2.

EXTEMPORANEOUS DISPENSING
OF:
SOLUTIONS
STUDY POINTS
Definitions of solutions and expressions of solubility
● Advantages and disadvantages of using solutions
● Methods of controlling solubility
● Selection of vehicles
● Use of preservatives and other ingredients in solutions
● Principles of dispensing:
Solutions for oral use
Diluents
Mouthwashes
Nasal
oral and aural solutions
Enemas
● Use of oral syringes
 INTRODUCTION
• Solutions are homogeneous mixtures of two or more components.
• They contain one or more solutes dissolved in one or more solvents, usually
solids dissolved in liquids.
• The solvent is often aqueous but can be oily, alcoholic or some other solvent.
 There are many types of pharmaceutical solutions.
 Solutions may be used as oral dosage forms, mouthwashes, gargles, nasal drops
and ear drops and externally as lotions, liniments, paints, etc.
 Solutions may also be used in injections and ophthalmic preparations
Advantages of solutions
•Easy to swallow
Liquids are much easier to swallow than tablets or capsules.
•Suitable for special patients
Ideal for children, elderly patients, and those with conditions like Parkinson’s disease who have
difficulty swallowing solids.
•Faster absorption
The medicament is already in dissolved form, so it is readily absorbed from the gastrointestinal
tract.
•Homogeneous distribution
The drug is evenly distributed throughout the solution, ensuring uniformity.
No need to shake
Unlike suspensions, solutions do not require shaking, making them more convenient.
•Accurate and consistent dosing
Because of uniform dispersion, solutions provide more consistent and reliable doses.
•Better patient compliance
Ease of use and swallowing improves patient acceptance and adherence.
•Ability to dissolve poorly soluble drugs
Drugs with low aqueous solubility can sometimes be formulated as solutions by adding co-
solvents, instead of making suspensions.
Disadvantages of solutions
• They are bulky, not convenient to carry.
• Less microbiologically and chemically stable than their solid
counterparts.
• Oral solutions may have an unpleasant taste.
• The accuracy of oral dosage is dependent on the patient
measuring the dose carefully.
The different forms of oral solutions are:
Syrups, which are aqueous solutions that contain sugar.
Elixirs, which are clear, flavoured liquids containing a high proportion of sucrose or a suitable
polyhydric alcohol and sometimes ethanol. Examples are phenobarbital elixir and chloral elixir
Linctuses, which are viscous liquids used in the treatment of cough. They usually contain a
high proportion of sucrose, other sugars or a suitable polyhydric alcohol or alcohols. Examples
are Simple Linctus BP and diamorphine linctus
Mixtures is a term often used to describe pharmaceutical oral solutions and suspensions.
Examples are chloral hydrate mixture and ammonium and ipecacuanha mixture BP
Oral drops are oral solutions or suspensions which are administered in small volumes, using a
suitable measuring device. Example is vitamin drops
Containers for dispensed solutions for oral use
Plain, amber medicine bottles should be used, with a reclosable child-resistant
closure.
• Exceptions to this are: if the medicine is in an original pack or patient pack, if
there are no suitable child-resistant containers for a particular liquid preparation
or if the patient requests it, e.g. if they have severe arthritis in their hands.
• Advice to store away from children should then be given.
• A 5mL medicine spoon or an appropriate oral syringe should be supplied to the
patient
Special labels and advice for dispensed oral solutions
• An expiry date should appear on the label for extemporaneously prepared
solutions.
• Most ‘official’ mixtures and some oral solutions are freshly or recently prepared.
• ‘Official’ elixirs and linctuses and manufactured products are generally more
stable, unless diluted.
• Diluted products generally have a shorter shelf-life than the undiluted
preparation.
• Linctuses should be sipped and swallowed slowly, without the addition of water.
Solutions for other pharmaceutical uses
• Topical solutions for external use are considered .

• Some topical solutions are designed for use in body cavities, such as the nose, mouth and ear.
Mouthwashes and gargles
• Gargles are used to relieve or treat sore throats and mouthwashes are used on the
mucous membranes of the oral cavity, rather than the throat, to refresh and
mechanically clean the mouth.
• Both are concentrated solutions, although gargles tend to contain higher
concentrations of active ingredients than mouthwashes.
• Both are usually diluted with warm water before use.
• They may contain antiseptics, analgesics or weak astringents. The liquid is usually not
intended for swallowing.
Examples are Phenol Gargle BPC and Compound Sodium Chloride Mouthwash BP
Containers for mouthwashes and gargles

An amber medicine bottle should be used for these extemporaneously prepared solutions.

Special labels and advice for mouthwashes and gargles

• Directions for diluting the preparations should be given to the patient.

• If the preparation is not intended for swallowing, the following label is appropriate:

‘Not to be swallowed in large amounts’

Short question answers

[Link] type of bottle is used for oral solutions?

Q2. Why are these bottles used?
Q3. When can child-resistant caps be avoided?
Q4. Why is an expiry date important for extemporaneous solutions?
Q5. What happens when a solution is diluted?
Q6. How should linctuses be taken?
[Link] label is used for mouthwashes and gargles?
Short question answers
[Link] type of bottle is used for oral solutions?
👉 Amber medicine bottle.
Q2. Why are amber bottles used?
👉 To protect the medicine from light.
Q3. When can child-resistant caps be avoided?
👉 When the patient requests it or cannot open it (e.g., arthritis).
Q4. Why is an expiry date important for extemporaneous solutions?
👉 Because they have a short shelf-life.
Q5. What happens when a solution is diluted?
👉 Its shelf-life becomes shorter.
Q6. How should linctuses be taken?
👉 Sipped slowly without water.
[Link] label is used for mouthwashes and gargles?
👉 “Not to be swallowed in large amounts.
Nasal Preparations

Most nasal preparations are solutions. Administered as: Nose drops , Nasal sprays.
• They are usually formulated to be isotonic to nasal secretions (equivalent to 0.9%
normal saline) and buffered to the normal pH range of nasal fluids (pH 5.5–6.5) to
prevent damage to ciliary transport in the nose.
• The most frequent use of nose drops is as a decongestant for the common cold or to
administer local steroids for the treatment of allergic rhinitis.
Overuse Warning

• Excess use of topical decongestants can cause:Oedema (swelling) of nasal

mucosa

• Should be used only for: Short duration (about 4 days)

• Long-term use leads to: Rhinitis medicamentosa (rebound congestion)

Receptor desensitization =
The nose stops responding to the medicine
(the drug becomes less effective)
Nasal Route for Drug Delivery

Useful for biologically active peptides & polypeptides

Advantages: Avoids first-pass metabolism , Prevents destruction in gastrointestinal
tract
Nasal mucosa allows: Rapid absorption, Systemic effect

There are some products utilizing nasal delivery currently available on the market,
e.g. desmopressin (e.g. Desmospray®, DDAVP®), used in the treatment of pituitary
diabetes insipidus.
Accurate dosage is achieved using metered spray devices
Ear drops
• Ear drops are solutions of one or more active ingredient which exert a local
effect in the ear, e.g. by softening earwax or treating infection or inflammation.
• They may also be referred to as otic or aural preparations.
• Propylene glycol, oils, glycerol (to increase viscosity) and water may be used as
vehicles.
Examples are aluminium acetate ear drops, almond oil ear drops and Sodium
Bicarbonate Ear Drops BP
Containers for nasal and aural preparations

• Nose and ear drops that are prepared extemporaneously should be packed in an
amber, ribbed hexagonal glass bottle which is fitted with a teat and dropper.
• Manufactured nasal solutions may be packed in flexible plastic bottles which
deliver a fine spray to the nose when squeezed, or in a plain glass bottle with a
pump spray or dropper. Manufactured ear drops are usually packed in small glass
or plastic containers with a dropper.
Special labels and advice for nasal and aural preparations
• Patients should be advised not to share nasal sprays or nose and ear drops in
order to minimize contamination and infection.
• Manufactured nasal sprays and nose and ear drops will usually contain
instructions for administration.
• Patients should be given advice on how to administer extemporaneously
prepared nose and ear drops, accompanied by written information if possible
(Fig. 33.1)
• For ear drops, it may be easier for someone other than the patient to administer
the drops.
• If desired, the drops can be warmed by holding the bottle in the hands before
putting them in, but they must not be overheated.
• The ear lobe should be held up and back in adults, down and back in children, to
allow the medication to run in deeper.
• Extemporaneous preparations should be labelled with the appropriate expiry date
following the official monographs.
• ‘For external use’ is not an appropriate label and so ‘Not to be taken’ is advised’.
Enemas
• Oily or aqueous solutions that are administered rectally.
• Usually anti-inflammatory, purgative, sedative or given to allow X-ray
examination of the lower bowel.
• Examples are arachis oil enema and magnesium sulphate enema
• Packaged in plastic containers with a nozzle for insertion into the rectum.
• Enemas are packed in amber, glass bottles.
• Manufactured enemas will usually be packed in disposable polythene or
polyvinyl chloride bags sealed to a rectal nozzle.
Special labels and advice for enemas

• Patients should be advised on how to use the enema if they are self-

administering and the time that the product will take to work.

• The label ‘For rectal use only’ should be used.

Expression of concentration

Strengths of pharmaceutical solutions can be expressed in a number of ways.

The two most commonly used are in terms of amount of drug contained in 5mL of

vehicle or percentage strength (see Ch. 19)

Expressions of concentration

The metric system is the International System of Units (SI Units) for weight,

volume and length. The basic unit for weight is the kilogram (kg), the basic unit for

volume is the litre (L) and the basic unit of length is the metre (m). The prefix

‘milli’ indicates one-thousandth (10−3) and ‘micro’ one millionth (10−6).

In some countries, the avoirdupois (or imperial) system (pounds and ounces) is still

used in commerce and daily life. The imperial system of volume (pints and gallons)

is still a common system for commerce and household measurement.

Pharmacists need to know about these systems in order to avoid serious errors in

interpretation of prescriptions. It is important to be able to change between the

systems. Some conversion factors for the metric and avoirdupois systems are shown

in Box 19.1 (see Examples 19.1–19.3).

Short question answers

Q1. What tonicity is required for nasal solutions?

A
Q2. Why are nasal solutions buffered?
A
Q3. What happens on overuse of nasal decongestants?
A.
Q4. Why is the nasal route useful for peptides?
A.
Q5: What is the purpose of straightening the ear canal?
A:
Q6: What are Uses of enema?
Short question answers

Q1. What tonicity is required for nasal solutions?

A. Isotonic (0.9% normal saline).
Q2. Why are nasal solutions buffered?
A. To prevent damage to ciliary transport.
Q3. What happens on overuse of nasal decongestants?
A. Oedema and rebound congestion.
Q4. Why is the nasal route useful for peptides?
A. Avoids first-pass metabolism.
Q5: What is the purpose of straightening the ear canal?
A: To help the medication reach deeper into the ear.
Q6: What are Uses of enema?
Usually anti-inflammatory, purgative, sedative or given to allow X-ray examination of the lower
bowel
Formulation of solutions
Solutions comprise the medicinal agent in a solvent as well as any additional agents.
These additional agents are usually included to provide colour, flavour, sweetness or
stability to the formulation.
• Most solutions are now manufactured on a large scale although it may be
occasionally required to make up a solution extemporaneously.
• When compounding a solution, information on solubility and stability of each of
the solutes must be taken into account.
• Chemical and physical interactions that may take place between constituents must
also be taken into account, as these will affect the preparation’s stability or
potency.
• For example, esters of p-hydroxybenzoic acid, which can be used as preservatives
in oral solutions, have a tendency to partition into certain flavouring oils.
• This could reduce the effective concentration of the preservative agent in the
aqueous vehicle of the preparation to a level lower than that required for
preservative action.
Solubility
Solubilities are usually stated as the
number of parts of solvent (by
volume) that will dissolve one part (by
weight or volume) of the substance.
Vehicles
In pharmacy, the medium which contains the ingredients of a medicine is called the
vehicle. In solutions, this is the solvent.
The choice of a vehicle depends on the intended use of the preparation and on the
nature and physicochemical properties of the active ingredients.
Water as a vehicle
• Water is the vehicle used for most pharmaceutical preparations.
• It is widely available, relatively inexpensive, palatable and non-toxic for oral use
and non-irritant for external use.
• It is also a good solvent for many ionizable drugs. Different types of water are
available as outlined below:
● Potable water is drinking water, drawn freshly from a mains supply. It should be
palatable and safe for drinking. Its chemical composition may include mineral
impurities, which could react with drugs, e.g. the presence of calcium carbonate in
hard water
● Purified water is prepared from suitable potable water by distillation, by treatment
with ion exchange materials or by any other suitable treatment method such as
reverse osmosis. Distilled water is purified water that has been prepared by
distillation
• Water for preparations is potable or freshly boiled and cooled purified water,
which can be used in oral or external preparations which are not intended to be
sterile.
• The boiling removes dissolved oxygen and carbon dioxide from solution in the
water. Any stored water, for example drawn from a local storage tank, should not be
used because of the risk of contamination with microorganisms:
Water for injections is pyrogen-free distilled water, sterilized immediately after
collection and used for parenteral products
Aromatic waters are near-saturated aqueous solutions of volatile oils or other
aromatic or volatile substances, and are often used as a vehicle in oral solutions.
Some have a mild carminative action, e.g. dill. Aromatic waters are usually prepared
from a concentrated ethanolic solution, in a dilution of 1 part of concentrated water
with 39 parts of water. Chloroform water is used as an antimicrobial preservative and
also adds sweetness to preparations
Other vehicles used in pharmaceutical solutions
● Syrup BP is a solution of 66.7% sucrose in water. It will promote dental decay and
is unsuitable for diabetic patients. Hydrogenated glucose syrup, mannitol, sorbitol,
xylitol, etc. can replace the sucrose to give ‘sugar-free’ solvents
● Alcohol (ethyl alcohol, ethanol). Rarely used for internal preparations but is a
useful solvent for external preparations
● Glycerol (glycerin) may be used alone as a vehicle in some external preparations.
Viscous and miscible both with water and alcohol. May be added as a stabilizer and
sweetener in internal preparations. In concentrations above 20% v/v, it acts as a
preservative
Propylene glycol is a less viscous liquid and a better solvent than glycerol
Oils. Bland oils such as fractionated coconut oil and arachis oil may be used for fat-
soluble compounds, e.g. Calciferol Oral Solution BP. Care is required when
using nut oils due to hypersensitivity reactions
Acetone is used as a co-solvent in external preparations
Solvent ether can be used as a co-solvent in external preparations for preoperative
skin preparation. The extreme volatility of ether and risk of fire and explosion
limit its usefulness
Factors affecting solubility
Compounds that are predominantly non-polar tend to be more soluble in non-polar
solvents, such as chloroform or a vegetable oil. Polar compounds tend to be more
soluble in polar solvents, such as water and ethanol. The pH will also affect solubility
as many drugs are weak acids or bases. The ionized form of a compound will be the
most water soluble, therefore a weakly basic drug will be most soluble in an aqueous
solution that is acidic. Acid or alkali may therefore be added to manipulate solubility.
Most compounds are more soluble at higher temperatures. Particle size reduction will
increase the rate of solution.
Increasing the solution of compounds with low solubility

Co-solvency
The addition of co-solvents, such as ethanol, glycerol, propylene glycol or sorbitol,
can increase the solubility of weak electrolytes and non-polar molecules in water.
Solubilization
Surfactants may be used as solubilizing agents. Above the critical micelle
concentration (CMC), they form micelles which are used to help dissolve poorly
soluble compounds.
The dissolved compound may be in the centre of the micelle, adsorbed onto the
micelle surface, or sit at some intermediate point, depending on the polarity of the
compound. Examples of surfactants used in oral solutions are polysorbates, while
soaps are used to solubilize phenolic disinfectants for external use.
Cover From book (pages 318 and 319)
• Preservation of solutions.
• Additional ingredients
(Flavouring agents, Sweetening agents, Colouring agents, Stabilizer, Viscosity-
enhancing agents
Shelf-life of solutions
There may be individual variations, but most solutions which are prepared
extemporaneously should be freshly or recently prepared.
The data sheets should be consulted for information about particular manufactured
solutions and for storage conditions
Oral syringes
If fractional doses are prescribed for oral liquids, they should not be diluted, but an
oral syringe should be supplied with the dispensed oral liquid.
The standard 5mL or 10mL capacity oral syringe is marked in 0.2mL divisions to
measure fractional doses.