Vitamins as excipients in pharmaceutical products

Abstract

Excipients are ingredients in pharmaceutical products other than the active ingredient, added to facilitate manufacturing, enhance stability or modulate release and bioavailability. Vitamins are diverse molecules essential for human nutrition that also can fulfil excipient functions. This review focuses on vitamins used as excipients and provides an overview of the functions of vitamins in various pharmaceutical formulations. A thorough search was conducted to understand the current use of vitamins in marketed drug products, concluding that many vitamins are already used as functional excipients. Vitamins are used widely in different dosage forms, including oral, parenteral, and topical formulations, and alongside a broad range of active pharmaceutical ingredients, biologics, and small molecules from different biopharmaceutical classification system classes. Many examples of the use of vitamins to improve the performance of the pharmaceutical formulation in which they are included are presented and the mode of action of vitamins as excipients in the product is reviewed. Furthermore, the potential for future uses of vitamins in pharmaceutical products is highlighted. Lastly, considerations for the use of vitamins as excipients in drug products as well as the regulatory framework are discussed.

Introduction

Excipients are components of a drug product that are not the active pharmaceutical ingredient (API) (Blecher, 1991). The inclusion of excipients in a pharmaceutical formulation facilitates the manufacture and use of the vast majority of drug products. Excipients serve many functions including aiding in drug manufacture, stabilizing the final product, or modulating the release and bioavailability of the API. An excipient can have one or multiple functions in a formulation. Ideally, excipients are pharmacologically inactive, non-toxic, and do not interact with the API or other excipients (Wisher, 2012). Many have important functions that determine the overall efficacy of the pharmaceutical product.

Excipients may interact with the active ingredient, other ingredients in the formulation, or the physiological environment (Rowe et al., 2009). The physicochemical properties of the API, together with the target product profile of the pharmaceutical drug product will determine the specific excipients to be used, taking into consideration the route of administration, dosage form, API dose, frequency of dosing, storage temperature, primary packaging and other factors.
Excipients are selected from different excipient classes based on the desired function in the end-product (Allen and Ansel, 2014; van der Merwe et al., 2020). In the case of parenteral formulations, the excipients required include solubilizers, solvents, co-solvents, surface-active agents and complexation agents to improve or sustain the solubility of the API. pH modifiers, antioxidants, chelating agents, bulking agents, cryo- and lyo-protectants are also needed to safeguard the stability of the API (Akers, 2002). Antimicrobials and preservatives also play a crucial role in ensuring the safety of multiple use parenteral formulations. Taste-masking ingredients, flavors and colorants are also used and are especially important in oral pediatric medicines (Sohi et al., 2004). Furthermore, tonicity-adjusting agents are used to reduce discomfort and irritation during injection, and surfactants, complexing agents, and polymers are used for regulating or extending the drug release profile.

The form of the final drug product affects the excipients required. Solid oral dosage forms are produced with fillers or diluents to bulk up a dosage form, binders to increase cohesiveness and improve integrity of granules and tablets, disintegrants to aid the breakup of the dosage form, and lubricants or glidants to reduce friction in powder blends (Darji et al., 2018; Kestur and Desai, 2016). Further functionality in solid oral dosage forms can be achieved by the addition of coating agents, solubility or permeation enhancers, or excipients that alter the drug release profile of the formulation (Salawi, 2022). Semisolid and liquid oral dosage forms, similar to parenteral dosage forms, require solubilization agents to improve solubility, namely, solvents, cosolvents, surface-active agents and complexation agents, as well as stabilizers like pH modifiers, antioxidants, chelating agents and bulking agents (Akers, 2002). Similarly, excipients for local and topical pharmaceutical products are selected from suitable excipient classes (Elder et al., 2016). Examples of excipient functions and excipient classes in various dosage forms are shown in Fig. 1.

Fig. 1. Examples of functions of different excipient classes in formulations

The use of excipients in medicines is controlled by regulatory bodies. The definition of an excipient given by the FDA and EMA is similar, namely that an excipient is any ingredient or substance intentionally added to a drug or medicine that is not part of the active substance (European Medicines Agency, 2007; Food and Drug Administration and Department of Health and Human Services, 2023a). The EMA states that excipients are considered inactive but can have a known action or effect in certain circumstances (European Medicines Agency, 2007). Furthermore, the International Pharmaceutical Excipients Council Europe notes that excipients “have been appropriately evaluated for safety and are included in a drug delivery system to either aid the processing or to aid manufacture, protect, support, enhance stability, bioavailability or patient acceptability, assist in product identification, or enhance any other attributes of the overall safety and effectiveness of the drug delivery system during storage or use” (The International Pharmaceutical Excipients Council, 2020a).

Vitamins are widely used in pharmaceutical products as excipients, as we discuss throughout this review article. The most well-known function within the vitamins is the antioxidant activity of vitamins C and E (Rowe et al., 2009). Both molecules are used extensively in pharmaceutical formulations to protect the API from oxidation, therefore stabilizing the product and extending its shelf life (Allen, 2020). However, these and other vitamins are able to exert further functions that benefit drug formulations, as is extensively described in the coming sections. Any vitamin intended for use as an excipient must be available at a standard suitable for pharmaceutical products. Table 1 lists different chemical congeners of vitamins, although not all are currently available with pharmaceutical GMP compliance.

For this review, we conducted searches within pharmaceutical databases to identify products currently on the market containing vitamins as excipients. We introduce various use cases of vitamins, discuss the most recent developments on the topic as well as possible future uses of vitamins and derivatives as excipients, highlighting potential novel benefits and functions. We also provide a regulatory overview of the use of vitamins as excipients in pharmaceutical products.

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See here only a cutout of Table 1. of the Chemical congeners of vitamins and CAS numbers.

Anne-Cécile V. Bayne, Jenni Pessi, Julia K. Bird, René T. Stemmler, Margarita Frerichs, Ahmed Besheer, Vitamins as excipients in pharmaceutical products, European Journal of Pharmaceutical Sciences, Volume 206, 2025, 107020, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2025.107020.