Pharmaceutical Solutions

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 Solutions

Solutions are homogeneous liquid mixtures containing

completely dissolved components (One-phase system).

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 Solutions for ORAL dosage
Advantages of solutions over a solid DF:
•Much easier to swallow (i.e. Ease of taking e.g children, elderly,
chronic patients).
•Readily absorbed from GIT.

An advantage of solutions over suspensions:

•Solutions are homogenous dispersions without the need to
shake the bottle.

Disadvantages of solutions:
•Bulky, not convenient to carry around.
•Less chemically and microbiologically stable.
•Drugs with unpleasant taste may not be suitable for
administration as oral solutions.
•Accuracy of dosage depends on the patient.
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 Solutions for oral dosage
The different forms of oral solutions are:
• Syrups: which are concentrated, aqueous solutions of sugar or
sugar-substitute.
• Elixirs: which are clear, sweetened, hydroalcoholic solutions
suitable for water insoluble drugs.
• Linctuses: viscous liquids used in the treatment of cough. They
usually contain a high proportion of sucrose, other sugars or
polyhydric alcohol or alcohols.
• Mixtures: pharmaceutical oral solutions and suspensions.
Examples are chloral hydrate mixture.
• Oral drops: are oral solutions or suspensions which are
administered in small volumes, using a suitable measuring
device. A proprietary example is Abidec® vitamin drops.

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 Solutions for oral dosage
Containers for dispensed oral solutions:
•Plain, amber medicine bottles should be used, with a re-closable child-resistant
closure with some exceptions.
•A 5 mL measuring 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.

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 Solutions for other pharmaceutical uses
Mouthwashes and Gargles

• Gargles are used to relieve or treat sore throats

• 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, and usually diluted with
warm water before use.
• Gargles tend to contain higher concentrations of active
ingredients than mouthwashes.
• They may contain antiseptics, analgesics or weak
astringents. The liquid is usually not intended for
swallowing.
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 Solutions for other pharmaceutical uses
Mouthwashes and Gargles
Containers for mouthwashes and gargles
• An amber, ribbed bottle should be used for
extemporaneously prepared solutions. Medicine bottles
may be used for products which are intended to be
swallowed.
• Manufactured mouthwashes and gargles are usually
packed in plain bottles.

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 ”

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 Solutions for other pharmaceutical uses
Nasal solutions
• Most nasal preparations are solutions, administered as nasal
drops or nasal sprays.
• They are isotonic to nasal secretions 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.
• Nasal route may also be useful for new biologically active
peptides and polypeptides which need to avoid the first pass
metabolism or GI destruction.

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 Solutions for other pharmaceutical uses
Ear drops

• They may also be referred to as otic or aural

preparations.
• 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.
• Propylene glycol, oils, glycerol (to increase viscosity)
and water may be used as vehicles.

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 Solutions for other pharmaceutical uses
Nasal and aural solutions

Containers for nasal and aural preparations:

• Extemporaneously: should be packed in an amber,
ribbed hexagonal glass bottle (which type?) 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.

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 Solutions for other pharmaceutical uses
Nasal and aural solutions

Special labels and advice for nasal and aural prep:

•Not to share nasal sprays or nose and ear drops in order
to minimize contamination and infection.
•Patients should be given advice on how to administer
extemporaneously prepared nose and ear drops,
accompanied by written information if possible.
•Extemporaneous preparations should be labeled 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.
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 Solutions for other pharmaceutical uses
Enemas

• Enemas are oily or aqueous solutions that are administered

rectally.
• They are usually anti-inflammatory, purgative, sedative or given
to allow X-ray examination of the lower bowel.
• Retention enemas are administered to give either a local action
of the drug or for systemic absorption. They are used after
defecation.
• Microenemas are single-dose, small volume solutions. They are
packaged in plastic containers with a nozzle for insertion into
the rectum.
• Large-volume (0.5-1litre) enemas should be warmed to body
temperature before administration.

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 Solutions for other pharmaceutical uses
Enemas
Containers for enemas:
• If extemporaneously produced, enemas are packed in amber
fluted 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.

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EXPRESSION OF CONCENTRATION
• By percentage strength as %w/v or %v/v,
•In terms of amount of drug contained in 5 mL of vehicle.

FORMULATION OF SOLUTIONS
When compounding a solution:
•Information on solubility and stability of each of the
solutes ( drug, excipients) must be taken into account.
•Chemical and physical interactions that may take place
between constituents must also be taken into account.
e.g. Esters of p-hydroxybenzoic acid (parabens) with
some flavoring oils.
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 Solubility
Saturation solubility: is the maximum concentration of
a solution which may be prepared at a given
temperature.

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 Factors affecting solubility

• Polarity of the compound

• pH of the medium
• Temperature of solution
• Particle size may affect the rate of solution
Increasing the solubility
1. Co solvency: ethanol, glycerol, propylene glycol or sorbitol
are cosolvents used to increase the solubility of weak
electrolytes and non-polar molecules.
2. Solubilization: surfactants such as polysorbates for oral
solutions, soaps for external phenolic preparations.

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 Vehicles
• A vehicle is the medium which contains the ingredients of a
medicine. In solutions, this is the solvent.
• The choice of a vehicle depends on:
 The intended use of the preparation
 The nature and physicochemical properties of the active
ingredients.

Water as vehicle
• Water 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.

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 Vehicles
Water
Types of water:
• 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

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 Vehicle
Water
• 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. Aromatic waters are usually
prepared from a concentrated ethanolic solution, in a dilution of 1 part to 39
parts with water.

• Chloroform water is used as an antimicrobial preservative and also adds

sweetness to preparations.

 P.S. In general, chloroform can be available as:

 Chloroform BP = 100% v/v

 Concentrated chloroform water BPC = 10% v/v
 Single-strength chloroform water = Chloroform water BP= 0.25% v/v
 Double-strength chloroform water= 0.5% v/v

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 Other vehicles used in pharmaceutical solutions
• Syrup BP is a solution of 66.7% sucrose in water. Promotes dental
decay and is unsuitable for diabetic patients. Sweetening agents as
mannitol, sorbitol, xylitol, etc. can replace the sucrose to give 'sugar-
free' solvents.

• Alcohol rarely used for internal and mainly external

• Glycerol (glycerin) may be used alone as a vehicle in some external

preparations. It is viscous and miscible both with water and alcohol. It
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.

• Acetone and solvent ether used as cosolvents in external

preparation (limitations of ether).
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 Preservations of solutions

• Why preservation?
• Preservatives are added to the formulation to reduce or
prevent microbial growth.

Chloroform:
• Chloroform is the most widely used in oral extemporaneous
preparations although there are disadvantages to its use. Also
used for external preparations
• Use in general is limited to a chloroform content of 0.5% (w/w
or w/v).
• For oral solutions, chloroform at a strength of 0.25% v/v will
usually be incorporated as Chloroform Water BP.

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 Preservations of solutions
Other preservatives for oral solutions:
•Benzoic acid at a strength of 0.1% w/v
•Sorbic acid
•Para-hydroxybenzoate esters (Parabens).
•Ethanol
•Syrup: Syrups can be preserved by the maintenance of a high
concentration of sucrose 65% w/w .
•Some of the alternative preservatives have pH-dependent activity.
Preservatives for external preparations:
•Chlorocresol (0.1% w/v)
•Chlorbutanol (0.5% w/v)
•Parabens

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 Flavouring agents
• Why?

• Selection of flavours:
 To mask particular taste types, e.g. a fruit flavour helps to disguise an
acid taste.
 The age of the patient should be taken into account when selecting a
flavour, as children will tend to enjoy fruit or sweet flavours.
 Some flavours are associated with particular uses, e.g. peppermint is
associated with antacid preparations.
 The flavour and colour should also complement each other.

• Extemporaneous medicines tend to use natural flavours added as juices

(raspberry ), extracts (liquorice), spirits (lemon and orange), syrups
(blackcurrant), tinctures (ginger) and aromatic waters (anise and
cinnamon).

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 Sweetening agents

• Sugars, including glucose and sucrose.

• Sucrose enhances the viscosity of liquids and also gives
a pleasant texture in the mouth.
• ‘Sugar free’ solutions include sweetening agents such
as sorbitol, mannitol, xylitol, saccharin and aspartame
as alternatives to sugar (i.e. sucrose, fructose and
glucose).

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 Colouring agents
• Colouring agents are added to pharmaceutical preparations to
 Enhance the appearance of a preparation,
 Increase the acceptability of a preparation to the patient.
 Colour is also useful to give a consistent appearance.
 Colours are often matched to the flavour of a preparation.
 Colours can give distinctive appearances to some medicines.

• Colouring agents should be:

 Non-toxic .
 Free of any therapeutic activity themselves.

• Types of colouring agents:

 Natural colourants: derived from animals or plalnts (e.g. carotenoids, chlorophylls,
caramel, cochineal, saffron and red beetroot extract).
 Mineral pigments: such as iron oxide are not often used in solutions due to their low
water solubility.
 Synthetic organic dyes such as the azo compounds.

• Colours appear in pharmaceutical formulae less often now, especially in children's

medicines.

• In the EU, A EUROPEAN LIST OF COLOURING AGENTS HAVE THE DISIGNATION ‘E’ with
numbers between 100 and 180.
 Stabilizers
• Antioxidants may be used where ingredients
are liable to degradation by oxidation, e.g. in
oils.
• Those which are added to oral preparations
include:
 Ascorbic acid
 Citric acid
 Sodium meta bisulphite
 sodium sulphite.
• These are odourless, tasteless and non-toxic.

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 Viscosity enhancing agents

• Such as syrups, they improve viscosity,

palatability, and ease pourability.
• Other thickening agents can also be used.

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 Examples on solution preparations
• Ammonium and Ipecacuanha Mixture BP.
Mitte 100ml.
Master formula 100ml
Ammonium bicarbonate 200mg 2g
Liquorice liquid extract 0.5ml 5ml
Ipecacuanha tincture 0.3ml 3ml
Concentrated camphor water 0.1ml 1ml
Concentrated anise water 0.05ml 0.5ml
Double strength chloroform water 5ml 50ml
Water to 10ml to 100ml

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 Example on solution preparations
• Action and uses.
• Formulation notes.
• Method of preparation.
• Shelf life and storage.
• Advice and labeling.

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Rx 10 ml Sodium Bicarbonate Ear Drops BP.

Master
For
formula 10ml

Sodium bicarbonate 5g 500 mg

Glycerol 30 ml 3 ml
Water to 100ml to 10ml

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• 200ml Diamorphine linctus

Master formula for 200ml

Diamorphine
hydrochloride 3mg 120mg
Oxymel 1.25ml 50ml
Glycerol 1.25ml 50ml
Compound tartrazine
solution 0.06ml 2.4ml
Syrup to 5ml to 200ml

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• 50ml Chloral elixir, paediatric. For an 8-
month-old baby.

Master formula for 50ml

Chloral hydrate 200mg 2g
Water 0.1ml 1ml
Blackcurrant syrup 1ml 10ml
Syrup to 5ml to 50ml

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Rx Compound Sodium Chloride Mouthwash BP. Mitte 500ml

Master
For
formula 500ml
Sodium chloride 1.5g 7.5 g
Sodium bicarbonate 1g 5g
Concentrated peppermint emulsion 2.5ml 12.5ml
Double strength chloroform water 50ml 250ml
Water to 100ml to 500ml

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