Functional Excipients

FORMULATION FORUM - Age-Appropriate Pediatric Formulation Development

Jim Huang, PhD, reviews how a pediatric formulation should consider the following factors: difference in physiological and pharmacokinetic of patient populations, dosage form selection, route of administration, dose accuracy, dose flexibility, drug and excipient tolerability (safety and toxicity), patient compliance (palatability/swallowability), stability, and drug accessibility.

FORMULATION FORUM - Application of Captisol® Technology to Enable the Formulation of Remdesivir in Treating COVID-19

James Pipkin, PhD, Vince Antle, PhD, and Rebecca Garcia-Fandiño, PhD, explain why more Captisol® than ever is required to meet Gilead’s bold goals of making remdesivir available to COVID-19 patients in the US and to hundreds of countries around the world.

What are functional excipients?

The global pharmaceutical excipients market was valued at $7.7 billion in 2020 and is expected to reach $11.2 billion by 2026. Functional excipients are witnessing a strong demand as companies supply a wide range of functional excipients that help manufacturers produce cost-effective, high-quality, finished pharmaceutical product. Many industry experts point to a widening demand and use of organic pharmaceutical excipients. These organic excipients include oleochemicals, petrochemicals, proteins, carbohydrates, and others. Additionally, binders and functional excipients are witnessing a strong demand. Regarding delivery route, it is the topical segment that is witnessing fast growth in the global pharmaceutical excipients market, as topical drug delivery is witnessing a significantly stronger progression be­cause of its ability to surpass the metabolism pathways of the stomach and liver.

However, the high cost associated with the drug development process will impede the growth rate of the pharma­ceutical excipients market. Additionally, strict government regulations have hindered the pharmaceutical excipients market growth. Safety, quality concerns, and lack of awareness will further challenge the market in the forecast period mentioned above.

This is particularly true for novel excipients, which do have technical, therapeutic, and commercial benefits in oral drug delivery. Despite their formulation-enhancing benefits, novel excipients are sacrificed early in development because of a lack of prece­dence of use.

Without an independent path­way to allow new excipients or new uses for existing excipients into drug products, except when associated with a drug filing, there are limited tools available for pharmaceutical compa­nies to formulate better performing, and in many cases, life-saving drugs. Meanwhile, drug manufacturers are reluctant to use new excipients and take on the additional layer of scrutiny from regulatory agencies to demonstrate full excipient characterization, safety, quality, func­tion, and appropriateness of use.

Functional Excipients and the FDA

The Food & Drug Administration (FDA) has acknowledged that the lack of novel excipients is indeed a prob­lem. In September 2021, the Agency announced the Novel Excipient Review Pilot Program, which will select and re­view four novel excipients in the next two years using a new pathway. This will allow manufacturers to obtain an FDA review prior to the use of the novel excipient in a drug formulation.

The FDA’s recent stance and accept­ance that the novel excipients are crit­ical in development of new drug candidates, the perceptions around the novel excipients are being changed as the Agency continues to embrace the facts that the pharma in­dustry is in dire need of new excipients for bringing the innovative drugs to the market faster. This is the first time in history that the agency is opening doors for novel ex­cipients to be freely evaluated and used in the innovative formulations for NCEs.

Note, though, that this is not an excipient approval process; the novel excipient would still be evaluated as part of the overall drug product ap­proval. In the next 3 to 5 years, we can expect to see an accel­eration in the examination of the com­position and purity of excipients.