SOLUTIONS

Dextromethorphan Hydrobromide
(Antitussive)
Chlorpheniramine maleate (Histamine H1
antagonist)
Phenylephrine Hydrochloride (Decongestant)
 What is solution?

 Stable homogenous mixture of two or more components

One or more solute is dissolved in one or more solvents

Solvent is often aqueous but can also be oily or alcoholic

Formulations: --- oral dosage forms, mouthwashes, gargles, nasal

drops, ear drops or available for external applications
 FORMULATION OF SOLUTIONS

1. Solubility
2. Increasing solubility of compounds with low solubility
3. Expression of concentration
4. Vehicles
5. Preservation of solutions
 FORMULATION OF SOLUTIONS (Contd..)

1. Solubility

 Number of parts (by volume) that will dissolve one part of the
substance.

 Maximum concentration to which a solution maybe prepared

with a particular agent in a particular solvent

 Example
Potassium chloride is soluble in 2.8 to 3 parts of water.
1g of KCL will dissolve in 2.8 to 3 ml of water at room
temperature
Factors affecting solubility

Polarity of the solutes

Non polar compounds are more soluble in non polar solvents such
as chloroform.

Polar compounds are more soluble in polar solvents such as water

and ethanol.

 Ionization of the compound

Ionized form of a compound will be the most water soluble

Hence weakly basic drug will be most soluble in acidic solution

 Preparing the salt form of drugs with low solubility is an approach

to enhance solubility.

E.g Enalapril maleate is the maleate salt of enalapril

Salbutamol sulphate --- salt form of salbutamol

• Each 5ml contains Salbutamol Sulphate BP equivalent to 2 mg of

Salbutamol

Tetracycline hydrochloride --- salt form of tetracycline

Particle size reduction

Temperature – Most compounds

are more soluble at higher
temperatures

• Paracetamol dissolved in heated

Propylene glycol  PCM syrup
2. Methods of increasing solubility of compounds with low
solubility

1. Cosolvency

 Cosolvency refers to the effects of adding one or more solvents

(cosolvents), which are different from the existing solvent in a
solution, on the properties of the solution or behavior of the
solute.

 Addition of cosolvents as ethanol, glycerol, propylene glycol or

sorbitol. E.g Paracetamol (Poorly soluble in water)
 Aim is to increase solubility of weak electrolytes and non polar
molecules in water.

 They work by decreasing interfacial tension between the

hydrophobic solute and the aqueous environment
2. Solubilization

 Surfactants are used as solubilizing agents – Sodium Lauryl Sulfate

(SLS), Tween 80

 At the CMC (critical micelle concentration) dispersed surfactant

molecules in a liquid aggregate to form micelles of colloidal
dimensions.
Micelle --- Aggregate of
surfactant molecules
dispersed in a liquid

CMC -- concentration of
surfactants above which
micelles form
Increasing concentration
of surfactant in water
slowly forming a layer on
the surface and
eventually forming
micelles at or above the
CMC.
 In aqueous solution –--

Hydrophobic areas of solubilizing agent points towards centre of

the micelle

Hydrophilic area point towards solvent

For non polar solvent (e.g oil) --- reverse is true (i.e head/
hydrophilic part is towards centre of micelle and tail / hydrophobic
part is towards solvent)

Micelles are used to dissolve poorly soluble compounds

3. Expression of concentration

2 common ways of expressing concentration of pharmaceutical

solutions are:

 %w/v and %v/v

E.g A 2% w/v preparation contains 2g of a constituent in 100 ml of

preparation.

1% v/v preparation contains 1 ml of a constituent in 100 ml of

preparation
4. Vehicles
 Medium containing the ingredients of a medicine

Examples of different vehicles –

 Water

Widely available, relatively inert, inexpensive, palatable and

nontoxic vehicle for oral use and non irritant for external use.

Different types of water are available such as:

a) Potable water –

 Drinking water drawn from main supply

 Contains impurities that may react with medicaments
b)Purified water

 Potable water after distillation or after suitable treatment

procedures like ion exchange.

 Main features of Purified Water USP are as follows:

 It is prepared by distillation, ion exchange methods or by

reverse osmosis

 Must not be used for the preparation of parenteral

formulations

In the case of parenteral formulations Water for Injections BP

must be used
Water for preparations

 For preparations like E.g oral powdered preparations requiring

reconstitution (amoxicillin dry syrup) or external preparations
not intended to be sterile.

 Freshly boiled and cooled purified water

d) Water for injections

 Pyrogen free, distilled water, sterilized and used for parenteral

products.

e) Aromatic waters

Aromatic waters are saturated solutions of volatile oils (e.g. Rose

oil, peppermint oil) or other aromatic or volatile substances.

Used as pharmaceutical aid principally for perfuming and flavoring

the formulation

Some other uses of aromatic waters are:

 Rose water has an antioxidant activity --- water cleanses, tones
and protects skin from harmful environmental impacts

 Chloroform water has been used as preservative and also adds to

sweetness to preparations

 These preparations should be protected from sunlight due to the

presence of volatile constituent in the preparation.
 Other vehicles used in pharmaceutical solutions
a)Syrup
 Solution of sucrose in water

 Highly concentrated, aqueous solutions of sugar or a sugar

substitute that traditionally contain a flavouring agent, e.g. cherry
syrup, cocoa syrup, orange syrup, raspberry syrup

The major components of syrups are as follows:

 Purified water
 Sugar (sucrose) or sugar substitutes (artificial sweeteners)

 Can promote dental decay

 Unsuitable for diabetic patients

 Due to the inherent sweetness and moderately high viscosity of
these systems  addition of other sweetening agents and viscosity-
modifying agents is not required

 Other non-sucrose bases may replace traditional syrup  E.g

Sorbitol

 Sorbital Solution USP which contains 64% w/w sorbitol (a

polyhydric alcohol)

 More recently, many products have been formulated as medicated

sugar-free syrups due to the glycogenetic and cariogenic (causing
tooth decay) properties of sucrose.

 All medicinal products designed for administration to children and

to diabetic patients must be sugar-free.
 Syrup substitutes must therefore provide an equivalent sweetness,
viscosity and preservation to the original syrups

 To achieve these properties artificial sweeteners (typically saccharin

sodium, aspartame), non-glycogenetic viscosity modifiers (e.g.
methylcellulose, hydroxyethylcellulose) and preservatives (e.g.
sodium benzoate, benzoic acid and parahydroxybenzoate esters) are
included.
b) Alcohol
 Useful solvent for external preparations

 Commonly used as a co-solvent both as a single co-solvent and

with other co-solvents, e.g. glycerol

The known pharmacological and toxicological effects of this co-

solvent have compromised the use of alcohol in pharmaceutical
preparations

As a result there are labelling requirements for preparations that

contain alcohol
C) Glycerol

 Maybe used as vehicle for external preparations.

 Miscible with both water and alcohol

 Used as stabilizer (chemical which inhibit the reaction between two or

more other chemicals) and sweetner in internal preparations

 In concentration above 20% v/v – acts as a preservative

d) Oils
 Fractionated coconut oil and arachis oil (peanut oil) maybe used
for fat soluble compounds.eg Calciferol oral solution BP (Vitamin
D oral solution)

e) Propylene glycol

 Clear, colorless liquid with viscosity lower than of glycerol.

 It is hygroscopic (attracts water) and has low toxicity
 Used as a solvent for oral, injectable and topical formulations like
diazepam, lorazepam that are insoluble in water
 Used in pharmaceutical preparations as a co-solvent, generally as a
replacement for glycerin.
f) Acetone
 Used as a cosolvent in external preparations

g) Solvent ether
 Extreme volatility of ether and risk of fire and explosion limits its
usefulness as a cosolvent in external preparations
Preservation of solutions

 Preservatives are included in pharmaceutical solutions to

control the microbial bioburden of the formulation.

 Ideally preservatives should exhibit the following properties:

 Possess a broad spectrum of antimicrobial activity

encompassing Gram-positive and Gram-negative bacteria
and fungi

 Be chemically and physically stable over the shelf-life of the

product

 Have low toxicity

 Chloroform was used as preservative in oral preparations

 For oral solutions – chloroform is incorporated at strength of

0.25%v/v as chloroform water BP

 Disadvantages of chloroform use:

 High volatility
 Reported carcinogenecity in animals

 Benzoic acid at a strength of 0.1% w/v, ethanol, sorbic acid,

hydroxybenzoate esters are other examples  replaced the use
of chloroform
 Preservatives used in external solutions include ---

 Chlorocresol (0.1%w/v)
 Chlorbutol (0.5% w/v)
 Parahydroxybenzoates (Parabens)
SOLUTIONS FOR ORAL DOSAGE

Advantages of solutions over other dosage forms

Additional Ingredients
- Flavouring agents
- Sweetening agents
- Colouring agents
- Stabilizers
-Viscosity enhancing agents
Oral Syringes
Diluents
Containers for dispensed solutions for oral use
Specialized labels and advice for dispensed oral solutions
 SOLUTIONS FOR ORAL DOSAGE

Advantages of solutions over other dosage forms???

1. Advantages over solid dosage forms:

Medicament is readily absorbed into GIT

May be designed for any route of administration

Liquids are much easier to swallow than tablets or capsules

Especially advantageous for children, elderly or those with

chronic conditions such as Parkinsonism (swallowing difficulty)

 Those having difficulty swallowing solid dosage forms

 SOLUTIONS FOR ORAL DOSAGE

2. Advantages over Suspensions:

Medicament is dispersed homogenously throughout the

preparation --- No need to shake the bottle --- Easier to use for
patients
 SOLUTIONS FOR ORAL DOSAGE
3. Disadvantages of solutions
Bulky

Inconvenient to carry compared to solid dosage forms

Technical accuracy needed to measure dose on administration

Measuring device needed for administration

Less stable microbiologically and chemically than their solid

counterparts

Some drugs poorly soluble

Drugs not palatable may not be suitable candidate for

administration as oral solution
• Syrups – Aqueous solution containing sugar. E.g cyproheptadine
syrup, cetrizine syrup

• Elixirs – Clear flavoured liquids containing high proportion of

sucrose or suitable polyhydric alchohol and sometimes ethanol. E.g
phenobarbitone elixir

• Linctuses – Viscous liquids used in treating cough. Should be sipped

slowly and usually contain high proportion of sucrose or other sugars,
or suitable polyhydric alcohol. E.g Pholcodine linctus

• Mixtures – Term used to describe pharmaceutical oral solutions or

suspensions.

• Oral drops – Oral solutions/suspensions given in small volumes

using suitable measuring device. E.g vitamin drops
Additional Ingredients

Include excipeints such as flavouring agents, sweetening agents,

colouring agents etc.

Added to improve palatability and appearance of the solution to the

patient.
Flavouring agents

 Flavours are added to solutions to make a medicine more

palatable especially for drugs with unpleasant taste.

 Flavours can be chosen based on

 Taste of the drug

E.g Fruit flavor helps to disguise acid taste

 Age of patient
E.G Children tend to enjoy sweet or fruit flavours
 Some flavours are associated with particular uses
E.g Peppermint is associated with antacid preparations

Some examples of flavours used in pharmaceutical preparations --- Raspberry,

Peppermint, Cinnamon etc.

 Flavours that may be used to mask a salty taste include:

● butterscotch
● apricot
● peach
● vanilla
● wintergreen mint

 Flavours that may be used to mask a bitter taste include:

● cherry
● mint
● anise (saunf)
 Flavours that may be used to mask a sour taste include:
● citrus flavours
● raspberry

 The concentration of flavour in oral syrups is that which is required to provide

the required degree of taste-masking effectively

 Certain flavours are also associated with a (mild) therapeutic

activity

 E.g many antacids contain mint due to the carminative properties of this
ingredient
Sweetening agents

 Sucrose enhances viscosity of liquids as well as gives pleasant

texture in mouth.

 Disadvantage – Prolonged use may cause dental caries

 Alternative agent – Using sorbitol, mannitol, xylitol, saccharin as

sweetening agents instead of sugar.
Oral liquid preparations that do not contain fructose, sucrose or
glucose are labelled as “Sugar Free” in British National Formulary.

These alternatives should be used whenever possible

Colouring Agents

Added to pharmaceutical preparations to enhance appearance of

preparation or to increase acceptability to patient.

Colours are often matched to flavour of preparation

E.gYellow color for a banana flavoured preparation

Green with mint-flavoured solutions

 Red for strawberry-flavoured formulations

 Colour also used to give consistent appearance where there is natural
batch variation between materials.

 Can give distinctive appearance to some medicines

 Colouring agents should be non toxic and free of any therapeutic activity
themselves.

 Natural colourants (derived from plants and animals) e.g carotenoids,

red beetroot extract can be used.

-Variation in quality of different batches limits its use.

 Synthetic organic dyes such as azo compounds are alternatives for

colouring pharmaceutical solutions --- give bright and stable colours.
E.g tartrazine dye
Stabilizers

 Antioxidants are included in pharmaceutical solutions to enhance

the stability of therapeutic agents that are susceptible to chemical
degradation by oxidation

 Typically in aqueous solution antioxidants are oxidised (and hence

degraded) in preference to the therapeutic agent, thereby
protecting the drug from decomposition

Are odourless, tasteless and non toxic.

E.g ascorbic acid, citric acid, sodium metabisulphite

 E.g antioxidants for aqueous formulations include: sodium
sulphite, sodium
metabisulphite, sodium formaldehyde sulphoxylate and ascorbic acid

 Examples of antioxidants that may be used in oil-based solutions

include: butylated hydroxytoluene (BHT), butylated hydroxyanisole
(BHA) and propyl gallate

 Typically antioxidants are employed in low concentrations ( 0.2%

w/w)
Oral Syringes

 To administer fractional doses of

oral liquids

Oral syringe has divisions from

1 to 5 ml to measure doses of
less than 5 ml.

Instruction for use of oral syringe

(Refer Pg 114. Fig 11.1)
Containers for dispensed solution for oral use

Plain or amber bottles should be used with child resistant closure

Advice to store away from children should be given.

A 5ml measuring spoon or an appropriate oral syringe should be

supplied to the patient
Special labels and advice for dispensed oral solutions

Expiry date should appear on label for extemporaneously prepared

solutions.

Linctuses should be sipped and swallowed slowly without addition

of water

Direction of useTake two spoonful 5ml three times a day before

food
 SOLUTIONS FOR OTHER PHARMACEUTICAL USES

Mouthwashes and Gargles

Nasal solutions
Ear drops
Enemas
Mouthwashes and Gargles

Gargles are used to relieve or treat sore throat

Mouthwashes are used on mucous membranes of oral cavity rather

than on throat to refresh and clean mouth.

Both are concentrated solutions but gargles tend to contain higher

concentrations of active ingredients than are present in
mouthwashes.

 usually diluted with warm water before use

Should not be swallowed

May contain antiseptics, anlagesics
E.g Compound sodium chloride mouthwash BP
 Chlorhexidine Mouthwash
Povidone iodine mouthwash and gargle

Containers for mouthwashes and gargles

Manufactured mouthwashes and gargles are usually packed in plain

bottles

Special labels and advice

Directions for diluting should be given.
“Not to be swallowed in large amount” should be mentioned if the
preparation is not intended for swallowing
Nasal Solutions

Most nasal preparations are solutions – administered as nose drops

or sprays.

Isotonic to nasal secretions and buffered to normal pH range of

nasal fluids (pH 5.5-6.5) to prevent damage to ciliary transport in
nose.

Most common use:

 Decongestant for common cold

 To administer local steroids for treatment of allergic rhinitis
E.g Normal saline nose drops and ephedrine nose drops 0.5% or 1%.

Overuse of topical decongestants can lead to edema of the nasal

mucosa

Should be used only for short periods of time (about 5 days) to

avoid rebound congestion called as rhinitis medicamentosa.

Nasal route – useful route for new biologically active peptides and
polypeptides that need to avoid first pass metabolism and
destruction by gastrointestinal fluids.

E.g desmopression available as Desmospray used in treatment of

diabetes insipidus
Ear Drops

Solutions of one or more active ingredients that exert local effect in

ear.

E.g softening of earwax, treating infection or inflammation

Also referred to as Otic/ Aura preparations.

E.g ciprofloxacin ear drops etc.

Containers for nasal and aural preparations

Nose and ear drops prepared extemporaneously should be packed

in an amber, ribbed glass bottle fitted with a rubber teat and
dropper

Manufactured nasal solutions maybe packed in

flexible plastic bottles that deliver a fine spray
to nose when squeezed or in plain glass
bottle with a pump spray or dropper
Special labels and advice for nasal and aural preparations

Patients should be advised not to share nasal sprays or nose and ear
drops to minimize contamination and infection.

Patient should remain for few minutes after the drops have been
administered to allow medication to spread in the nose

For ear drops –

Ear lobe should be held up and back in adults and down and back in
children to allow the medication to open ear canal and allow
medicine to run deeper

May cause some transient stinging.

If the drops are used to soften ear wax – Ears are syringed after use

Extemporaneous preparations should be labelled with expiry date

“Not to be taken” should be written mentioned in the label

Enemas

Oily or aqueous solutions administered rectally.

Pharmaceutical solutions that are administered rectally and are

employed to ensure clearance of the bowel  usually by softening
the faeces or by increasing the amount of water in the large bowel
(osmotic laxatives)

Enemas may be aqueous or oil-based solutions

Aqueous formulations usually contain salts (e.g. phosphates) to alter

the osmolality within the rectum  thereby increasing the
movement of fluid to the rectal contents
Enemas

Viscosity-enhancing agents e.g. glycerol, may be included to aid

retention of the formulation within the rectum and to reduce the
incidence of seepage

Usually anti-inflammatory, purgative or sedative or given to allow

X-ray examination of lower bowel.

E.g magnesium sulphate enema

Retention enemas are administered to give local action of a drug

(e.g prednisolone in Ulcerative colitis) or for systemic absorption
(e.g diazepam or paracetamol)
Patient lies on one side during administration and remains there for
30 minutes to allow distribution of medicament.

Packaged in plastic containers with a nozzle for insertion into

rectum.

Microenemas are single dose, small volume solutions. E.g docusate

sodium for relieving constipation
Containers for enemas

Manufactured enemas will be packed in disposable polythene or

polyvinyl chloride bags sealed to a rectal nozzle.

Extemporaneously prepared enemas are packed in amber glass

bottles.

Special labels and advice for enemas

Patient should be advised on how to use enema and time of onset of

action

“For rectal use only” should be mentioned

Presentations

Instruction on use of
oral syringe
Nasal drops
Ear drops
Nasal Spray

Assignment on “Enemas: Types, Uses and Procedure”