Pharmaceutical incompatibility is an interaction between two or more substances that results in an undesirable change in the drug’s safety, efficacy, stability, and/or appearance. It may involve the active ingredients and/or excipients. There are three types of incompatibilities: physical, chemical, and therapeutic.
When an interaction between two or more substances causes an undesirable physical change in the product, the process is called physical incompatibility. It changes color, odor, taste, texture, viscosity, and appearance. It also changes the product’s physical properties, like solubility, precipitation, and liquefaction. Physical incompatibilities may make it difficult to measure the drug dose accurately. Examples include - castor oil, which is immiscible in water, so it is difficult to make an emulsion; when menthol and camphor, which are present in a solid state, are mixed together, they liquefy; alcoholic solutions of tincture benzoin, which contains resins, precipitate when mixed with water.
A reaction between two or more substances leading to an unwanted change in the chemical properties of the pharmaceutical product is called chemical incompatibility. The types of chemical reactions include oxidation, hydrolysis, polymerization, decarboxylation, absorption of carbon dioxide, isomerization, and formation of insoluble complexes. These changes can be noticed as turbidity, color changes, effervescence, and precipitation. Shaking a solution well before use may help to remedy certain chemical incompatibilities. Cardiac glycosides, like digoxin, are hydrolysed by acids or alkalis to form poisonous precipitates. Similarly, antibiotics precipitate with acids, alkalis, and heavy metals to inactive metabolites.
Therapeutic incompatibilities are unintentional pharmacodynamic or pharmacokinetic interactions that occur in vivo after administering two or more drugs. As a result, the therapeutic effect of one or more drugs changes, such as a decrease or complete loss of drug effect, toxicity, or the appearance of new adverse effects. Causes of therapeutic incompatibilities include error in dosing, incorrect dose or dosage form, synergism or antagonism, drug interactions, and administration of contraindicated drugs at the same time.
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