DRUG INCOMPATIBILITIES b.
Precipitation- Mucilaginous, albuminous substances and some
In the pharmaceutical sense, the term incompatibility refers to
any combination of ingredients, which possesses antagonistic qualities
of a therapeutic, a physical or a chemical nature. The word
incompatibility in a broad sense may mean lack of agreement so that
when the ingredients called for in a prescription do not agree they are
said to be incompatible.
Types of Incompatibility:
1. Physical or Pharmaceutical Incompatibility
2. Chemical Incompatibility
3. Therapeutic Incompatibility
I. PHYSICAL (OR PHARMACEUTICAL) INCOMPATIBILITY
is the form of disagreement depending chiefly on the question of
relative solubility, which is evidenced by the failure of the ingredients
to combine in such a way as to make a satisfactory product. Or simply,
we may define it as that form of disagreement in prescriptions, which
do not involve any chemical reaction.
Evidences of Physical Incompatibility:
a. Incomplete Solution- In this case the pharmacist should guard
against the use of heat. Sometimes the failure to dissolve is due to the
use of wrong solvent. (water instead of alcohol or vice versa).
metallic salts are precipitated from aqueous solution by the addition of
alcohol.
Camphor in camphor water and volatile oils are precipitated
from aromatic waters when metallic salts are dissolved in the liquid.
Boric acid is precipitated from saturated solution when tragacanth is
dissolved in the liquid. Colloidal solutions frequently show
precipitation on addition of electrolytes.
c. Separation of Immiscible Liquids- Oils dissolved in alcohol
usually separate on addition of water. Spirit of ethyl nitrite separates
and floats as a layer when a substantial proportion of potassium citrate
is present in the prescription.
d. Liquefaction of Solid Ingredients- This is due in most cases to
the formation of a eutectic mixture in which the fusing point of the
mixed ingredients is lowered more than that of any single one and also
lower than the room temperature. A good example is the mixture of
salol and menthol.
If 2 parts of salol and 1 part of menthol are mixed it will form a
syrupy liquid, while one part of salol and 1 part of menthol forms a
damp powder. But 1 part salol and 2 parts of menthol forms a dry
mixture.
Compounds like acetanilide, antipyrin, betanaphthol, resorcinol,
thymol, phenol, etc., may also liquefy when rubbed together. The
liquefaction may also be due to liberation of water crystallization, or The above remedies may be illustrated in the following prescriptions:
due to the presence of deliquescent substances.
Rx No.1
e. Wrong form of the Ingredients Prescribed- Sometimes Tincture of Iodine 2ml
alkaloidal salts are to be dissolved in liquid petrolatum, resulting in Mucilage of acacia 4ml
failure to dissolve, but by substituting the alkaloid for the alkaloidal Alcohol q.s 10ml
salt, complete solution takes place. (Free alkaloids are soluble in liquid M.S.A
petrolatum while alkaloidal salts are insoluble). Sig. As directed.

f. Gelatinization- Solution of acacia is gelatinized by the addition A disagreeable looking preparation results, due to the
of ferric salts. Collodion is also gelatinized by the addition of phenol. precipitation of acacia by the alcohol. The acacia if left out will produce
a nice preparation.
The above Physical Incompatibilities may be remedied by anyone of
the following as the case may be: Rx No.2
Phenyl salicylate zii
1. Omission of an unimportant ingredient of little therapeutic Acetylsalicylic acid zi
value. Strychnine sulfate gr. ¼
2. Dispensing the ingredients separately. M.ft. cap. No.24
3. Addition of an inert ingredient to correct the difficulty.
4. Alteration in the solvents used (substituting alcohol or glycerin With the exception of strychnine sulfate the two other
for water or vice versa). ingredients are sources of trouble. When mix together will produce
5. Emulsification or suspension. either a wet mass or a liquid. With the constant of the physician the
6. Changing the order of mixing the ingredients. Applicable to phenyl salicylate maybe dispensed in a separate capsule and the
eutectic substances instruction changed accordingly.
7. Changing the bulk of the preparation.
8. Use of a different form of the same ingredient. Or if 1 grain of Kaolin is triturated with acetylsalicylic acid then
9. Addition of stiffening agents as in ointments and suppositories. the strychnine sulfate and phenyl salicylate added in the order in
10. The addition of an ingredient which promotes solubility. named, the product will be stable for at least two weeks. Gentle
trituration must be used throughout and avoid tight packing of the
contents of the capsules.
Besides Kaolin any other adsorbent powder like starch
glycyrrhiza, or magnesium oxide may be used, but in the case of
magnesium oxide the consent of the physician should be secured
because of its therapeutic value.
Rx No.3
Tincture of Cannabis or
Tincture of Auranti Aurora fzi
Tincture of Rhei fzi
M.
Sig. ½ tsp. at night
The above physical incompatibility is caused by mixing highly
alcoholic resinous tincture of cannabis with tincture of lower alcoholic
strength, resulting in the precipitation of the resinous matter of
Cannabis.
In such case the addition an equal volume of honey to highly
alcoholic liquid before mixing with lower alcoholic or even aqueous
liquid will help in satisfactory suspension of the resin. This may also
be applied, when tr. of asafaetida, quaiac, lupulin, myrrh and similar
substances are to be mixed with aqueous liquid. The separation in bulk
of the resinous matter may also be prevented by addition of other
protective agents like syrup or glycerin.
Rx No.4
Potassium bromide or Chloral hydrate zv
Aromatic Elixir fziv
M.ft. sol.
Sig. One tsp. at bedtime
This physical incompatibility is due to the selective preference
of the potassium bromide on the water present in the elixir and the
chloral to that of the alcohol. When recently compounded the solution
is clear, but later on turbidity develops and ultimately two layers are
formed. The lower layer contains all the potassium bromide and water
with portion of the alcohol while the upper layer contains all the
chloral hydrate and the remainder of the alcohol. The danger is that
the patient may take an overdose of chloral.
This may be remedied by diluting the elixir with an equal
volume of water, thus the prescription may be doubled in bulk by
farther addition of water and the dose is correspondingly increased. Or
the aromatic elixir may be replaced by aromatic water, or by one of the
elixirs of the National Formulary of low alcoholic strength.
Whichever procedure is adopted, the physician should be
notified and proper notations should be made upon the original
prescription to ensure uniformity in case of refill.
Rx No.5 Rx No.7
Oil of Morrhuate fzii Potassium bromide fz
Syrup fziv Peppermint water fzi
Anise water fziii M.ft.sol.
M. Sig. tsp. at bedtime
Sig. tsp. t.i.d
The oil present in the peppermint water will be thrown out of
There will be two layers formed, the oil forming the upper layer. solution and will float on the surface. This is due to the salting out
The addition of some emulsifying agent will improve the preparation. action of the potassium bromide. This may be remedied by filtering or
The general procedure for the preparation of emulsions (continental, by substituting ½ of the peppermint water with distilled water. The
English or a combination of the two) should be followed and provide bulk may also be doubled by addition of an equal volume of water,
with a “shake well” label. To be placed in a wide mouth bottle and with the permission of the physician the dose is also increased
preferably amber colored. accordingly.

Rx No.6 Rx No.8
Cod Liver Oil 15ml Cocaine Muriate gr.X
Acacia 4gm Liquid petrolatum, q.s fzi
Syrup of Tolu 15ml M.
Sodium borate 1gm Sig. Use as directed
Distilled water 60ml
M. Cocaine muriate is insoluble in the liquid petrolatum. With the
Sig. tsp. t.i.d permission of the physician, Cocaine may be substituted and a clear
solution will be produced.
If the oil is emulsified and then the borax previously dissolved
in water is added, there will be formation of a tough solid mass, but if In cases where alkaloidal salts are to be dissolved in liquid
borax is dissolved in the syrup with a little water and then added to petrolatum or mineral oils. The substitution of free alkaloid, prevents
the emulsion, the formation of a tough mass is prevented. The sugar the incompatibility, since the free alkaloid is soluble while alkaloidal
prevents the gelatinizing effect of the borax on the acacia. salts are not.
Rx No.9
Phenol gr.xx
Cocoa Butter ziii
M. ft. sup. #x
Sig. One at bedtime.

Phenol, salol, or chloral hydrate when mixed with cocoa butter

produces a lowering in the melting point of the cocoa butter and the
resulting suppositories would be too soft. In this case, the addition of
some hardening agent, like wax or stearic acid is indicated. Care
should be taken however that the resulting melting point should not
exceed 37°C., that is, the melting point must remain approximately
1°C below body temperature.

Rx No.10
Iodine gr.v
Adipis Lanae zi
Petrolatum Zi
M. ft. Unguentum

It is practically impossible to reduce iodine to a state of

subdivision sufficiently fine to permit its satisfactory incorporation
into an ointment. However, it is easily soluble in a concentrated
solution of potassium iodide, and the resultant solution can then be
taken up in an absorption base. In this case a solution of 10 grains
potassium iodide in 15minims of water can be used to dissolve the
iodine; the product then being taken up by the wool fat and
incorporated into the petrolatum.