Raising Expectations Of Excipients

Excipients have never shared the limelight with active pharmaceutical ingredients (APIs), nor have they historically been given the credit that they deserve in drug development, manufacturing, and delivery. An excipient’s role has traditionally been viewed as merely a filler or binder contributing to the stability of the end product.

The full value that a formulation can bring to a final dosage form; or the real importance of ensuring an excipient’s quality and performance; are often underestimated, overlooked, misunderstood, or disregarded. In reality, the functionality of the excipient can help determine whether or not a drug succeeds or fails.

The possible consequences of not carefully choosing the best excipient for your formulation include manufacturing complications, compromised stability, poor bioavailability of the API, unintended side-effects, reduced shelf-life of the finished product, and even serious adverse reaction or death of the patient. This seems the ultimate irony when therapies and pharmaceuticals are intended to help patients and improve their well-being, not harm them. To avoid these undesirable outcomes, what can you do to select the right excipient for your formulation and guarantee its quality?

While the pharmaceutical industry has been strictly regulated for years, excipients serve multiple industries as common food and cosmetic ingredients, and are often perceived only as processing aids or “inactive” additives. Because of this, regulations regarding excipients can be less stringent and regionally fragmented. It’s no wonder that there is confusion about excipients and that if the misguided motivation is there, loopholes can be found to substitute or otherwise misrepresent them.

While excipient regulation has unarguably been inconsistent, decentralized, and not in synch with the rest of the pharmaceutical industry, recently there have been more focused efforts toward harmonization and standardization of pharmaceutical excipient regulations, as well as progress toward accredited certification of manufacturing procedures. These heightened efforts can be attributed to several well-documented accidents caused by adulteration of excipients and a growing appreciation for them as important functional or enabling ingredients that contribute to the ultimate success or failure in the final dosage form.

Excipients play important roles in delivery, manufacture and performance of medications. Dosage form design programmes involve choosing the most appropriate excipients, their optimum inclusion levels and the best mode of incorporation in the product. However, interactions between a drug and the excipients with which it is co-formulated in a medication can compromise the quality, efficacy or even safety of the product. Such effects may be due to direct drug: excipient interactions or reactions between drug and residues or impurities in the excipient. These may lead to the formation of new molecular constructs (degradation products) or a changed physical form of the drug. Drug substance characterization and dosage form design programs need to be explore such interaction possibilities to help choose excipients that are compatible with the drug. such investigations will reduce the risk of problems arising later in the program as instability often takes some time to be manifest.