Dr Md Anawar Hossain
What are excipients used in medicine?
Pharmaceutical formulation of a drug product consists of the active pharmaceutical ingredient (API) and excipients. The excipients are called inactive ingredients. According to the U.S. Food and Drug Administration (FDA), the excipients are “any component of a drug product other than an active ingredient”. Most of the drugs (pill, liquid or injectable) contain a relatively small amount of their active pharmaceutical ingredient by mass, while the rest of composition includes inert ingredients or excipients, such as preservatives, dyes, antimicrobials and other compounds. These supposedly inert ingredient may potentially be biologically active causing unanticipated side effects, according to a preliminary new study by researchers from the UC San Francisco School of Pharmacy and the Novartis Institutes for BioMedical Research (NIBR). Their new study was published online in Science, July 23, 2020 (Weiler, 2020).
- They systematically screened 3,296 excipients contained in the inactive ingredient database, and identified 38 excipient molecules that interact with 134 important human enzymes and receptors.
- Their study did not look for actual effects on human patients,
- They only intended to flag molecules with the potential to pose negative health effects,
- It needs to be further studied to understand how they might contribute to side effects of drugs in which they are found.
Why excipients are used in medicine
Excipients are used in medicine to increase
- product shelf stability and preservation,
- maintaining tonicity,
- facilitating drug delivery,
- ensuring the development of the most efficacious medicine,
- avoiding immunogenic or other side effects,
- Delivering medicine safely and effectively,
- Distinguishing pills by color.
Problems in use of excipients
The use of these additive materials may have potential implications for clinical consideration. The safety risk of excipients should be assessed considering their type and variability (Ionova and Wilson, 2020).
- Excipient termed as inactive” ingredients are not as inert as the name suggests.
- Excipient complexity has been identified in 230 biological formulations,
- Excipient-related adverse effects have been identified,
- Most commonly occurring excipients are water, sodium chloride, polysorbate 80, sucrose, and mannitol,
- Many formulations don’t demonstrate the concentration of the most commonly occurring inactive ingredients,
- Literature survey reported some case reports of excipient-related adverse events,
- These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure,
- The use of appropriate excipient in medicine is significant because about 92.8% of oral medicines contain at least one potential allergen in its formulation,
- Inactive ingredients in parenterally administered medicines have been associated with increased sensation of pain at the injection site,
- Some inactive ingredients have been identified as the potential factors impacting immunogenicity of biologics,
- These ingredients can exert adverse effects on sensitive and intolerant people, particularly on vulnerable pediatric and elderly people, who have serious and life-threatening diseases and they need treatment with unstable biological medicines.
Biologic drug product
The formulation development of biological drug products has some difficulties due to their complexity and fragility (Ionova and Wilson, 2020).
- First, stability and preservation present a significant challenge as the API of a biologic is more unstable than in small molecule drugs.
- Protein-based therapeutics have a potential to cause an immunogenic response leading to adverse events that are often not discovered until after the medicine is on the market.
- Most of these medicines must be developed in a liquid form for compatibility with subcutaneous, intramuscular, or intravenous administration.
Present and future of biologics
- The biologics are the fastest growing drug products in spite of the challenges in formulation development,
- The development of biosimilar formulations is expanding rapidly due to the anticipated patent expirations of many biologics,
- The U.S. FDA defines a biosimilar as a “biological product that is highly similar to the reference product notwithstanding minor differences in clinically inactive components and that has no clinically meaningful differences in terms of safety, purity or potency from an existing FDA-approved reference product”.
References
Ionova Y, Wilson L (2020) Biologic excipients: Importance of clinical awareness of inactive ingredients. PLoS ONE 15(6): e0235076.
Weiler, N (2020) Some Inert Drug Ingredients May Be Biologically Active. Comprehensive Laboratory Study Flags Drug Components in Need of More Rigorous Review, July 23, 2020. Link: https://www.ucsf.edu/news/2020/07/418146/some-inert-drug-ingredients-may-be-biologically-active. Accessed on 20/05/2022.
