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By Ajit S. Narang

Ajit NarangExcipients play a central role in the design of a robust product with a sound control strategy that would conform to meaningful specifications during its lifecycle. Excipient selection during formulation design influences business-critical and clinically significant drug product performance outcomes such as stability, bioavailability, and manufacturability. Therefore, thorough understanding of excipient variability is critical to robust drug product development. Importantly, the International Council on Harmonization (ICH) draws attention to excipient understanding in the ICH guideline Q8(R2), emphasizing the need for enhanced knowledge of product performance over a wide range of material attributes.

Excipients can impact drug product stability by several mechanisms that involve physicochemical drug-excipient and/or excipient-excipient interactions in dosage forms. To obviate any significant drug-excipient interactions, excipient compatibility testing is typically carried out very early in formulation design. Nevertheless, incompatibilities are often observed in drug products, when these incompatibilities are not clearly evident during compatibility testing.

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Excipients can also have unintended effects on the bioavailability of drugs. Excipients can impact oral drug absorption by contributing to or affecting the supersaturation of a drug in the small intestine after oral administration. In addition, they can bind to the drug, thus altering the amount of free drug available for absorption. They can help overcome variability in the oral drug absorption of a compound resulting from drug interaction with the gastrointestinal physiology. Adsorption of drugs onto excipients can alter the rate of drug dissolution, which can impact oral bioavailability. Intimate coprocessing of drugs with excipients, such as by spray drying, coprecipitation, cogrinding, or the formation of solid dispersions, can lead to improvement in drug solubility and/or dissolution rate.

The cover article in the March issue of the AAPS Newsmagazine highlights the role of excipient attributes on drug product critical quality attributes with a view to addressing excipient variability during formulation design and drug product development. Read Addressing Excipient Variability in Formulation Design and Drug Development, from the FDD section, and then participate in the discussion point below.

Have you encountered a problem during drug development that was linked to batch-to-batch variability in an excipient?

Ajit S. Narang, Ph.D., works for the Drug Product Science & Technology department of Bristol-Myers Squibb co. in New Brunswick, N.J. on injectable biologics after receiving his doctorate from the University of Tennessee, Memphis.