

Dropper Bottles: hexagonal shaped amber glass

containers
 They are commonly used for eye drop and dropper

bottles for ear and nasal use.

Jars: powders and semisolid preparations are

generally packed in wide mouthed cylindrical jars

made of clear or amber glass.

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 Types of Glass Containers…

Containers for Parentral Products: glass ampoules are used to

package parentral solutions intended for single use.

Multiple-dose vials are used to package parenteral formulations

that will be used on more than one occasion.
Here Type I glass is widely made use of

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 B. Plastics
 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.

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 Plastics…
 Plastic containers are used for many types of pack including
rigid bottles for tablets and capsules, squeezable bottles for
eye drops and nasal sprays, jars, flexible tubes, strip and
blister packs.
 The composition and the physical shape of the containers
vary widely to suit the application

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 Plastics…

 Two classes of plastics are used in the packaging of

pharmaceutical products. These are:
 Thermosets are used for making screw caps for glass

and metal containers.

 Thermoplastics polymers are used in the manufacture of a
wide variety of pharmaceutical packages

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The advantages of plastics for packaging

 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
 easily moulded in to various shapes

 suitable for use as container, closure and as secondary packaging

 Are cheap

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The disadvantages of plastics
are not as chemicsally inert as type I glass
Some plastics undergo stress cracking and distortion form
contact with some chemicals

Some plastics are very heat sensitive

are not as impermeable to gas and vapor as glass
may possess an electrostatic charge which will attract particles
Substances such as the active drug and preservatives may be
taken up from the product

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 The principal plastic materials used in
pharmaceutical packaging

• Polyethylene:

Is used as high and low density polyethylene.

• The low density (LDPE) is softer and more easily
stretched (preferred for squeeze bottles) than high
density polyethylene (HDPE).
• HDPE is widely used in bottles for solid dosage forms

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 The principal plastic materials…
Polyvinyl chloride (PVC):
 Is obtained by adding a chlorine atom to every other carbon
in the polyethylene polymer.
 extensively used as rigid packaging material

for blister packaging of tablets and capsules and

as the main component of intravenous bags.

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The principal plastic materials…
Polypropylene:
when methyl groups are added to every other carbon atom
in the polymer chains of polyethylene we will get
polypropylene
Is a material which can be effectively autoclaved while
polyethylene cannot.
 It has a good resistance to cracking when flexed.

has been used as tablet containers and intravenous bottles.

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 The principal plastic materials…
Polystyrene:
a long chain hydrocarbon with every other carbon connected to a
phenyl group
is a clear hard brittle material with low impact resistance.
Its use in drug packaging is limited due to its high permeability to
water vapor.
used for tubes and amber-tinted bottles where clarity and stiffness
are important and high gas permeability is not a drawback.
used for jars for ointments and creams with low water content.
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 The principal plastic materials…
Tamper evident closures:
 such closures indicate if unlawful access to the contents of
the container has occurred and are currently available in
various designs suitable for different containers and closures.

 The most widely used type of tamper evident closures utilize

either a white polypropylene or LDPE

 Tamper evident inner seals are also there positioned within

the closure and are attached to the rim of the opening to the
container isolating its contents.

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 The principal plastic materials…
Compliance Packaging

To assist patients in taking their medications on schedule,

manufacturers and pharmacists have devised different

ways among which are compliance packages.

– The oral contraceptive compact type plastic package

was among the earliest product packages developed.

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The principal plastic materials…
–For prescriptions dispensed in traditional containers, pharmacists may

provide individualized calendar medication schedules or

commercially available devices for the daily or weekly scheduling of

dosage units.

–Theses techniques are particularly useful for patients taking multiple

medications.

–Electronic compliance packaging systems are also available

nowadays.

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C. Paper

Paper is used more than any 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

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D. Metal
Unbreakable
Aluminum, Tin, Tin pleated steel, Stainless steel, Lead are
used in the preparation of container
Tin is used for packaging of foods and certain pharmaceutical
and it is inert
Al= collapsible tubes are made, light in weight and has low
cost
– Used for ointment packaging
Lead= used for manufacture of envelop dispensing tablets and
capsules

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Labeling Pharmaceuticals
The label on dispensed medicines has two main functions.
– Uniquely identify the contents of the container.
– 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.
– The pharmacist has both legal and professional requirements
which must be complied with when labeling a dispensed
medicine.

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 Standard Requirements for Labeling Dispensed
Medicines
The details which must appear on the label of a dispensed
medicine are:
The name of the preparation and the quantity:
– the preparation may be prescribed generically but only be available as
a proprietary or branded product;
– however, the prescribed name must be used to avoid patient confusion.
– the quantity written could be the quantity of the drug prescribed or the
quantity in the container.
– If the preparation is available in more than one strength, the strength
must be included on the label.

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Standard Requirements…

Instructions to the patient: this should give information

on how much, how often and how to use the medicine.
The patient’s name

The date of dispensing

The name and address of the pharmacy
‘Keep out of reach of children

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Additional Labeling 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. diluted preparation
Additional legal requirements

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 Additional Labeling Requirements…

Over the counter package labeling must include:

 appropriate warning statements whenever the medication
is such that indiscriminate use may lead to serious medical
complications or mask a condition more serious than that
for which the medication was intended.
 The label must be perfectly clear in meaning

According to federal regulations in the US, drug labeling

includes not only the labels placed on the immediate container
and packaging, but also the package inserts accompanying the
product as well as all company literature and advertising or
promotional material pertaining to the drug product.

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Additional Labeling Requirements…

The essential information on a prescription only drug is generally

provided to the health professional through the product’s package
insert.

This insert must provide full disclosure that it must contain:

• Description of the product, including proprietary and non-
proprietary names of the drugs present
• Clinical pharmacology

• Indications and usage

• Contraindications
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Additional Labeling Requirements…
• Warnings/Precautions
• Adverse reaction
• Drug abuse and dependence potential

• Over dosage signs and treatment

• Dosage and administration
• Dosage forms, strength and package sizes supplied

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 The Ethiopian Case:
 According to the standards for the establishment and practice of
pharmaceutical compounding laboratory by the former Drug
Administration and Control Authority (DACA) of Ethiopia, The
label on bulk preparations shall bear the following:

Name of the product

Date of preparation

Batch number

Volume /weight/ of the preparation

Name and address of the compounding institution

Storage condition
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 The Ethiopian Case…

 Labels on compounded products for individual patient shall

have the following information:
Name of Patient and Address
Quantity of each ingredient used
Dose and administration
Storage condition
Name and Address of the compounding institution
Volume or total weight
Date of preparation

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 Freshly and Recently Prepared

 The direction, given under the side-heading extemporaneous

Preparation in British Pharmacopoeia, that a preparation must
be freshly prepared indicates that it must be made not more
than 24 hours before it is issued for use.
 The direction that a preparation should be recently prepared
indicates that deterioration is likely if the preparation is stored
for longer than about 4 weeks at 15°c to 25°c.

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 Storage
 To insure the stability of a pharmaceutical preparation for the period of its
intended shelf life, the product must be stored under proper conditions.
 The terms generally employed in such labeling have meanings defined by
the official compendia:
 Cold: any temperature not exceeding 8oc.

– A refrigerator is a cold place in which the temperature is maintained

thermostatically between 2 and 8.
– A freezer is a cold place in which the temperature is maintained
thermostatically between -10 and -20

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 Storage…
 Cool: any temperature between 8oc and 15oc.

– An article for which storage in a cool place is directed may

alternatively be stored in a refrigerator unless otherwise specified in
the individual monograph.
 Room temperature: the temperature prevailing in working area.

– A controlled room temperature encompasses the usual working

environment of 20oc to 25oc
– It allows also for temperature variations between 15 oc and 30oc that
may be experienced in pharmacies, hospitals, and drug warehouses.

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 Storage…
 Warm: any temperature between 30oc and 40oc.

 Excessive Heat: any temperature above 40oc.

 Protection from Freezing: where in addition to the risk of

breakage of the container, freezing subjects a product to
loss of strength or potency or to destructive alteration of
the dosage form, the container label bears an appropriate
instruction to protect the product from freezing.

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 Storage…
 When no specific storage or limitations are provided, it is
understood that the storage conditions include protection from
moisture, freezing and excessive heat.

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 Beyond Use Dating for Compounded
Preparations
 There is a difference in terminology between an expiration
date and a beyond use date.
– An expiration date is a projection of the length of time the
product can be expected to retain its purity and potency
based on accelerated stability studies.
• Expiration dates are used for commercial products.

– A beyond use date is an estimate of the time interval that

the compounded preparation can be expected to retain its
purity and potency based on general guidelines, literature
references, or actual real time stability studies using
prescribed conditions

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Beyond Use Dating…
 In general a maximum beyond use date of 6 months is
used.
 Unless published data are available to the contrary, the
following are the maximum recommended beyond use
dates for non-sterile compounded drug preparations that are
packaged in tight, light resistant containers when stored at
a controlled room temperature or as otherwise indicated

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 Beyond Use Dating…

 Non-aqueous liquids and solid formulation:

– if the source of the ingredients is a manufactured drug

product, the beyond use date should be no later than 25%
of the time remaining on the original product’s expiration
date, or 6 months whichever is earlier.
– If the source of the ingredients is a USP/NF substance the
beyond use date is no later than 6 months.

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 Beyond Use Dating…

 Water containing formulations:

 when prepared from ingredients in solid form the beyond use
date should be no later than 14 days when stored at cold
temperatures
 All other formulations:
 in all other instances, the earlier of 30 days or the intended
duration of therapy should be used. The beyond use date
limits may be exceeded in case of valid data.
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