Drug Incompatibility Pharmaceutical incompatibility of a drug refers to interactions between two or more substances which lead to changes in chemical, physical and therapeutic properties of the drug or its dosage form.Incompatibilities are usually unintentional.
Incompatibility occurs as a result of mixing of two or more “Antagonistic Substances” & an undesirable product is formed which may affect the safety, efficacy & appearance of the pharmaceutical preparation.
It may occur in vitro between drugs & other components during preparation, storage or administration.
Types of Drug Incompatibility
There are three types of drug incompatibilities-1. Therapeutic incompatibility
2. Physical incompatibility
3. Chemical incompatibility
Therapeutic Incompatibility
It is the modification of the therapeutic effect of one drug due to the prior concomitant administration of another, or it may occur due to overdose or wrong dose of the drug being prescribed. Basically the interaction can alter the pharmacokinetic or pharmacodynamic property of the drug.
Pharmacokinetics interactions involve alteration of absorption, distribution, metabolism and excretion of the drug
Pharmacodynamics interactions involve modulation of pharmacological response resulting in synergistic, antagonistic, potentiation or additive response. This can also lead to altered cellular drug transport.
Examples:
1. Tetracycline interacts with milk forming unabsorbed complex (altered absorption).
2. Antibiotics kill large number of normal flora of intestine, thus drugs like digoxin when given with antibiotics, toxicity appears due to altered metabolism of digoxin.
3. Sulphonamide displaces warfarin thus leading to bleeding (altered distribution).
4. Penicillin and tetracycline are weak acid and are unionized in acidic pH thus are reabsorbed in the body (altered excretion)
5. Caffeine oral increases and chloral hydrate oral decreases sedation and drowsiness, thus two should not be prescribed together.
Examples:
1. Benzalkonium chloride and sodium lauryl sulfate when are mixed, a precipitate is formed because benzalkonium chloride is positive charged while sodium lauryl sulfate has negative charge.
2. A prescription containing Ephedrine sulfate, menthol and liquid paraffin is incompatible due to ephedrine sulphate , a salt soluble in water not in organic solvents, oil and paraffin.
Immiscibility appears in emulsion, creams, lotions and ointments In can happen due to incomplete mixing, addition of surfactants, presence of microorganism or change in temperature. Liquefaction, a physical incompatibility occurs when two solid substances are mixed together, conversion to a liquid state takes place.
The reasons for liquefaction are
(i) When the solid substance is soluble in another solid substance, decrease of its melting point and conversion to a liquid take place.
(ii) By mixing hydrated crystals and dry crystals, crystalline water diffuses to dry crystals leading to formation of liquid.
Chemical incompatibility is a reaction between two or more substances which lead to change in chemical properties of drug or its pharmaceutical dosage form. It can occur due to oxidation, hydrolysis, polymerization, isomerization, decarboxylation, absorption of CO2, combination or formation of insoluble complexes.
Chemical incompatibility is of two types:
Tolerated Chemical Incompatbility:
The incompatability is minimized by changing the order of mixing not the components.
Adjusted Chemical Incompatability:
Here addition or substitution of interacting component is done without affecting the efficacy. In sodium salicylate mixture, syrup of lemon is used as flavorant, it reacts with sodium salicylate, forming an insoluble salicylic acid, thus instead of syrup of lemon, tincture of lemon can be used.
Some other examples of such type of incompatibility include:
Examples:
1. Phenylephrine shows change in color due to oxidation.
2. Penicillin G sodium is affected by acidic condition created syrup of cherry and thus an indiffusible penicillinoic acid is formed which is an inactive product.
3. Potassium chlorate-tannic acid formulation is explosive, therefore minimal rubbing is required 4. Sodium bicarbonate-borax-glycerin preparation leads to evolution of carbon dioxide, therefore formulation must be dispensed once the gas is ceased down.
Intentional incompatibilities are observed in some prescriptions, which are done to modify the activity of one in presence of other.
Examples:
1. Atropine and morphine prescribed together, the former should antagonize the depressant effect of morphine to the respiratory tract.
2. A 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.
3. Tincture myrh is diluted with water to give a precipitate which is used as a gargle in the treatment of tonsillitis.
Examples:
1. Tetracycline interacts with milk forming unabsorbed complex (altered absorption).
2. Antibiotics kill large number of normal flora of intestine, thus drugs like digoxin when given with antibiotics, toxicity appears due to altered metabolism of digoxin.
3. Sulphonamide displaces warfarin thus leading to bleeding (altered distribution).
4. Penicillin and tetracycline are weak acid and are unionized in acidic pH thus are reabsorbed in the body (altered excretion)
5. Caffeine oral increases and chloral hydrate oral decreases sedation and drowsiness, thus two should not be prescribed together.
Physical Incompatibility
Physical incompatibility is the result of interaction between two or more substances which lead to change in color, odor, taste, viscosity and morphology. It can occur due to insolubility of prescribed agent in vehicle, immiscibility of two or more liquids or liquification of solids mixed in a dry state (called eutexia). The solubility of the drug can be altered due to change in pH, milling, use of surfactant, chemical reaction, complex formation and co-solvent used.Examples:
1. Benzalkonium chloride and sodium lauryl sulfate when are mixed, a precipitate is formed because benzalkonium chloride is positive charged while sodium lauryl sulfate has negative charge.
2. A prescription containing Ephedrine sulfate, menthol and liquid paraffin is incompatible due to ephedrine sulphate , a salt soluble in water not in organic solvents, oil and paraffin.
Immiscibility appears in emulsion, creams, lotions and ointments In can happen due to incomplete mixing, addition of surfactants, presence of microorganism or change in temperature. Liquefaction, a physical incompatibility occurs when two solid substances are mixed together, conversion to a liquid state takes place.
The reasons for liquefaction are
(i) When the solid substance is soluble in another solid substance, decrease of its melting point and conversion to a liquid take place.
(ii) By mixing hydrated crystals and dry crystals, crystalline water diffuses to dry crystals leading to formation of liquid.
Chemical Incompatibility
Chemical incompatibility is a reaction between two or more substances which lead to change in chemical properties of drug or its pharmaceutical dosage form. It can occur due to oxidation, hydrolysis, polymerization, isomerization, decarboxylation, absorption of CO2, combination or formation of insoluble complexes.Chemical incompatibility is of two types:
Tolerated Chemical Incompatbility:
The incompatability is minimized by changing the order of mixing not the components.
Adjusted Chemical Incompatability:
Here addition or substitution of interacting component is done without affecting the efficacy. In sodium salicylate mixture, syrup of lemon is used as flavorant, it reacts with sodium salicylate, forming an insoluble salicylic acid, thus instead of syrup of lemon, tincture of lemon can be used.
Some other examples of such type of incompatibility include:
Examples:
1. Phenylephrine shows change in color due to oxidation.
2. Penicillin G sodium is affected by acidic condition created syrup of cherry and thus an indiffusible penicillinoic acid is formed which is an inactive product.
3. Potassium chlorate-tannic acid formulation is explosive, therefore minimal rubbing is required 4. Sodium bicarbonate-borax-glycerin preparation leads to evolution of carbon dioxide, therefore formulation must be dispensed once the gas is ceased down.
Intentional Incompatibilities
Intentional incompatibilities are observed in some prescriptions, which are done to modify the activity of one in presence of other.Examples:
1. Atropine and morphine prescribed together, the former should antagonize the depressant effect of morphine to the respiratory tract.
2. A 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.
3. Tincture myrh is diluted with water to give a precipitate which is used as a gargle in the treatment of tonsillitis.
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