Excipients: Background/Introduction
Lokesh Bhattacharyya, Stefan Schuber, Catherine Sheehan,
and Roger William
Department of Standards Development, United States Pharmacopeia,
Rockville, Maryland, U.S.A.
Almost all therapeutic products, including therapeutic products for human and
veterinary use, include excipients—indeed, the total amount of excipients frequently
used is greater than the amount of the active drug substance(s) in a dosage form. As
with drug substances, excipients are derived from natural sources or are synthesized
either chemically or by other means. They range from simple, usually highly characterized,
organic, or inorganic molecules to highly complex materials that are difficult
to fully characterize.
In earlier days, excipients were considered inactive ingredients. Over time,
pharmaceutical scientists learned that excipients are not inactive and frequently have
substantial impact on the manufacture and quality, safety, and efficacy of the drug
substance(s) in a dosage form. Further, variability in the performance of an excipient—both
batch to batch within a single manufacturer as well as between batches
from different manufacturers—came to be understood as a key determinant of
dosage form performance. Excipients are now known to have defined functional
roles in pharmaceutical dosage forms. These include (i) modulating solubility and
bioavailability of the active ingredient(s); (ii) enhancing stability of the active ingredient(s)
in finished dosage forms; (iii) helping active ingredients maintain a preferred
polymorphic form or conformation; (iv) maintaining pH and osmolarity of liquid
formulations; (v) acting as antioxidants, emulsifying agents, aerosol propellants,
tablet binders, and tablet disintegrants; (vi) preventing aggregation or dissociation;
and (vii) modulating the immunogenic response of active ingredients (e.g., adjuvants)
and many others. United States Pharmacopeia 28–National Formulary 23 lists
40 functional categories of excipients for pharmaceuticals, and many more are
expected as new—and usually increasingly complex—drug-delivery systems emerge
and evolve. Approximately 800 excipients are currently used in the marketed pharmaceutical
products in the United States. This number is also expected to grow with
new therapeutic categories, such as gene therapy and cell therapy, and new drugdelivery
technologies