Thursday, 20 June 2013

Pharmacy Incompatibility: Physical Incompatibility

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.

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.

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