Drug-Excipient Interactions: An Overview on Mechanisms and Effects on Drug Stability and Bioavailability

Abstract

Drugs are administered as medicines or drug products which are composed of active substance and excipients. Excipients are not inert materials, they can interact with the active substance or with other materials in the surroundings. In this review, drug-excipient interactions (DEI) will be reviewed in two parts. In this first part, a definition of DEI will be proposed. The classification systems will be reviewed, however, the main classes, namely, chemical, physical, and biopharmaceutical will be defined and subclassified accordingly. Physical interactions occur mainly in three forms: complexation, adsorption, or solid dispersions. Chemical interactions occur mainly as hydrolysis, oxidation, Maillard reaction, isomerization, or polymerization. Biopharmaceutical interactions occur after drug administration and mainly affect the pharmacokinetics of the drugs. All these interactions will be defined and explained through the many examples picked from the up-to-date literature. The impact of such interactions on drug release from dosage forms, drug stability in the dosage forms, drug dissolution, absorption, and bioavailability after administration to patients will be briefly explained.