INCOMPATIBILITIES IN PRESCRIPTION

Definition of Incompatibility:
Incompatibility
occurs as a result of mixing of two or more
Antagonistic Substances & an undesirable
product is formed which may affect the safety,
efficacy & appearance of the pharmaceutical
preparation.

Types of Incompatibility:
Physicochemical Incompatibility
A) Physical incompatibility
B) Chemical incompatibility
C)Therapeutic incompatibility

B] CHEMICAL INCOMPATIBILITY
DEFINITION:
It may be as a result of chemical
interactions between the ingredients of a
prescription & a toxic or inactive product may be
formed.
It is due to oxidation-reduction, acid base
hydrolysis or combination reactions.
These reactions may be noticed by effervescence,
decomposition, colour change .

THERAPEUTIC INCOMPATIBILITY

It is result of prescribing
certain drugs to a patient
with
the
intention
to
produce a specific degree of
pcological
action,
but
nature or intensity of the
action produced is different
from that intended by the

Physicochemical Incompatibilty
If mixing two or more drugs or a drug
& excipients, by particular method,
results in a physicochemical change
in the properties of drug or dosage
form, or production of a new chemical
substance
having
different
pharmacological action, it is called as
physicochemical incompatibility.
If incompatibility is prevented by
addition, substitution or elimination of
one or more ingredient is called as

General Methods used

remove incompatibilities.

to

1.Modify the order of mixing

2.Dispense with labels like Shake well
before use
3.Recommend storage condition.
4.Add physical stabilizer. (Suspending or
emulsifying agent)
5.Add
chemical
stabilizer.
(Antioxidant/Buffer)
6.Add preservative.
7.Select soluble , compatible or stable

A] PHYSICAL INCOMPATIBILITY
When two or more than two substances
combined together a physical change takes place &
unacceptable product is formed.
Physical changes involves such as Immiscibility,
Insolubility, Precipitation formation or liquefaction
of solid materials.
The physical incompatibilities may be corrected
by using any one or more of the following methods:
i) Change the order of mixing of ingredients of the
prescription.
ii) Emulsification
iii) Addition of suspending agent
iv) Change in the form of ingredients

Example of Physical Incompatibility &

Their Methods of Correction:
1.Immiscibility:

Oils & Water are immiscible

with each other. They can be made miscible with
water by emulsification.

Example:
Rx
Castor oil
water

upto

15ml
60ml

Make an emulsion.
To overcome this incompatibility an emulsifying
agent is used to make a good emulsion.

2. Insolubility:
It means the inability of material to dissolve in a
particular solvent system.
The liquid preparations containing Indiffusible
solids such as chalk, aromatic chalk powder, acetyl
salicylic acid, phenacetin, zinc oxide & calamine
etc.
Suspending agent
- Increase the thickness of the
preparation.
-Uniform distribution of the insoluble
substances which
facilitating uniform measurement of
each dose.

Example:
Rx
Phenacetin
Caffeine
Orange syrup
Water
upto

3g
1g
12ml
90ml

Make a mixture.
In this prescription phenacetin is an indiffusible
sub.
Compound powder of tragacanth or mucilage of
tragacanth is used as a suspending agent to make
a stable suspension.

3. Settling Suspending
agent
The drug in mixtures containing insoluble
solids(Suspension), during storage settles at the
bottom.

Insoluble solids are of two

types.
Diffusible Solids Kaolin & light
magnesium carbonate remains
evenly distributed.

4.
Poor
Wettability
Levigating agent
Some drugs are poorly wetted
with given vehicle hence these
may float or sink at the bottom of
vehicle. Hence levigation of these
solids with wetting agent such as
glycerine, propylene glycol, or
hydrophilic surfactant helps in the
uniform
distribution
of

5. Precipitation:
A drug in solution may be precipitated , if
the solvent in which it is insoluble is added
to the solution e.g. resins are insoluble in
water.
Volatile oils are soluble in alcohol. When
water is added into the alcoholic solution of
volatile oil, the non aromatic portion of the
oil get precipitated & turbidity appears.
Cap locking Co-solvents
Liquid preparations especially those
containing syrups may show crystallization

6. Grainy Semisolids Non

uniform cooling
Partial solidification of higher
melting point waxes may occur
when cool spatula is used for mixing
or when a hot product is poured in a
cool container.
Grains are also developed during
preparation of creams, if the
aqueous phase & oil phase do not
have same temperatures at the
time of mixing. This can be

7. Liquefaction:
Eutectic mixture
If low melting point solids are mixed together, a
liquid or soft mass known as Eutectic mixture is
produced.
This occurs due to the lowering of the melting
point of mixture to below the room temp. &
liberation of water of hydration.
e.g camphor, menthol, thymol.

Liquefication can be
corrected by
i) Dispensing
individual
ingredient
separately
ii)Compounding powder using diluents
such as lactose, magnesium oxide
or
magnesium
hydroxide
are
separately
mixed
with
eutectic
substances and such mixtures are
mixed to produce final product.
This prevents physical contact of