INCOMPATIBILITIES – PHARMACEUTICS II (Dispensing Pharmacy) D. Pharm 2nd year PDF Notes


It may be defined as when several ingredients are mixed together, they may
interact with each other so that an undesirable product is formed which alter
or affect the appearance effectiveness & safety of the preparation.



1. Physical incompatibility: When two or more substances are combined together, a physical
change takes place and an unacceptable product is formed.


a. Insolubility: It is due
the substances are insoluble in vehicle.

Method to overcome: Suitable
vehicle may be taken or by adding of suspending agent.


b. Immiscibility: This is
due to immiscible nature of two liquids.

Ex: Oil in water, Chloroform in water

Method to overcome: By
adding suitable emulsifying agent.


c. Precipitation: Resins are
in soluble in water & forms precipitate which is indiffusible.

Method of
This may be corrected by the adding of a suspending agent such as
tragacanth which helps to suspend the precipitation.


d. Lequification: This
is due to the formation of a liquid when two solids such as phenol, thymol,
menthol, camphor etc. are mixed together. It causes instability in the
preparation & in the presence of moisture various micro-organisms can
attack fast.

Method of overcome: To overcome
this powders such as light kaolin or MgCo3 which can absorbed
moisture are mixed to maintain the free flowing property of the preparation.


Chemical Incompatibility: Chemical incompatibility may be a result of
chemical interactions between the ingredients of a prescription and harmful or
dangerous products may formed. It is divided into two groups.

A. Tolerated incompatibility: The
chemical interaction can be minimised by changing the order of mixing or mixing
the solutions in dilute forms but no alteration is made in the formulation.

Ex: Strychnine HCL with Aromatic spirit of ammonia.


HCl Solution

spirit of Ammonia


Type: Chemical Incompatibility

           Alkaloid salts with alkaline


HCl is alkaloidal salt. Aromatic sprit of ammonia is alkaline substances
strychnine HCl is reacts with Aromatic spirit of ammonia & produces free
alkaloid which is insoluble in water.


Label:  Shake will before use.



B. Adjusted incompatibility: This type of incompatibility is prevented by the addition or
substitution of ingredients which does not affect the therapeutic action.

Ex: Sodium salicylate & lemon syrup by mixing these two salicylic
acid is ppt out it is in-diffusible. It is corrected by compound tragacanth


Sodium salicylate

Lemon syrup


Type: Chemical incompatibility-soluble salicylates with acid


Incompatibility: Lemon syrup contains citric acid. It decomposed sodium
salicylates into salicylic acid it is indiffusible.

to Overcome:
Lemon syrup prescribed as flavouring
& sweetening agent. Hence it can be replaced by simple syrup & tincture
lemon. (95% syrup 6% tincture lemon).


Other examples for Chemical

1. Quinine sulphate, sodium salicylate with

Quinine HCl

         Sodium salicylate

         Water (Q.S)

Quinine HCl is an alkaloidal salt. It reacts
with sodium salicylate & quinine salicylate is precipitated out. It is an

to Overcome:
This type of incompatibility can be
prevented by adding suspending agent like compound tragacanth powder. (2 g /100
ml) to the indiffusible substance. It is triturated in the mortor & added
liquid ingredients & then soluble ingredients then dispensed.

Label: Shake will before use

2. Quinine sulphate, KI, H2SO4
& water. Iodides & bromides reacts with quinine SO4, H2SO4
& H2O (Herapathite):

Quinine sulphate

Dil H2So4

Pot Iodide

Water (Q.S)

It is a chemical incompatibility, dilute H2So4
is used to dissolve quinine sulphate when freshly prepared it is clear. But
after 3 days the reaction takes place as follows.

Dil H2So4 reacts
with potassium iodide & liberate hydro iodic acid. This is partly oxidized
by dil H2So4 & free iodide is

Hydro-iodic acid, iodide & quinine
So4 combined together & from a compound known as

it is deposits as olive green scale. It is un-desirable.

to Overcome:
About 3 days use, they may be used
dispensed together. More than 3 days Kl is dispensed in one bottle ingredients
are dispensed in another bottle separately. These ingredients are mixed
together when-ever required.

3. Sodium salicylates with quinine sulphate, H2So4
7 H2O:

Sodium salicylate

Quinine sulphate

Dil H2So4


Type: Chemical incompatibility of soluble salicylate with acid.

Dil H2So4 is prescribed
to dissolve quinine sulphate. But dil H2So4 decomposed
sodium salicylic acid, which is indiffusible.

Overcome: Suspending agents like compound tragacanth powder (2g/100ml) is

Label: shake well before use.


4. Sodium salicylate with caffeine citrate:

Rx:  Sodium salicyalate           -1.0g

Caffeine citrate               -0.5g

Water up to                     -30ml


Type: Chemical incompatibility – Soluble
salicylates with acid

Caffeine citrate is a mixture of equal weights
of caffeine & citric acid. Caffeine is week base & caffeine citrate is
acidic in nature. The citric acid present in caffeine liberates salicylic acid
which gets precipitated, which is indiffusible.

Caffeine citrate is substituted by caffeine
half its quantity. It reduces acidic reaction though caffeine is insoluble
compound. Hence the mixture is clean.


5. Sodium salicylate with ferric salt with

Rx:   Sodium salicylate



Type: This is chemical incompatibility- salicylate with ferric salts.

           In this soluble salicylates reacts
with ferric salts. Sodium salicylate reacts with ferric chloride and produces
ferric salicylate which is precipitated out. It is indiffusible.

to overcome: It is dispensed by using a suspending agent like compound
tragacanth 2%.

“Shake well before use”


6. Sodium salicylate NaHCO3 & Water:


Rx:   Sodium salicylate


         Sodium meta bisulphate

         Peppermint water

Type: Chemical incompatibility – soluble
salicylates with alkali

The solution become dark in colour due to
alkali catalyzed conversion of salicylate to quinoid form.

So anti-oxidant-sodium meta bisulphate is
added to prevent darkening of preparation.


7. Incompatibility of causing evolution of Co2:

Sodium bicarbonate with borax


  Rx:  Sodium bicarbonate

           Borax           Glycerine



Type: Incompatibility of causing evaluation of Co2


When borax is dissolved in water
oxidation reaction takes place & produces boric acid Boric acid reacts with
glycerine & form mono-basic glycerine boric acid. This reacts with NaHCo3
liberating Co2 from the NaHCo3.

Overcome: All the ingredients should be mixed with water in an open vessel
until the effervescence stops. If the reaction is slow hot water is added to
fasten the reaction.


Therapeutic Incompatibility:

When certain
drugs are administered to the patient for a particular therapy but it produce
effects other than that for which it is administered. Here the nature &
intensity of action may be different from what it is expected.

Causes: Adverse reaction, Allergic reaction, Drug
dependence (drug addiction),Drug tolerance, Drug resistance, Idiosyncrasy

Types of incompatibility:


1. Synergism: It
refers to the effects of combined drugs in which the one drug tends to increase
the pharmacological action of other drug or prolong the duration of action of
another drug.

Ex: Phenobarbitone, sodium with Na salicylate

 Phenobarbitone sodium

Sodium salicylate

Peppermint water

In this prescription phenobarbitone
sodium & sodium salicylate minimum per dose. But combined action of these
two ingredients is greater than the sum of their individual action with minimum
dose, the maximum efficacy is obtained.


2. Antagonism: When
two drugs possessing opposite actions, are prescribed in the same prescription
is known as antagonism. So any one of the drug is omitted.


Ex:Phenobarbitone sodium with Ephedrine HCl.


Rx:  Phenobarbitone sodium

Ephedrine HCl

Syrup Chloroform water

Water (U.S)

In this prescription, ephedrine Hcl is
prescribed to prevent bronchial spasm in asthma. It also has the stimulant
action as the cerebrum & respiratory centre. Pheno-barbitone sodium
combined with ephedrine Hcl to overcome. Their stimulation it is an
antagonistic combination.


3. Contraindication: The use of certain drugs which may be contra indicated in a
Particular disease or a Particular patient who is allergic to it.

Barbiturates & Morphine in Asthma.

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