Solution Classification Depending on

saturation

a. Saturated solution
b. Unsaturated solution
c. Supersaturated solution

Saturated solution
Solution containing maximum amount of solvent at a
particular temperature and pressure and the
homogeneity is destroyed by further addition of solute
is called saturated solution.
Unsaturated solution
The solution that contain less amount of solute than in
the saturated solution at the same temperature and
pressure and further addition of solute is possible is
called unsaturated solution.

Supersaturated solution
The solution that contain more amount of solute than
saturated solution due to special reasons at a particular
temperature and pressure is called supersaturated
solution.
Depending on the method of preparation
a. Simple solution
b. Compound solution

Simple solution
The solution which is formed by dissolving of only one
active ingredient in the solvent is called simple
solution.
Compound solution
When more than one ingredient are dissolved in the
solvent, the preparation is called compound solution.
Depending on the solvent used

a. Aqueous solution
b. Nonaqueous

Aqueous solution
The solution in where water is used as a solvent are
referred to as aqueous solution

Nonaquous solution
The solution having vehicle other than water is called
nonaquous solution.
Formulation of solution

The following factors must be considered during the

formulation of an acidic or basic drugs

1. The solubility of ionized and non-ionized forms of the

drugs
2. The chemical stability of the drugs.
3. The therapeutic efficacy of the drug

Additives
Additives are substances ( other than the active
ingredients) which are included during the formulation
of a dosage form but do not have any therapeutic
activity of their own.
Additives mainly serve as an aid to drug formulation
A number of additives are employed during the formulation
of a solution. These include
• Vehicles
• Suspending agents
• Emulsifying agents
• Viscosity enhancing agents
• Preservatives
• Antioxidants
• Sweetening agents
• Flavouring agents
• Colouring agents etc.
 Vehicles
Vehicles are substances which serve as medium in
which other ingredients of a formulation are dissolved or
dispersed. The most commonly used vehicles in liquid
formulation include
• Water
• Aromatic water
• Syrups
• Glycerol
• Polyethylene glycol
• Propylene glycol
• Ethanol
• Isopropyl alcohol
• Oils (mineral and vegetative oils)
 Water
Water is the most common vehicle used in
pharmaceutical preparations. This is for the following
reasons
– Nontoxic
– It does not interfere with the normal metabolic activity
of the body.
– A wide range of materials dissolve in water
– Available
– Tasteless, colourless and odourless.
– Nonirritant
– It has no pharmacological effect
– Its purity is constant
– Easy to store
Potable water
Potable water is water mainly derived from surface
sources such as lakes, rivers and streams or
underground sources such as spring or well.
its chemical composition depends upon the source from
which it is drawn.
The mineral impurities that it contains should not react
with the medicaments or other ingredients.

Purified water
Purified water is water prepared from suitable potable
water by distillation, ion-exchange treatment, reverse
osmosis or by any other suitable method.
Water for injection
Water for injection is pyrogen-free distilled water
intended for use in the preparation of parenteral
administration.
It is usually prepared by distilling potable water, purified
water or distilled water in special distillation still having
provision for entrapment of water droplets during
distillation.

Sterile water for injection

Sterile water for injection is water for injection that has
been sterilized and packed in suitable containers to
ensure that it remains apyrogenic.
Glycerol
• Glycerol is a viscous polyhydric alcohol.
• It is mainly used as a vehicle for some external
preparations such as ear drops
• It is also act as a cosolvent with water in solutions for
internal use.
• It also act as a sweetening agent and in concentration
above 20% it acts as a preservatives.

Propylene glycol
• Propylene glycol is also used as a solvent for external
preparations and as a cosolvent with water for internal
preparations.
• At a concentration above 30%, it inhibits mould growth
and fermentation.
Polyethylene glycol
• Low molecular weight polyethylene glycols such as PEG
200, 300, 400 etc. are liquid at room temperature.
• They also employed as solvents and cosolvents in
different liquid preparation.
• They are miscible with water.

Ethanol
• Ethanol is very useful solvent for both internal and
external solutions.
• It is miscible with water in all proportions.
• It is also miscible with other solvents or vehicles of liquid
preparations.
• Alcohol has antimicrobial properties.
• It also prevents hydrolysis of certain drugs.

Isopropyl alcohol
• Isopropyl alcohol has solvent properties similar to
ethanol.
• It has a typical odour which is difficult to mask.
Suspending agent
Suspending agent that can be used in liquid preparations
include
• Carbomer
• Sodium carboxy methyl cellulose
• Microcrytalline cellulose
• Methyl cellulose
• Povidone
• Sodium alginate
• Tragacanth
• Xanthan gum
Emulsifying agent
Emulsifying agent used in the formulations of solution
include
• Acacia
• Polysorbates
• Glycerol esters
• Sorbitan esters

Antioxidants
Antioxidants are substance that are added to
pharmaceutical preparations to prevent oxidative
degradation of liable substances in the preparation.
An ideal antioxidant should have the following criteria
• Nontoxic
• Nonirritant
• They should be effective at low concentration under the
expected conditions of storage and use
• They should be soluble in the vehicle
• They should be stable.
• Antioxidant for use in oral preparations should also be
odourless and tasteless.
• Commonly used antioxidants for liquid include
• Ascorbic acid
• Sodium sulphite
• Sodium metabisulphite
• Tocopherol
• Propyl gallate
• Butylated hydroxytoluene and
• Butylated hydroxylanisole
Sweetening agents
Sweetening agents are substances added to formulation
to mask the objectionable taste of the active ingredient
and make the preparation more palatable.
Commonly used sweetening agents for liquid include
• Glucose
• Sucrose
• Honey
• Sorbitol
• Mannitol
• Xylitol
Artificial sweeteners include
• Sodium and calcium salts of saccharine- they are very
soluble in water to form stable solutions over a wide pH
ranges.
• Aspartame- it has been increasingly used as a
sweetening agent in recent years especially for
sweetening foods and drinks. But it hydrolyses in
solution especially when heated at high temperature.
Flavouring agents
Flavouring agents are used to mask unpleasant taste
and odour of active substances and to make medicines
more acceptable to patients, especially children.
• Sweet fruit-flavour- children usually prefer this type of
flavour
• Chocolate
• Anise
• Menthol
• Cinnamon
• Butterscotch
Colouring agents
Colouring agents are generally added to liquid
preparations to mask an unpleasant appearance or to
increase the acceptability of the preparation to the
patients.
Acceptability may be enhanced by inclusion of a colour
that is closely associated with the flavour of the
preparation.
 Colourants to be used should be nontoxic, non-
irritant and compatible with active ingredients
and other ingredients of the preparation.
There are three categories of colouring agents
• Mineral pigments- iron oxides
• Natural colourants and – anthocyanins,
carotenoids, chlorophyll, xanthophylls,
riboflavine, saffron, cochineal and caramel.
• Synthetic organic dyes.-Erythrosine, carmoisine,
brilliant blue, sunset yellow quinoline yellow,
tartrazine etc.
Buffers
Buffers are the mixture of weak acids and its salt or weak
base and its salt.
When this mixture is dissolved in a solvent, it will enable to
resist any change of pH upon the addition of small
quantities of acid or alkali.

Necessity
• To increase the stability
• To increase the solubility of the drug.
• To minimize pain, irritation and necrosis on injection.
• To provide unsuitable preparation for micro-organism
• To enhance the biological activity of the drug.
Pharmaceutical used buffer
• Boric acid buffer :pH 8-10
• Acetic acid buffer :pH 4-6
• Benzoic acid buffer :pH 3-5
• Phosphoric acid buffer : pH 1-3
 Isotonocity Modifiers

When two solutions are separated by a semi

permeable membrane, if there is no
diffusion of solvents through the
membrane i.e. their osmotic pressure are
same then the solutions are called
isotonic.
Eg 0.9% NaCl is isotonic to blood.
Solubility
According to the U.S. Pharmacopeia and National
Formulary, the solubility of drugs may be defined as the
number of milliliters of solvent in which 1 gm of solute
will dissolve at a particular temperature.

For example the solubility of boric acid in water and alcohol

is 18 because 1 gm of boric dissolves in 18 ml
water/alcohol.

It is 4 in glycerine because 1 gm of boric acid dissolves in 4

ml glycerine.
Factors influence the aqueous solubility
1. Temperature
Solubility is highly dependent on temperature. There is
no unique rule. Generally solubility of many drugs
increases with increasing temperature.
e.g. NaCl, KCl

There is also some solute which solubility decreases with

increasing the temperature
e.g. methyl cellulose and calcium salts are more soluble
in cold water than hot water. When solution of methyl
cellulose is heated it tends to be precipitated.
2. pH
Drugs are organic substances which are weakly
acidic or weakly basic and their aqueous
solubility is dependent on the pH of the solvent.

These weak organic acids or weak organic bases

dissociate slightly and their molecular or
undissociated forms are slightly soluble in water.
But at some ranges of pH, they exist
predominantly in ionic or dissociated forms
which are very soluble in water. So by
maintaining optimum pH of the solvent, the
solubility of drugs can be increased.
Weak acid:
The solubility of weak acids is increased by
increasing the pH. pH can be increased by the
addition of base. This is due to the formation of a
water soluble salt.
e.g. Phenobarbital
sulfonamide
The solubility of Phenobarbital at temperature
250C
• pH 2 –insoluble in water
• pH 5.5 poorly soluble 1.25g/1000ml
• pH 9.3 soluble 1000gm/1000ml
 Weak base:
The solubility of weak bases is increased by decreasing
the pH of the aqueous medium. To decrease the pH of
the medium adds an acid which converts the weak base
into salts.
e.g. Alkaloids
Anesthetics
The solubility of atropine
• pH 12 –insoluble in water
• pH 5.5 poorly soluble 2.2g/1000ml
• pH 5.4 soluble 2250gm/1000ml
3. Co-solvency
The process of increasing the solubility of poor water
soluble electrolytes and nonpolar molecules by the
addition of a water miscible solvent in which the
compound is also soluble is referred to as cosolvency.
The solvent used in combination with water to increase
the solubility of the drug are known as co-solvents.
The solubility of a drug in mixed solvents is greater than the
solubility of each individual solvent.

For example a mixture of propylene glycol and water is

used to improve the solubility of Co-trimoxazole.
Manufacturing steps of solution preparation

Solution are manufactured by the direct mixing of the drugs

with solvent. There is no hard and fast rule for mixing.

• The solute is simply added to the solvent in a mixing

vessel and stirring is continued until dissolution is
completed.
• If the solute is more soluble at elevated temperatures it
may be advantageous to apply heat to the vessel
particularly if dissolution rate is slow.
• Size reduction of solid materials help to increase the
total surface area as well as the speed up the process
of solution.
• Solute present in low concentration especially dyes are
often pre-dissolved in small volume of the solvent and
then added to the bulk.
• Volatile materials such as flavours or perfumes are
added at the end of process and often after cooling if
necessary to reduce loss of evaporation.
• To ensure clarity of final solution filtration is done.
• After ensuring the clarity the final product is stored in
suitable container.