Definition:
Pharmaceutical incompatibility refers to undesirable interactions between drugs or between a drug and its excipients (non-active ingredients) that can affect the safety, efficacy, or stability of a pharmaceutical product.
These incompatibilities can occur during the formulation, storage, or administration of drugs, leading to changes in physical appearance, chemical stability, or therapeutic effect.
Classification of Pharmaceutical Incompatibilities:
Pharmaceutical incompatibilities can be classified into three main types:
Physical Incompatibility
Definition: Occurs when physical changes in appearance or properties (such as solubility, color, or texture) are observed without any chemical reaction between the components.
Examples:
Precipitation: When two solutions are mixed, and an insoluble precipitate forms.
Immiscibility: When two liquids do not mix (e.g., oil and water emulsions).
Liquefaction of powders: Certain powders may liquefy upon mixing due to moisture absorption (eutectic mixtures).
Common Causes: Changes in solubility, particle size, pH, or mixing of incompatible solvents or excipients.
Chemical Incompatibility
Definition: Occurs due to a chemical reaction between the drug and other ingredients, resulting in degradation, loss of efficacy, or the formation of toxic by-products.
Examples:
Oxidation: Drug degradation due to exposure to oxygen (e.g., ascorbic acid).
Hydrolysis: Breakdown of drugs due to reaction with water (e.g., esters or amides).
Complexation: Drug interaction leading to the formation of complexes that reduce drug availability (e.g., tetracyclines with calcium or magnesium).
pH-dependent degradation: Drugs sensitive to pH changes, like aspirin, can degrade into inactive forms.
Common Causes: Exposure to light, heat, moisture, pH changes, or reaction with excipients.
Therapeutic Incompatibility
Definition: Occurs when two or more drugs administered together produce undesirable pharmacological effects or reduce each other's efficacy.
Examples:
Synergistic effects: Combined drugs may lead to an exaggerated response, resulting in toxicity (e.g., alcohol and sedatives).
Antagonistic effects: One drug may reduce or negate the effect of another (e.g., antacids reducing the absorption of antibiotics).
Altered absorption, distribution, metabolism, or excretion: One drug may interfere with the pharmacokinetics of another (e.g., warfarin and certain antibiotics).
Common Causes: Drug interactions due to pharmacodynamic or pharmacokinetic interference, administration route, or timing of drug intake.