Physical or
Pharmaceutical Incompatibilities is that 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).
b) Precipitation –
Mucilagenous, albuminous substances and some metallic salts are
precipitated from aqueous solution by addition of alcohol.
E.g. 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 solution frequently show precipitation on
addition of electrolytes.
e) 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 precription.
d) Liquefaction of solid
ingredients – This is due in most cases to the formation of
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.
E.g. 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 menthol forms a damp powder. But
one part salol and 2 parts menthol forms a dry mixture.
Compounds like acetanilid,
antipyrin, betanaphthol, resorcinol, thymol, phenol, etc. may also
liquefy when rubbed together. The liquefaction may also be due to
liberation of water crystallization, or due to the presence of
deliquescent substances.
e) Wrong form of the
ingredients prescribed – Sometimes alkaloidal salts are to be
dissolved in liquid petrolatum, resulting in failure to dissolve, but
by substituting the alkaloid for the alkaloidal salt, complete
solution takes place. (Free alkaloids are soluble in liquid
petrolatum while alkaloidal salts are insoluble).
f) Gelatinization –
Solution of acacia is gelatinized by the addition of ferric salts.
Collodion is also gelatinized by the addition of phenol.
The above physical
incompatibilities may be remedied by any one of the following as the
case may be:
1.Omission of an
unimportant ingredient of little therapeutic value.
2. Dispensing the
ingredients separately.
3. Addition of an inert
ingredient to correct the difficulty.
4. Alteration in the
solvents used (substituting alcohol or glycerin for water or vice
versa).
5. Emulsification or
suspension.
6. Changing the order of
mixing the ingredients.
7. Changing the bulk of
the preparation.
8. Use of a different
form of the same ingredient.
9. Addition of stiffening
agents as in ointments and suppositories.
10. The addition of an
ingredient which promotes solubility.
The above remedies may be
illustrated in the following prescriptions.
Rx (Illustration of
Remedy No. 1)
Tr. of Iodine
….....................2cc
Muc. Of acacia
….................4cc
Alcohol
…...........................10cc
M.S.A
Sig. As directed.
A disagreeable looking
preparation results, due to the precipitation of acacia by the
alcohol. The acacia if left out will produce a nice preparation.
Rx (Illustration of
Remedy No. 2 and 3)
Phenylis Salicylatis
…....................ii oz
Acidi Acitylsalicylic
.......................i oz
Strychniae Sulfatis
…......................1/4 gr
M. ft. cap. No. 24
With the exception of
strychnine sulfate the two other ingredients are sources of trouble.
When mixed together will produce either a wet mass or a liquid. With
the consent of the physician the phenylsalicylate may be dispensed in
a separate capsule and the instruction changed accordingly.
Or if 1 grain of kaolin is
triturated with acetyl salicylic acid then the strychnine sulfate and
phenylsalicylate added in the the order 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
absorbent 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 (Illustration of
Remedy No. 3)
Tr. Cannabis Ind. /
aa …........................i foz
Tr. auranti Aurora/
Tr. Rhei
....................................................i foz
M.
Sig. ½ tsp. At night.
Te 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 of
an equal volume of honey to the 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, guaiac, 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 (Illustration of
Remedy No. 4)
Potassium Bromide /
aa ..................................v oz
Chloral hydrate /
Aromatic Elixir
….............................................iv foz
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 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 over dose 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 corresponding increased. Or the aromatic elixir may be
replaced by an 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 insure uniformity in case
of refill.
Rx (Illustration of
Remedy No. 5)
Olei Morrhuae
…..................................ii foz
Syrupi
...................................................iv foz
Aquae Anisi
..........................................ii foz
M.
Sig. Tsp. t.i.d
There will be two layers
formed, the oil forming the upper layer. The addition of some
emulsifying agent will improve the preparation. The general procedure
for the preparation of emulsion (Continental, English or a
combination of the two) should be followed and provide with a “shake
well” label. To be placed in a wide-mouth bottle preferably
amber-colored.
Rx (Illustration of
Remedy No. 6)
Cod Liver Oil
….................................15cc
Acacia
................................................4 cc
Syr. Of Tolu
…...................................15cc
Dist. Water, qs
...................................60cc
M.
Sig. Tsp. t.i.d.
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 borax is dissolved in the
syrup with a little water and then added to the emulsion, the
formation of tough mass is prevented. The sugar prevents the
gelatinizing effect of the borax of the acacia.
Rx (Illustration
of Remedy No. 7)
Potassium Bromide
…..................v oz
Peppermint water
.........................i foz
M.ft. Sol.
Sig. Tsp. At bedtime.
The oil present in the
peppermint water will be thrown out of solution and will float on the
surface.
This us due to the salting out action of the Potassium bromide. This may be remedied by filtering or by substituting ½ of the peppermint water with distilled water. The bulk may also be doubled by addition of an equal volume of water, and with the permission of the physician the dose is also increased accordingly.
This us due to the salting out action of the Potassium bromide. This may be remedied by filtering or by substituting ½ of the peppermint water with distilled water. The bulk may also be doubled by addition of an equal volume of water, and with the permission of the physician the dose is also increased accordingly.
Rx (Illustration of
Remedy No. 8)
Cocaine Muriate
….....................x gr
Liquid Petrolatum, qs
….............i foz
M.
Sig. Use as directed.
Cocaine muriate is insoluble
in the liquid petrolatum. With the permission of the physician,
cocaine may be substituted and a clear solution will be produced.
In cases where alkaloidal
salts are to be dissolved in liquid petrolatum or mineral oils. The
substitutions of the free alkaloid, prevent the incompatibility,
since the free alkaloid is soluble while alkaloidal salts are not.
Rx (Illustration of
Remedy No. 9)
Phenol
..........................................xx gr
Cacao Butter
................................iii oz
M. ft. supp. #x
Sig. One at bedtime.
Phenol, salol, or chloral
hydrate when mixed with cacao butter produces a lowering in the
melting point of the cacao 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 37oC,
that is the melting point must remain approximately 1oC
below body temperature.
Rx (Illustration of
Remedy No. 10)
Iodi
…..............................v gr
Adipis Lanae
...................i oz
Petrolati, qs ad.
................i oz
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 15 minims of
water can be used to dissolve the iodine; the product then being
taken up by the wool fat and incorporated into petrolatum.
