INCOMPATIBILITIES

Incompatibilities
Incompatibles are substances which have
opposite medicinal properties, or
substances when mixed together, react
chemically to produce other substances.
An understanding of incompatibilities can
save the pharmacist valuable time in
compounding as well as ensure the
therapeutic efficiency of the products.
Incompatibilities range from minor to
dangerous.

Incompatibilities
Incompatibilities are divided into three
classes:
Therapeutic incompatibilities
Physical incompatibilities
Chemical incompatibilities

Types of Incompatibilities
1. Therapeutic Incompatibility
They exist when the response to one
or more drug is of different nature or
intensity than that intended by the
prescriber.
When circumstances produce a feeling
of doubt on the part of the pharmacist,
the prescribing physician should be
consulted.

Therapeutic incompatibility
1. Synergistic (or additive) combination
When certain drugs having the same
pharmacologic action are prescribed together,
the combined action they produce is greater than
the sum of their individual actions.
Such combinations should be in reduced amount.
The synergistic action will sometimes be desired
to decrease toxicity or reduce cost of prescription

Therapeutic incompatibility
Synergistic (cont.); examples of useful
synergistic effect
Combinations of sulfonamides show less
nephrotoxicity than a single sulfonamide.
Neomycin erythromycin combination has a
broader spectrum than either antibiotic alone.
Aspirin codeine combination reduces the
amount of expensive codeine required.

Therapeutic incompatibility
2. Antagonistic combinations
When two or more drugs having opposite
pharmacological action are prescribed together,
their actions cancel each other and the resulting
prescription will have no therapeutic action.
Stimulants with sedatives (hypnotics) e.g. caffeine
with chloral hydrate.
Purgatives with antidiarrheals e.g. MgSo4 with tannins
Acidifiers with alkalinizers e.g. aspirin with AL(OH)3.

Therapeutic incompatibility
3. contraindication
Are drugs when prescribed together
may lead to increased toxicity or
decrease activity.
Tetracycline is contraindicated with
any drug containing Ca2+ ions as it
form non-absorbable complex.
Inactivation of sulfa drugs by
procaine HCI.

Therapeutic Incompatibility
4. Dosage Error:
can result from the administration of a single
high dose, or the too frequent administration.
R/
Atropine sulphate
6 mg
Phenobarbital
360 mg
Ft. caps, i mitte xii
sig. caps, i t.d.s

- Dosing errors, unclear prescription

Therapeutic Incompatibility
Dosage errors
Rx
Codeine phosphate
Ammonium chloride
Ft. caps, i mitte xx
sig; caps, ii q.h.

15 mg
500 mg

2. Physical Incompatibilities
Physical incompatibilities are often called pharmaceutical incompatibilities and are evidenced
by the failure of the drugs to combine properly.
These incompatibilities produce a mixture which is
unacceptable in appearance and taste and may
result in non-uniform dosage form.

1.Incomplete solution:
Gums are insoluble in alcohol.
resins are insoluble in water

Physical Incompatibilities
2. Precipitation:
Resins are precipitated from alcoholic solution
when water is added
Camphor and volatile oils are salted out from
their aromatic water when soluble salts are
added
3. Separation of immiscible liquids.
4. Eutexia; formation of eutictic mixture.
5. Incorrect form prescribed,e.g. alkaloidal salt
dissolve in liquid paraffin.
6. Adsorption at solid surface; Adsorption on solid
surfaces; such as adsorption of anti-microbial
agents on rubber closure or plastic container.

3. Chemical Incompatibilities
This type of incompatibility exists when
agents are prescribed that react chemically
when mixed, altering the composition of one
or more of the constituents.
Examples;
- formation of precipitate
- evolution of gas
- colour change

Evolution of gas:
R/

amm. Carbonate
Amm. Chloride
Acetic acid
syrup of cherry
Fait solution
Amm. Carb. + acetic acid

CO2

Manifestations of Incompatibility
Insolubility of prescribed agent in vehicle
(physical)
Immiscibility of two or more liquids (physical)
Precipitation due to change in menstrum that
results in decreased solubility (physical)
Eutexia-the liquefaction of solids mixed in
dry state (physical)
Cementation of insoluble ingredients in liquid
mixtures (physical)

Manifestations of Incompatibility
Change in color (chemical)
Oxidation-reduction or explosive reaction
(chemical)
Precipitation due to chemical reaction
(chemical)
Inactivation of sulfa drugs by procaine HCI
(therapeutic)
Inactivation of tetracycline by calcium ions
(therapeutic)

Corrective Measures

Corrective Measures
Addition of an ingredient that does not alter the
therapeutic value.
Change of an ingredient. Minor changes such as a
soluble form of an ingredient for an insoluble form
are included.
Change of a solvent.
The utilization of special techniques in
compounding, such as treating each ingredient
separately.
Omission of an agent that has no therapeutic value,
or that may be dispensed separately.
Utilization of special techniques in compounding

Intentional incompatibilities

Intentional Therapeutic incompatibilities

Such circumstances rarely occur, but when they do it
does not necessarily indicate a moment of forgetfulness
on the part of the physician. Such agents may have been
used together in order for one agent to modify the
activity of the other.
Examples:
Atropine should antagonize the depressant effect of
morphine to the respiratory tract.
Central nervous system stimulants may be used to
overcome the drowsiness produced by anti-histaminic.
A mild laxative antacid such as Mg(OH)2 may be used to
overcome the constipating effect of an astringent antacid
such as AL(OH)3.

Intentional Chemical Incompatibility

Strong iodine solution U.S.P. (Lugols solution)

R/
Iodine
50 gm
Potassium iodide 100 gm
purified water ad 1000 ml
Iodine dissolves in potassium iodide to form
the water soluble I3 complex.

Intentional chemical incompatibles

Carbonaeous mixture
(Postion Revier Mixture):
Solution A: R/
Sodium bicarbonate
Simple syrup
Water to

Solution B: R/

Citric acid
Syrup lemon
Water to

3.5 gm
30.0 ml
150 ml

4.0 gm
30.0 ml
150 ml

Fait Mist. A and B, Mitte 50 ml of each

one tablespoonful from solution A is mixed with
an equal volume of solution B and the mixture is
taken when effervescence is about to cease

Sig.:

Intentional Physical incompatibilities

Tincture myrh is diluted with water to give
a precipitate which is used as a gargle in
the treatment of tonsillitis.