Incompatibilities of Pharmaceutical Excipients with Active Pharmaceutical Ingredients: A Comprehensive Review

Abstract

Studies of drug-excipient compatibility represent an important phase in the pre-formulation stage for the development of all dosage forms. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. The present review covers the literature reports of incompatibilities of commonly used pharmaceutical excipients with different active pharmaceutical ingredients. Examples of drug-excipient interactions, such as transacylation, the Maillard browning reaction, acid base reactions and physical changes are discussed for different active pharmaceutical ingredients belonging to different therapeutic areas viz. antiviral, anti-inflammatory, antidiabetic, antihypertensives, CNS drugs, anti-convulsants, antibiotics, bronchodialators, antimalarial, amtiemetic, vitamins, antiamoebics, antipsychotics, antidepressants, anticancer, anticoagulants and sedatives/ hypnotics. Once solid-state reactions are understood in a pharmaceutical system, the necessary steps can be taken to prevent reactivity and improve the stability of drug substances and products.