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EDSEL A. RUDDMAN.

INCOMPATIBILITIES IN PRESCRIPTIONS FOR STUDENTS IN PHARMACY AND MEDICINE AND ... online

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U. S. D., 662, to the formation of a new compoimd. Rubbing
the balsam with lard for a few minutes the mass gets granular
and then the resinous matter seems to stick together and the lard
is worked out



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INCOMPATIBILITIES IN PRESCRIPTIONS. 177

66.

This gives a clear solution at first but after a day or two
a precipitate is formed. The precipitate gives a test for both
arsenic and iodine. There may 'be an oxy-iodide of arsenic
formed. If this mixture is dispensed at all it should be with
a " Shake well " label. Adding two drams of water does not
entirely prevent precipitation.

66.

The euphorin, aristol, tannic acid, and alum can be
triturated together, producing a powder. On adding the
crystallized carbolic acid to this mixture, it becomes very
soft, almost liquid. This change is the result of bringing
carbolic acid in contact with the euphorin, these two sub-
stances liquefying when triturated together. The mass with
the oil of theobroma makes a mixture too soft to be made
into suppositories. Carbolic add alone has a softening effect on
the oil. In summer it is necessary to render it firmer by the
addition of wax, spermaceti, or some absorbing powder^ as starch
or slippery elm or by standing.

67.

Although the sulphuric acid aids the solution of the
quinine sulphate, it precipitates the glycyrrhizin of the fluid-
extract. The glycyrrhizin, thus precipitated as glycyrrhizic
acid, loses much of its sweet taste and no longer disguises
the taste of the quinine. It would have been better if the
prescriber had omitted the sulphuric acid and directed a shake
mixture. The water causes the separation of a small amount
of inert matter from the fluidextract.



Several chemical reactions take place, depending upon the
manner of filling this prescription: i. Between the hydro-
chloric acid in the tincture and the potassium chlorate, liberat-
ing chlorine. 2. The chlorine thus formed may act upon



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178 INCOMPATIBILITIES IN PRESCRIPTIONS.

the glycerin or alcohol. 3. Between the hydrochloric acid
and the ammonia and glycyrrhizin in the fluidextract, pre-
cipitating the glycyrrhizic acid. 4. Between the iron and
tannic acid in the fluidextract, giving the *black tannate of
iron.



The dose of the arsenic and of the strychnine is between
^/j and ^/g of a grain in this prescription. The maximum
dose of each, as generally given, is not over */io of a grain.
The prescriber should be consulted. Moreover, each pill
would contain about seven grains of medicinal matter, which,
considering the bulky quinine sulphate and extract of gentian,
makes a very large pill. Where such a large pill is prescribed,
twice as many pills are sometimes made as directed and then
the number to be taken at one time is doubled.

JO.

Water can be added to carbolic acid, forming a clear solution.
On adding more water the acid separates as an oily liquid, going to
the bottom. When water has been added so that the pro-
portion is about I part of acid to 15 parts of water, a clear
solution again results. In this prescription there will be a
layer of liquefied acid in the bottom of the bottle. If the
brush should remain in the bottle between the periods of
using it, there is danger that it will beconue saturated with the
strong acid and that the patient will apply it in this condi-
tion. By the use of two drams of glycerin in place of part of
the water a clear solution can be made, and this is what the
dispenser should use.

Tl.

Filled as written this prescription makes a thick mixture that
will run, and on standing a liquid separates. The amount of
starch should be cut down to one third or one fourth of the amount



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INCOMPATIBILITIES IN PRESCRIPTIONS. 1 79

and then boiled with the lime water. By so doing a much
smoother ointment is made and there is practically no separation
of liquid.

78.

EHflFerent results may be obtained by changing the order
of mixing these ingredients. If the corrosive sublimate is
dissolved in the water and then added to the lime water the
yellow mercuric oxide is precipitated. This if mixed with
the mucilage and allowed to stand for some time changes to
a dirty-brown color. If the lime water is added to the solu-
tion of mercury the red-brown basic chloride of mercury is
precipitated. If the solution of mercuric chloride is added
to the mucilage of acacia and then the lime water added to
this no precipitation of mercury takes place. On allowing
this to stand for a few days a flocculent precipitate is formed,
slowly increasing. Acacia prevents the precipitation of a
number of the heavy metals by the alkaline hydroxides.

78.

The bismuth subnitrate is insoluble in the syrup, but a
chemical reaction takes place between it and the hydriodic
acid, as is evidenced by the change in color. Bismuth sub-
nitrate is white; on mixing it with the syrup the color be-
comes yellow and quickly turns to a grayish black. According
to Watts' Dictionary, the oxjriodide of bismuth is copper-colored
and the bismuth iodide is a brilliant gray.

74.

Sodium bromide on being exposed to the air attracts moist*
ure. Pepsin is somewhat hygroscopic if contaminated with
peptones. Pepsin is rendered inert by alkalies, as sodium
bicarbonate.



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l8o INCOMPATIBILITIES IN PRESCRIPTIONS.



75.

The sodium phosphate of the U. S. P. is the NajHP04
and is slightly alkaline to litmus. This alkalinity may cause
precipitation of the strychnine, and it should be neutralized
with a little phosphoric acid before the solutions of sodium
phosphate and strychnine sulphate are mixed.

76.

If the turpentine is poured upon the iodine violent
chemical reaction results, with the formation of violet fumes
of vaporized iodine, caused by the heat generated. While
there is not enough of alcohol to dissolve all of the iodine, it
is best to dissolve as much as possible before adding the
turpentine, which should be added in small portions, cooling
the mixture if necessary. Upon standing the liquid separates
into two layers, the lower one, being much smaller in amount,
is the alcohol. Turpentine and alcohol are not miscible in all
proportions.

77.

According to the National Formulary, Hall's solution of
strychnine contains ^/g of a g^in of strychnine ac.etate to the
dram, together with some acetic acid. Fowler's solution
contains, besides the potassium arsenite, some potassium bi-
carbonate or carbonate (formed by the boiling of the bicar-
bonate in water). This carbonate will react with the acetic
acid, liberating a little carbon dioxide and forming potassium
acetate. If there is an excess of the alkaline carbonate the
strychnine will be liberated as the free alkaloid. The
strychnine will not be precipitated, however, as it is soluble
in no parts of alcohol, and the prescription can be filled
without difficulty.



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INCOMPATIBILITIES IN PRESCRIPTIONS. i8i

78.

The resinous matter in the tincture of myrrh is precipi-
tated by the syrup. By adding the tincture to the syrup in
small portions and shaking well after each addition the resin
comes down in a form in which it can be more readily sus-
pended in the liquid. Tannic acid combines with the mor-
phine to form a compound insoluble in water. On standing
the precipitated matter forms into masses, rendering an even
dosage difficult. Using one or two drams of honey in place of
that much syrup helps to keep the precipitated matter finely
divided.

'*•

In filling this prescription each of the salts was dissolved
in separate portions of water. The potassium iodide solution
was added to the mercuric chloride solution, and at first there
was a red precipitate of mercuric iodide, which was dissolved
by the further addition of the potassium iodide, forming the
soluble potassium mercuric iodide. On the addition of the
ammonium carbonate solution to this no change of any kind
was noticed. However, when the ammonium carbonate solu-
tion was added to the mercuric chloride solution a white pre-
cipitate of ammoniated mercury was formed. On adding the
potassium iodide solution to this mixture the precipitate dis-
appeared and a clear nearly colorless solution was formed.
Probably the ammoniated mercury was decomposed and the
soluble double compound of potassium mercuric iodide was
formed.

80.

When the ingredients of this prescription are mixed the
liberation of iodine commences at once and continues for
some time. The wine and spirit were mixed and neutralized
with ammonia, thinking thereby to prevent the formation of



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l82 INCOMPATIBILITIES IN PRESCRIPTIONS.

iodine, but with practically no benefit. The hypophosphorous
acid in the syrup is not sufficient to prevent the liberation of
iodine^ Filled as written the iodine is precipitated in time, and
also a brown flocculent precipitate is formed. The prescription
should not be dispensed.

81.

This mixture in a short time becomes yellow and within
twenty-four hours it changes to a light brown. The colora-
tion is due largely to the action of the nitrous acid on the
morphine. Less change takes place if the mixture is neutral.
The morphine is converted into nitroso-morphine, pseudo-
morphine, and another base (M. & M., iii. 436).



Although this ointment is brown at first it becomes blue
and then greenish black, due to the ichthyol and iodine.

U.

The pharmacist who received this prescription in attempt-
ing to fill it rubbed the three ingredients together dry and
caused an explosion, whereby he was quite severely injured.
The explosion was due to the reaction between the chlorate
and hypophosphite. The pills can be made by powdering
the ingredients separately, then mixing lightly with powdered
extract of liquorice and massing with water.

84.

Iodine is soluble in about 10 parts of alcohol. As much
of the iodine as possible was dissolved in the alcohol and
then the camphor dissolved in this. This solution was then
gradually added to the mercurial ointment with constant



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INCOMPATIBIUTIES IN PRESCRIPTIONS. 183

trituration and the water was added last. On standing a few
minutes a red precipitate was formed and the mixture sep-
arated into three layers. In the bottom was this red pre-
cipitate, probably mercuric iodide, then a layer of fatty matter,
and on top a hydro-alcoholic fluid containing free iodine.
This mixture was such that it could be shaken up and applied.
On the third day the red precipitate had disappeared, leav-
ing the yellow fatty matter and a fluid somewhat red and
containing a little free iodine. Seven days later the liquid
was yellowish brown and contained only a trace of iodine.
Part of the iodine probably combined with the mercury to
form mercuric iodide, and part was probably reduced to a
soluble iodide, which dissolved the mercuric iodide. Another
part of the iodine probably combined with some of the cam-
phor and fatty matter. Although the activity of the iodine
is very much diminished the mixture is decidedly active on
account of the mercuric salt formed.



89.

Creolin is said to be an emulsion of cresol, obtained by means
of resin soap. It forms a mOky emulsion or mixture with water.
This prescription may be filled by dissolving the acid in
the water and adding the creolin slowly with constant shak-
ing. Part of the creolin separates on standing, but it may
be readily mixed by agitation. As this is an eye-lotion and
not clear, an attempt was made to filter it, but with the result
of separating nearly all of the creolin. It should be dispensed
with a " Shake well " label.



86.

The citric acid should be dissolved in the boiling water
and then the magnesium carbonate added to this. Carbon
dioxide is liberated and magnesium citrate goes into solution.
The addition of borax does not cause any precipitation, al-



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i84 INCOMPATIBILITIES IN PRESCRIPTIONS.

though the solution is alkaline. If the borax is added to
the solution of citric acid and then the magnesium carbonate
a large amount of the last ingredient is not dissolved, the
acid having been nearly neutralized by the borax.



87.



Gold and sodium chloride precipitates the sulphates of
atropine and strychnine and the alkaloids in cinchona. There
is about thirty per cent, of alcohol present but not enough to
prevent precipitation. By dissolving the gold and sodium
chloride in water and adding an equal weight of sodium thio-
sulphate a compound is formed that does not precipitate the
alkaloids from this mixture. The gold may be reduced on
standing for some time. Water precipitates inert matter from
the fiuidextract. Atropine and strychnine are somewhat an-
tagonistic in their physiological action.



88.



In medium-sized medicinal doses morphine and atropine
are physiologically incompatible. But the minute dose of
atropine in this prescription assists rather than diminishes the
action of morphine by relieving the cardiac depression, indi-
gestion, and constipation.



The pharmacist should not use the excipient directed.
Potassium permanganate is easily reduced by organic matter,
which it in turn oxidizes. Some excipient must be chosen
that will not reduce the permanganate. A mixture of equal
parts of petrolatum, paraffin> and kaolin makes a good one, or
wool-fat with kaolin may be used. When filled as written no
permanganate could be detected at the end of a week.



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INCOMPATIBIUTIES IN PRESCRIPTIONS. 185

90.

The oil of turpentine reacts with the acids, with the gen-
eration of much heat, and unless care be taken it will be
ignited. The acids should be mixed and cooled and then
added in small portions to the oil, cooling after each addi-
tion. The alcohol should be added last, after the mixture is
cold, so as to avoid volatilization.

91.



On mixing the acid with the bicarbonate in the presence
of water effervescence takes place, due to the liberation of
carbon dioxide; a nearly colorless quite strongly alkaline so-
lution results. If this is allowed to stand undisturt)ed for
two or three days the lower part of the liquid will be of a
light-brown color and the upper part of a dark brown, and
finally it will become dark brown throughout. An aqueous
solution of a salicylate turns dark when exposed to the air,
probably on account of the formation of some oxidation
products. This change takes place much more quickly when
the solution is alkaline. If the physician had prescribed
sodium salicylate instead of the salicylic acid and sodium
bicarbonate he would have gotten practically the same phys-
iological effect (unless he wanted the effect of the alkali too),
made a better preparation pharmaceutically, and saved the
pharmacbt considerable time and work. The patient should be
informed of the change of color that will take place.



n.

This can be filled by dissolving the allcaloidal salts in the
syrup of lemon and tincture of iron, adding the water, and
then the phosphoric acid last. The solution is clear and of a
pale reddish color previous to the addition of the acid. After
the addition of the acid the solution becomes colorless and



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l86 INCOMPATIBILITIES IN PRESCRIPTIONS.

slightly turbid and in a few minutes a heavy precipitate is
formed. The three disturbing causes are tincture of iron,
phosphoric acid, and quinine sulphate, leaving out any one
of which prevents precipitation. If the amount of quinine is
reduced to three grams there is but little precipitation and
none if it is reduced to two grams. The decoloration is due
to the formation of ferric phosphate, which is insoluble in
water but soluble when there is an excess of free acid. By using
enough of dilute sulphuric acid to dissolve the quinine in water
no precipitation results.



93,



When this prescription is fiUed as written a crystalline pre-
cipitate forms at once. Both Fowler's solution and potassiimi
iodide precipitate the strychnine. Neutralizing Fowler's solution
will prevent its causing trouble, but there will still be danger from
the potassium iodide precipitating the strychnine.



94.



The first two ingredients when mixed give a greenish-
brown solution, which when diluted with water gives a
deep-blue color and largely diluted gives a violet color.
On adding the sulphurous acid the color is destroyed within
a few minutes. The ferric chloride is reduced to the ferrous
chloride and sulphate, and a ferrous salt does not give a
coloration with carbolic acid. If the sulphurous acid is added
direct to the tincture of ferric chloride a deep-red solution of
ferric sulphite is formed, which changes to ferrous sulphate
and becomes colorless. Adding the carbolic acid to this gives
no coloration. It makes little or no difference what order is
observed in filling this prescription.



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INCOMPATIBILITIES IN PRESCRIPTIONS, 187

9S.

Ferrous sulphate usually contains some ferric sulphate and
this reacts with the calcium hypophosphite to form ferric
hypophosphite and calcium sulphate, the former being only
sparingly soluble, and the latter requiring 380 parts of water
for solution. Part of the sulphuric acid of the Epsom salt
will go to form calcium sulphate. In an acid solution the
potassium chlorate would have an oxidizing effect on the
ferrous sulphate and also on the hypophosphite; in this pre-
scription it probably has but little chemical action. The
solution of strychnine is a British preparation containing
about one per cent, of strychnine hydrochloride. Potassium
chlorate and a hypophosphite should not be triturated to-
gether dry, as they form an explosive mixture.

96.

This mixture makes a clear alkaline solution, colorless at
first, but in a few minutes acquiring a light-brown color,
which slowly becomes dark red brown or almost black. This
coloration is due partly to the alkaline salicylate acquiring a
red color in the air, and partly to the effect of action of the
spirit of nitrous ether upon the salicylate. Prof. Attfield
suggests the formation of nitrosalicylic acid which is colored.
The change does not take place quite as rapidly when the
spirit is mixed with the carbonate previous to the dissolving
of the sodium salt. Generally the spirit of nitrous ether is
acid, and when ammonium carbonate is added to it carbon
dioxide is given off.

97.

This was filled in several ways, the result being the same.
The codeine was triturated with a little water and a half dram
of dilute phosphoric acid added to dissolve the alkaloid. The
hydrocyanic acid was next added, and then the tincture of
iodine, which did not precipitate the alkaloid, but was itself



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i88 INCOMPATIBILITIES IN PRESCRIPTIONS.

decolorized at once. The further addition of the water sim-
ply diluted the solution.

If the tincture of iodine is added to the sc^ution of codeine
in water and phosphoric acid a reddish-brown precipitate is
formed, consisting of codeine and iodine. This precipitate
is not dissolved by adding an excess of phosphoric acid or
sulphuric acid, but the twenty minims of dilute hydrocyanic
acid dissolves the precipitate and makes a clear colorless solu-
tion. The explanation is that the hydrocyanic acid reduces
the iodine to an iodide and thus breaks up the compound
of codeine and iodine. Other reducing agents, as sodium
hyposulphite, have a similar effect.

98.

Reaction takes place between the calcium hydroxide and
the mercurous chloride, forming calcium chloride and the
black mercurous oxide. This is similar to the " black wash '*
of the National Formulary.

99.

The best way to fill this prescription is to dissolve the
corrosive sublimate in the glycerin mixed with a half dram
of water. Then to this solution add all at once the syrup of
lime. A yellow precipitate is formed at first, but this quickly
disappears and a clear slightly yellowish liquid results. A
slight light-gray precipitate is formed after standing a
day, and this increases slowly for several days. Certain or-
ganic substances, such as glycerin, sugar, and gum arable,
have the power of preventing the precipitation of solutions of
some of the metallic salts by alkali hydroxides.

If the syrup of lime is added slowly to the solution of
corrosive sublimate a yellow precipitate is formed, but is re-
dissolved again when the water is added. Quite a heavy steel-
gray precipitate forms within an hour and it slowly increases
on further standing. A similar result takes place if the solu-
tion of mercuric chloride is added to the syrup of lime.



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JNCOMPATIBIUTIES IN PRESCRIPTIONS. 189

100.

Free bromine is formed if the potassium twomide is added
to the tincture and the free bromine combines with antipyrine.
If the bromide is dissolved in water and then added to the
tincture of iron previously diluted with water no bromine is
liberated. Antipyrine gives an intense red coloration with the
tincture of iron.

101.

The compound tincture of iodine was official in the 1870
Pharmacopoeia and contained iodine and potassium iodide
dissolved in alcohol. Reaction takes place between the gold
chloride and the potassium iodide. " Potassium iodide, added
in small portions to a solution of auric chloride (so that
the latter is constantly in excess where the two salts are in
contact), and when equivalent proportions have been reached,
gives a yellow precipitate of aurous iodide, Aul, insoluble
in water, soluble in large excess of the reagent; the precipi-
tate is accompanied with separation of free iodine, brown,
which is quickly soluble in small excess of the reagent as a
colored solution. But on gradually adding auric chloride to
solution of potassic iodide, so that the latter is in excess at
the point of chemical change, there is first a dark-green solu-
tion of potassio-auric iodide, KIAuIj; then a dark-green
precipitate of auric iodide, very instable, decomposed in pure
water," forming the yellow aurous iodide. (Prescott and
Johnson's Qualitative Chemical Analysis, 4th ed., 154.)
Probably the organic matter present also tends to the reduc-
tion and precipitation of the gold. The physician should be
notified of the change which takes place. Only a very small
amount of menthol is dissolved.

lot.

The usual maximum dose of the fluid extract of digitalis
is two minims, some authorities giving it as high as three.



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I90 INCOMPATIBILITIES IN PRESCRIPTIONS.

In this prescription it is about three and a half minims.
Taking into consideration the frequency of the dose and that
digitalis is cumulative, the pharmacist should decline to fill it
until he has consulted the prescriber, or ascertained that it is an
urgent case.

108.

No apparent change takes place at first but in less than
four hours a yellow-brown precipitate of metallic gold forms.
The arsenous acid reduces the gold chloride. It is also easily
reduced by many other inorganic compounds as well as by
organic matter and light.

104.

Tincture of iron if not too strongly acid will give a color
varying from a blue to a dirty green with morphine. This
color is destroyed by excess of acid or by alcohol. This
prescription will give a bluish-green mixture, which will turn
to a yellowish orange in a day or two. This latter change is
probably due partly to the slow formation of chlorine by the
action of the hydrochloric acid in the tincture on the potas-
sium chlorate. Chlorine turns a morphine solution orange
color. There is not enough water to dissolve aJl of the
chlorate.

105.

Sodium bromide precipitates the codeine salt, ammonium
chloride does not. The phenacetin is not dissolved. The
mucilage will keep the codeine and phenacetin suspended so
that the prescription can be dispensed as a shake mixture.

106.

If the sulphate of iron is strictly ferrous, no liberation of
iodine takes place when a solution of potassium iodide is
added to it, but most of it contains some ferric salt which
liberates iodine. If the morphine is now added it will be



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INCOMPATIBIUTIES IN PRESCRIPTIONS. 191

precipitated by the iodine. The solution of ferrous sulphate
gradually deposits a precipitate of subsulphate of iron. Or
if the solution of ferrous sulphate and the morphine are mixed
before adding the potassium iodide no free iodine is formed,
the morphine seeming to reduce the ferric sulphate to ferrous.

107.

In massing these two chemicals with an excipient containing
water reaction takes place, with the liberation of carbon dioxide,


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