Discerning excipient functionality: Lubricants vs. anti-adherents

Excipients play a vital role in tablet manufacturing by fulfilling a range of functions. However, the distinct roles of lubricants and anti-adherents are often confused, potentially leading to formulation challenges. In this study, we show that internally added hydrogenated vegetable oil (HVO) effectively reduces ejection force but exacerbates punch sticking. Thus, while HVO functions well as a lubricant, it does not act as an anti-adherent. These findings highlight the importance of accurately classifying excipients based on their functionality to inform and optimize formulation design.

Introduction

Most drug products cannot be manufactured without the use of excipients [1,2]. Excipients serve a wide range of functions, from stabilizing the active pharmaceutical ingredients (API) to enabling manufacturability and enhancing the texture and taste of the final product [3,4]. Each excipient plays a unique role in the formulation of various dosage forms, making it important to understand excipient functionality early in the formulation development process [5]. This understanding helps prevent potential negative consequences arising from excipient misuse [6]. Additionally, from a regulatory standpoint, a clear classification of excipient functions not only justifies excipient selection but also supports the development of appropriate excipient evaluation methods [7].

To produce tablets of acceptable quality by compression, a formulation must meet several essential criteria: 1) adequate flowability to ensure consistent and reproducible die filling [8]; 2) sufficient interparticle bonding to form mechanically strong tablets upon compression [9]; 3) low ejection force to prevent damage to both the tablets and tooling [10]; and 4) freedom from punch sticking to enable efficient manufacturing [11]. Because most APIs do not possess all of these characteristics, excipients are essential to ensure the successful manufacturing of high-quality tablets [12,13]. In this context, lubricants are commonly incorporated to reduce ejection forces [10,14], whereas anti-adherents are used to mitigate punch sticking [15].

Since lowering ejection forces and preventing punch sticking are distinct objectives in tablet manufacturing, it is essential to differentiate the functions of lubricants and anti-adherents [16]. Some commonly used lubricants, such as magnesium stearate, can perform both functions [11,17]. This dual functionality has contributed to the widespread but incorrect assumption that lubricants inherently possess anti-sticking properties [[18], [19], [20]]. As a result, there is often an unwarranted expectation that lubricants alone can prevent punch sticking [21,22]. Although it is conceivable that a lubricant does not necessarily act as an anti-adherent, no systematic studies have been published to substantiate this distinction. In this work, we show that, while effective in reducing ejection force, a lubricant may induce severe punch sticking issues, contrary to the expected role of an anti-adherent.

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Materials

Acetaminophen (APAP, Form I) was purchased from Sigma Aldrich (St Louis, MO USA). Hydrogenated vegetable oil (HVO, Lubritab®, JRS Pharma (Patterson, NY), microcrystalline cellulose (Avicel PH102, FMC Biopolymer, Philadelphia, PA), and lactose monohydrate (#316 Fastflo® NF, Foremost Farms, Clayton, WI), Crospovidone (Kollidon CL; BASF; Ludwigshafen, Germany) were obtained from respective manufacturers. Three formulations of APAP (Table 1) were used to evaluate the lubricating efficiency and…

Tianyi Xiang, Changquan Calvin Sun, Discerning excipient functionality: Lubricants vs. anti-adherents, Journal of Drug Delivery Science and Technology, Volume 112, 2025, 107295, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107295.

Read also our introduction article on Lubricants here: