Layout of this text:

Accurate and effective pharmaceutical formulation is a key skill which must be mastered
by all student pharmacists and pharmaceutical technicians. This book is intended to be a
guide to assist the student compounder in practicing exercises relating to the key dosage
forms encountered within extemporaneous dispensing.
The book has been designed as a stand-alone revision text and summarizes the key points
behind the manufacture of common extemporaneous dosage forms, along with a series of
worked examples and questions (with answers) for students to use for self-learning. Each
chapter is set out as follows:
1. A chapter overview box summarizing the key points covered in the chapter.
2. An introduction and overview of the product type.
3. A general method for the preparation of the product type.
4. A collection of worked examples to aid understanding and to include details on suitable
labelling and packaging.
5. A series of self-assessment questions which it is expected that the student would work through
independently. The answers to the questions can be found at the end of the book.
When a prescription is received for an extemporaneous product, there are a number of
considerations to be made prior to dispensing. Within each chapter, the worked examples
section will take a number of different preparations and expand on their compounding
using the following subheadings:
1. Use of the product
2. Is it safe and suitable for the intended purpose?
3. Calculation of formula for preparation
4. Method of preparation
a) Solubility where applicable
b) Vehicle/diluent
c) Preservative
d) Flavouring when appropriate
5. Choice of container
6. Labelling considerations
a) Title
b) Quantitative particulars
c) Product-specific cautions (or additional labelling requirements)
d) Directions to patient – interpretation of Latin abbreviations where necessary
e) Recommended British National Formulary cautions when suitable.
f) Discard date.
 g) Sample label (you can assume that the name and address of the pharmacy and the
words Keep out of the reach of children’ are pre-printed on the label)
7. Advice to patient.
In all the worked examples, the information provided in this text has been fully referenced.
Wherever possible, the following reference texts have been used:
✓ British Pharmacopoeia (2004, London: TSO).
✓ British National Formulary, 51st edn (2006, London: BMJ Publishing Group and RPS
Publishing).
✓ Martindale, The Extra Pharmacopoeia, 33rd edn (London: Royal Pharmaceutical
Society).
For some information (e.g. solubility data) it has been necessary to use older reference
sources. Where this has happened, details of the references used have been fully annotated
within the text. However, it should always be remembered that wherever possible,
compounders should use the most up-to-date reference source available.
In addition to the product-type chapters, this chapter contains a summary of the key storage,
labelling and packaging requirements for extemporaneous dosage forms.

Overview:
Upon completion of this chapter, you should be able to:
✓ understand the key principles behind labelling of pharmaceutical preparations
including:
o How to label products for both internal and external use.
o The importance of auxiliary labels.
o The rationale behind choosing an appropriate discard date.
✓ identify the different pharmaceutical packaging available.
✓ select appropriate packaging for different pharmaceutical formulations.
Storage and labelling requirements:
Storage All products dispensed extemporaneously require
some form of additional storage instructions to be detailed on
the label. This information can be the addition of just a product
expiry date through to a number of important additional
auxiliary labels.
The summary list given in Table 1.1 is to be used as a guide
in the absence of any guidance from the official
pharmaceutical texts. It should be remembered that the
information in this table is to be used only as a guide. Any
information on additional labelling or expiry dates in the official texts will supersede the
information provided in Table 1.1.
All suggested expiry dates included in Table 1.1 and other sections of
this book are to be used as a guide only and are based on historical
practice.
General principles of labelling:
Every extemporaneously prepared preparation will require a label to
be produced before the product can be dispensed or sold to the patient.
The accuracy of the label is paramount as it conveys essential
information to the patient on the use of the preparation.
Although the pharmacist or other healthcare practitioner may counsel
patients when the medication is handed over, it is unlikely that patients
will be able to remember all the information that they are given
verbally. The label therefore acts as a permanent reminder of the key
points that patients need to know.
Table 1.1: A guide to auxiliary labels and discard dates for extemporaneous
Appearance:
✓ Correct position:
Medicine bottles: The label should be on the front of a medicine bottle about a third
of the way down the container. The front of an internal bottle is the curved side and
the front of a fluted bottle is the plain side.
Cartons: The label should be placed on the large side of the carton. If there is not
enough room on a single side of the carton for the entire label, it should be placed
around the carton, ensuring that all the information is visible.
Ointment jars: The label should be placed on the side of the jar, ensuring that the
contents of the label are visible when the top is placed on the jar.
Ensure that the patient can open the container without destroying the label (e.g.
when labelling cartons).
Ensure the label is positioned with care and is straight, not crooked.
✓ Clean:
Ensure the container is clean before packing the product, then clean the outside
before affixing the label. Never pour any liquids into a pre-labelled container as this
risks spoiling the label with drips of the medicament.
✓ Secure:
Ensure that the label is secure before dispensing the product to the patient. The main
reason for labels not sticking to product containers is because of a dirty or greasy
container.
Information:
✓ Legible:
Always check label print size and quality to ensure that it can be read clearly. If there
is too much information to place on one label, consider placing the additional
information on a secondary label, rather than reducing the size of the print or trying
to include too much information on one label.
✓ Concise:
Although it is important that sufficient information is placed on the label, it must be
remembered that it is important not to confuse the patient by placing too much
information on the label. If the label contains too much information, rather than
assisting patients, they may feel overwhelmed and as a result they may read none of
the information.
✓ Adequate:
Ensure that sufficient information is given. For example, the term ‘when required’
raises the question how much? How often? When required for what?
✓ Intelligible:
The wording of the information on the label must be in plain English, be easily
understandable and use unambiguous terms. It must always be remembered that
patients may feel embarrassed to ask for further clarification on the meaning of
 complicated words used on the label.
✓ Accurate:
It is important that the title is accurate, the instructions are accurate and that the
patient’s name is complete and accurate.
Dispensed type labels:
In the UK, detailed requirements for labelling of medicinal products are contained in the
Medicines Act 1968 and in amendments to that Act made by Statutory Instrument. The
legislation distinguishes between labelling of a medicinal product for sale and labelling for
a dispensed product when lesser requirements apply.
1) All labels for dispensed medicines must have the name of the patient – preferably the full
name, not just initials – and if possible, the title of the patient (Mr, Mrs, Miss, Master, Ms
etc.) as this helps to distinguish between family members. The date and the name and
address of the pharmacy are also legally required. This will normally automatically
appear on most computer labelling systems with the date being reset automatically. The
words ‘Keep out of the reach of children’ are also legally required, but most labels used
for dispensing purposes are already pre-printed with these
words.
2) All labels must state the name of the product dispensed,
the strength where appropriate, and the quantity
dispensed.
3a) Products for internal use
The title of an extemporaneous preparation should be given
if it is an official product (i.e. one with an accepted formula
that can be found in an official text). The title should be
quoted in the official text (for example, ‘Ammonia and
Ipecacuanha Mixture BP’).
If it is an unofficial product (that is, a product made from an
individual formula, for example, a doctor’s own formula) it
may be labelled ‘The Mixture’ or ‘The Solution’ etc.
Unofficial products must state the full quantitative particulars
on the label (i.e. the formula must be stated on the label). For
preparations intended for internal use, this is expressed as the
amount of ingredient per unit dose.
For example, the quantitative particulars for a Sodium
Chloride BP solution 4% with a dose of 10 ml bd could be labelled as:

The Solution
Each 10 ml dose contains:
Sodium Chloride BP 400 mg
Freshly boiled and cooled purified water to 10 ml
3b) Products for external use:
Labels for preparations not intended for oral use require slightly different labelling. If the
product being made is official, the official title should be used (e.g. ‘Sodium Bicarbonate Ear
Drops BP’ or ‘Sodium Chloride Mouthwash BP’).
If the product is an unofficial product the label title may reflect the type of external product:
e.g.
‘The Nose Drops’
‘The Ear Drops’
‘The Mouthwash’
‘The Lotion’
‘The Enema’ etc.
As with preparations intended for oral use, unofficial products for external use need to be
labelled with the full quantitative particulars. In the case of products for external use, the
quantitative particulars are expressed as the complete formula.
Therefore, the quantitative particulars for 100 ml Sodium Chloride BP Lotion 4% would be
labelled:

The Lotion
Containing:
Sodium Chloride BP 4g
Freshly boiled and cooled purified water to 100 ml

Or
The Lotion
Containing:
Sodium Chloride BP 4%
Freshly boiled and cooled purified water to 100%

Similarly, the quantitative particulars for 200 ml of Sodium Chloride BP Lotion 4% would
be labelled:

The Lotion
Containing:
Sodium Chloride BP 8g
Freshly boiled and cooled purified water to 200 ml

Or
The Lotion
Containing:
Sodium Chloride BP 4%
Freshly boiled and cooled purified water to 100%

4) Labels must also include an expiry date. See Table 1.1 for guidance. The Medicines
Act 1968 (as amended) requires medicinal products to specify a month and year after
which the product should not be used. However, in practice this can cause confusion
and an alternative format is to show expiry as a single discard date: for example,
‘Discard after 31.01.07’.
5) Warning labels may also be required. These may be pharmaceutical or pharmacological
warnings (see labelling appendix in the British National Formulary). Generally, if there
is a choice between two warning labels with equivalent meaning, the positive one
should be chosen (e.g. ‘For rectal use only’ is preferable to ‘Do not swallow’ for
suppositories).
Table 1.1 gives guidance on the use of additional auxiliary labels. Within the UK, the
term ‘For external use only’ is used on any preparation intended for external use. The
Medicines Act 1968 defines products for external use as embrocation’s, liniments,
lotions, liquid antiseptics, other liquids or gels for external use.
However, traditionally, for the following dosage forms, alternative
labels have been employed instead of ‘For external use only’ to
reflect more closely the intended purpose of the product. These
alternative labels are (indicated on Table 1.1 by ‘*’):
▪ Enemas: ‘For rectal use only.’
▪ Gargles and mouthwashes: ‘Not to be taken.’
▪ Inhalations: ‘Not to be taken.’
▪ Nasal drops: ‘Not to be taken.’
▪ Pessaries: ‘For vaginal use only’
▪ Suppositories: ‘For rectal use only’.
Pharmacists should use their professional judgement when
deciding which auxiliary labels should be applied to different
pharmaceutical dosage forms. As it is accepted practice within the
UK to use the terms outlined above, these will be the terms used
within each of the product chapters.
6) All directions on labels should use active rather than passive
verbs. For example, ‘Take two’ (not ‘Two to be taken’), ‘Use
one’ (not ‘One to be used’), ‘Insert one’ (not ‘One to be inserted’), etc.
7) Where possible, adjacent numbers should be separated by the formulation name. For
example, ‘Take two or three times a day’ could allow for easy misinterpretation by the
 patient. Therefore, ideally, the wording on this label would include the formulation, e.g.
‘Take two tablets three times a day’. The frequency and quantity of individual doses are
always expressed as words rather than numerals (i.e. ‘two’ not ‘2’).
8) Liquid preparations for internal use usually have their dose expressed as a certain number
of 5 ml doses. This is because a 5 ml spoon is the normal unit provided to patients to
measure their dose from the dispensed bottle. Therefore, if a prescription called for the
dosage instruction 10 ml tds, this would be expressed as ‘Take two 5 ml spoonful’s three
times a day’. Pediatric prescriptions may ask for a 2.5 ml dose: in this case, the label
would read ‘Give a 2.5 ml dose using the oral syringe provided’. Note here the use of the
word ‘Give’, as the preparation is for a child and would be given to the patient by the
parent or guardian.
9) Remember the label on a medicine is included so that the item can be identified, and the
patient instructed as to the directions for use. Therefore, simple language should always
be used.
Never use the word ‘Take’ on a preparation that is not
intended for the oral route of administration.
Use ‘Give’ as a dosage instruction on products for children
as a responsible adult should administer them.
Only use numerals when quoting the number of milliliters
to be given or taken. All other dosage instructions should
use words in preference to numerals.
Always be prepared to give the patient a verbal explanation
of the label.
Pharmaceutical packaging:
All dispensed medicinal products will need to be dispensed to the
patient in a suitable product container. The function of a container
for a medicinal product is to maintain the quality, safety and
stability of its contents.
Although different pharmaceutical
preparations will be packaged in different
containers depending on the product type, pharmaceutical packaging
can largely be grouped into a few main types.
Tablet bottles:
Tablet bottles come in a variety of shapes and sizes and are usually
made of either glass or plastic (Figure 1.1). Generally, tablet bottles are
colored amber to reduce the likelihood of the contents reacting with
light. They are used for solid, single-dose preparations that are intended
for oral use (i.e. tablets and capsules).
In normal circumstances, all tablet bottles would be fitted with child-
resistant closures. Although not child-proof, these closures reduce the
possibility of access to medication by children. There are a number of different types of child-
resistant closures on the market. Consideration should be given to the patient when using
child-resistant closures, as some patient groups (e.g. the elderly and arthritic patients) may
not be able to open the container to access their medication. This can lead to non-compliance
or reduced compliance.

Figure 1.1: A selection of tablet bottles

Medical bottles
Plain amber medicine bottles:
Plain amber medicine bottles can be used to package all internal liquid preparations.
Traditional amber medicine bottles used in the UK have two different sides, one
curved and one flat (Figure 1.2). The label or labels are usually placed on the curved
side of the bottle as the patient’s natural action will be to pick the bottle up with the
curved side of the bottle facing the inside of the palm. By placing the label on the
curved side, this will mean the label is on the upper side of the bottle when in use.
This will prevent the label becoming damaged by any dribbles of liquid running
down the side of the bottle during pouring of a dose.

Figure 1.2: A selection of plain amber medicine

Plain amber medicine bottles come in a variety of sizes. The capacity of each bottle
is traditionally marked on the bottom of the container in milliliters. In the UK, plain
amber medicine bottles come in the following sizes: 50 ml, 100 ml, 150 ml, 200 ml,
300 ml and 500 ml.
As with tablet bottles (see above), child-resistant closures should be employed
whenever possible.
Fluted amber medicine bottles:
Fluted (or ribbed) amber medicine bottles are similar to the plain amber medicine
bottles but, instead of having a flat plain side, this side is curved and contains a number
of ridges or grooves running from the top of the bottle down to the bottom (Figure
1.3). The ridges or grooves are intended to be both a visual and tactile warning to the
patient or carer that the contents of the bottle are not to be administered via the oral
route (the tactile nature of the warning is particularly useful for blind or partially
sighted patients). For this reason, these types of containers are often referred to as
‘external medicine bottles’ or ‘poison bottles. There is a legal requirement (Medicines
Act 1968) in the UK that fluted bottles be used with specific types of pharmaceutical
preparations: embrocation’s, liniments, lotions, liquid antiseptics, other liquids or gels
for external use.

Figure 1.3: A selection of fluted amber medicine bottle

As with plain amber medicine bottles, the label is placed on the smooth curved side
of the bottle and the capacity of each bottle is traditionally marked on the bottom of
the container in milliliters. In the UK, fluted amber medicine bottles typically come
in the following sizes: 50 ml, 100 ml and 200 ml, although other sizes may be
available. Fluted dropper bottles are also available.
As with tablet bottles (see above), child-resistant closures should be employed
whenever possible.
Calibrated containers for liquid preparations:
Liquid preparations are normally made up to volume in a conical measure (Figure
1.4). There are occasions where a tared or calibrated bottle may be used. A tared bottle
 is normally only employed when, because of the viscosity of the final product, the
transference loss from the measure to the container would be unacceptable. For
example, Kaolin Mixture BP is a very dense suspension and transference may cause
problems; similarly, a thick emulsion will also prove difficult and time-consuming to
transfer in its entirety because of the viscosity of the finished product.

Figure 1.4: A selection of conical measures

Points to consider when taring a container:
✓ The volume of water added to the container to be tared must be identical to that of the
product being prepared and must be accurately measured using a conical measure.
✓ When poured into the container the meniscus is marked. (A simple method is to use a
small adhesive label to mark the position and thus produce a measure with just one
graduation.)
✓ The water is removed from the bottle and the bottle drained.
✓ The prepared mixture is transferred to the calibrated bottle, the measure or mortar used
in the preparation of the product is rinsed with more vehicle and this is added to the bottle.
✓ Any liquid ingredients are added, and the mixture is made up to volume using the vehicle.
✓ Remove the meniscus marker before dispensing the preparation to the patient.
Please note: unless the bottle is thoroughly dried after taring, this method can only be used
where water is one of the ingredients of the mixture as putting medicine into a wet bottle is
considered to be bad practice.
Cartons:
Cardboard cartons come in a variety of differing sizes, the sizes being dependent on the
manufacturer (Figure 1.5). They tend to be rectangular in shape and the label is placed on
the larger side of the box. They are used to package blister strips of tablets or capsules,
powder papers and other pharmaceutical products that may be of a shape that is not suitable
for labelling. Although it is good dispensing practice to label the primary container of a
medicinal product, in some cases this isn’t possible. By placing the primary container into a
labelled carton, this provides the next best method for labelling the product in question (for
example, the labelling of very small eye/ear/nose dropper bottles). Additional care must be
exercised in the storage of pharmaceutical products in cardboard cartons as they do not come
with child-resistant closures.

Figure 1.5: A selection of cartons.

Ointment jars:
Ointment jars come in a variety of different sizes and can be made of either colorless glass
or amber glass (Figure 1.6). Amber ointment jars are used for preparations that are sensitive
to light. They are used to package ointments and creams and can be used for individually
wrapped suppositories. As with cartons, additional care must be exercised in the storage of
preparations in ointment jars as they do not come with child-resistant closures.
Collapsible tubes:
Collapsible tubes come in a variety of different sizes and can be used to package creams or
ointments. They are less convenient to fill than ointment jars and as such are rarely used for
individual patient formulations. They are more commonly utilized in small scale
manufacturing environments where a number of identical product are being manufactured
at the same time. As with ointment jars, additional care must be exercised in the storage of
collapsible tubes as they do not come with child-resistant closures.
 Figure 1.6: A selection of ointment jars.
Standards for extemporaneous dispensing Patients who visit a pharmacy with a prescription
for a product needing to be extemporaneously prepared are entitled to expect the standards
within a pharmacy to be comparable to those of a licensed manufacturing unit. The products
produced within the pharmacy must be suitable for use, accurately prepared and prepared in
such a way as to ensure the products meet the required standard for quality assurance. So,
although this is small-scale production, the same careful attention to detail is required as
would be found in a manufacturing unit.
The following measures must be taken into consideration when preparing a product
extemporaneously:
✓ Personal hygiene. Personal hygiene is extremely important. Hygiene standards within a
pharmaceutical environment should be as high as, if not higher than, those found in food
kitchens. This is because within a pharmaceutical environment, medication is being
prepared for patients who may already be ill.
✓ Personal protective equipment. A clean white coat should be worn to protect the
compounder from the product and conversely the product from contamination from the
compounder. During the compounding process, safety glasses should always be worn
and, depending on the nature of the ingredients to be incorporated into the preparation,
additional safety equipment (e.g. face masks, gloves) may also be required. It is the
responsibility of the individual compounder to assess the risk posed by any
pharmaceutical ingredient and to ensure that the correct safety equipment is in use.
Similarly, long hair should be tied back, and hands washed, ensuring any open cuts are
covered.
✓ Clean work area and equipment. The cleanliness of the work area and equipment used
during the compounding procedure is of paramount importance. The risk of
contaminating the final product with either dirt or microorganisms from the surroundings
or from ingredients from a previous preparation can be considerable if attention is not
paid to the cleanliness of the work area and equipment. Before starting to compound a
product, the work area and equipment should be cleaned with a suitable solution (e.g.
 industrial denatured alcohol (IDA), formerly known as industrial methylated spirits
(IMS)), which must be allowed to dry fully.
✓ Work area. In addition to the cleanliness of the work area, consideration needs to be
given to the work area itself to ensure that it is suitable for its intended purpose. Both
lighting and ventilation need to be adequate. Some pharmaceutical ingredients are highly
volatile and so, if the ventilation within the work area was inadequate, this could cause
problems for the compounding staff.
✓ Label preparation. The label for any pharmaceutical product must be prepared before
starting the compounding procedure. This will enable the product to be labelled as soon
as it has been manufactured and packaged. This will eliminate a situation where an
unlabeled product is left on the bench and would reduce the possibility of the product
being mislabeled and given to the wrong patient.
✓ Weighing and measuring procedure. During weighing and measuring, unless strict
guidelines are followed, it can be very easy to mix up different pharmaceutical
ingredients as many ingredients resemble each other. It is preferable to incorporate a
weighed or measured ingredient into a product as soon as possible to prevent any
accidental switching. If this is not possible, when weighing or measuring more than one
ingredient, place each on a piece of labelled paper as soon as it has been weighed or
measured. This will avoid any accidental cross-over of ingredients.