Pharmaceutics Incompatibility & Dr.

Azaa Amr FaYed

Incompatibilities:
The term incompatibility applied to prescriptions when problems arise during the
compounding, certain dispensing, or administration because of their physical, chemical or
therapeutic properties.

Types of incompatibilities
(A) Therapeutic incompatibilities
(B) Physical incompatibilities
(C) Chemical incompatibilities
They are those in which an apparent inconsistency
occurs in the drugs or dosage prescribed.
They are those in which the physical properties of the
ingredients produce a mixture unacceptable in
appearance or inaccuracy of dosage.
They are those in which two or more ingredients react
to give new compounds.

Importance of Determining Incompatibility:

Incompatible products may affect
 Safety of medicament.
 Efficacy of product.
 Appearance of a medicine.
 Purpose of medication.
Therapeutic incompatibility

Therapeutic incompatibilities may be classified as: (4 type)

1. Dosage error
 Result from the administration of a single high dose, or the too frequent administration
Rx:  Maximum Daily dosage of Atropine is 2mg
Atropine Sulphate 6 mg  Represents 12 times the dose of atropine and
Phenobarbital 360 mg phenobarbital.
Ft. caps, I mitte xii  The physician undoubtedly intended that the
Sig: caps, I t.d.s prescription be divided into 12 doses but wrote the
wrong directions
 It is necessary to call the prescriber and request permission to correct the directions
(Atropine sulphate 0.5 mg and Phenobarbital 30 mg)
(2) Additive and synergistic combinations

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Pharmaceutics Incompatibility & Dr. Azaa Amr FaYed
If several drugs having the same pharmacological action are prescribed together  near
their full or maximum individual dose
 Drugs of such combinations should be prescribed in reduced amounts because the
sum of their therapeutic activity may be too great

Examples of useful synergistic effect

1. Combinations of sulfonamides
2. Neomycin + Erythromycin
3. Aspirin + codeine
Show less nephrotoxicity than a single sulfonamide.
Has a broader spectrum than using antibiotic alone.
Combination reduces the amount of expensive
codeine required

(3) Antagonistic combinations:

Antagonism means that the therapeutic action of one drug is cancelled by administration of
another drug

Examples:
(1) Stimulants with sedatives (depressant) Ex: Caffeine with chloral hydrate
(2) purgative with antidiarrheal Ex: Mgso4 with tannins
Acidifiers with alkalinizers Ex: Aspirin with AL (OH)3.
(4) Contraindicated drugs
Sometimes combination increases the action and toxicity of potent drug.

Examples
(1) The administration of tetracycline with food as milk or drugs containing calcium ions
is prohibited due to the formation of non-absorbable complex
(2) Inactivation of sulfa drugs by procaine HCI.

Physical incompatibility
These incompatibilities produce a mixture which is unacceptable in appearance and taste and
may result in non-uniform dosage form.

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Pharmaceutics Incompatibility & Dr. Azaa Amr FaYed
(1) Incomplete solution or insolubility
When two or more substances are combined, not give a homogenous product owing to
immiscibility or insolubility

 Sometimes the physician may prescribe the wrong solvent.

 Gums are insoluble in alcohol
 Resins are insoluble in water
 Oils are immiscible in water
Example:

RX: Terpin hydrate is insoluble in this vehicle thus: half of the

Terpin Hydrate 3.0 gm syrup may be replaced by alcohol.
Simple Syrup 120 ml

Terpin hydrate is an expectorant, used to dissolve mucus in patients presenting with acute or
chronic bronchitis
(2) Precipitation
A substance is generally precipitated from its solution in one solvent if another solvent in
which it is insoluble is added

Examples
(1) Resins are precipitated from alcoholic solution when water is added
(2) Camphor and volatile oils are salted out from their aromatic water when soluble salts
are added

(3) Separation or immiscible liquid

When certain substances are mixed together, an immiscible liquid floats the surface.

Rx: Phenol 2% Example:

Sod Sulphate 5%  P henol will be salted out by sodium sulphate.
Distilled water to 100 ml  A clear solution obtained if the phenol is dissolved in 10 ml
Ft. Solution Sig m.d.s glycerin and the sodium sulphate added as a dilute aqueous
solution

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(4) Eutaxia ‫مهم‬
 Liquefaction of solid ingredients when mixed together)
 The term eutectic mixture is applied when two powders are mixed together in a certain
proportion to give the lowest melting point
 Ex: a mixture of 45% camphor and 55% salol
Methods of Rectifying Liquefaction:
 By the use of absorbent like kaolin, light magnesium carbonate.

Correction (Physical incompatibilities) By one or more methods

 Order of mixing
 Alteration of solvents
 Change in the form of ingredients
 Alteration of volume
 Emulsification and addition of suspending agent
 Addition, substitution or omission of therapeutically inactive substances.

Chemical incompatibility

It exists when the ingredients of a prescription undergo a chemical reaction result of oxidation
reduction, acid base, hydrolysis, or combination reactions
Examples (3 Type): - Formation of precipitate - evolution of gas - colour change

(1) Formation of precipitate:

Interaction between two soluble substances may produce an insoluble product

 Precipitation is unfavorable in prescriptions because it is difficult to obtain a uniform

dose even after shaking the bottle and also solid materials are usually slower in
action when administered in solution.

(2) Evolution of a gas:

Prescriptions containing carbonates or bicarbonates and acids such as citric, acetic and
tartaric acid effervesce on mixing.

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 This incompatibility can be overcome by allowing the reaction to complete in an open-

mouthed container.
Example:
Rx: Amm. Carb + acetic acid CO2
Amm. Carbonate
Amm. Chloride Solution
Acetic acid In a wide mouthed bottle, add ammonium carbonate and acetic
Syrup of cherry acid mix till effervescence ceases. Add ammonium chloride and
Fait solution complete the volume with syrup of cherry.
Ammonium carbonate as an active ingredient intended to help relieve symptoms of
bronchitis

(3) Color change

The color change is evidenced by a chemical reaction.
 The color change, is of no significance from the therapeutic point of view. But a
psychological effect on the patient
Examples
 Epinephrine solution turns brown by oxidation becomes inactive and it must be
rejected
 Salicylate acquires a reddish color or pinkish color on Keeping

Intentional Incompatibilities

(1) Therapeutic intentional incompatibilities

In many cases antagonistic combinations are intentional.

Examples:
(1) Atropine should antagonize the depressant effect morphine to the respiratory tract
(2) Central nervous system stimulants may be used to overcome the drowsiness
produced by anti-histaminic

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(3) 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

(2) Chemical intentional incompatibilities

Example:
1. Black wash contains glycerin, calomel (HgCl2) and lime water (Calcium Hydroxide).
2. Mercurous chloride with lime water gives a black precipitate of HgO and Hgo
which is desired in treatment of syphilitic ulcers.

(3) Physical intentional incompatibilities

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

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