Tablet Binding: Causes, Analyses, and Strategic Avoidance

The tablet is the most versatile dosage form in the pharmaceutical field due to its small size and excellent portability and ingestibility. Tablets are the most commonly used oral solid preparations, and are manufactured by compressing powders containing an active ingredient and excipients. In the manufacturing process, some materials from the tablet may adhere to the die wall, and tableting failures from damage due to binding may occur at the sides of the tablet. The definition and mechanisms of binding, the advantages of various assessment methods, and the current challenges and progress of assessment methods are comprehensively reviewed herein. Efforts to predict the risk of binding have been attempted using a multi-functional compaction instrument, tableting simulators, and simulations based on physicochemical parameters. Several analytical approaches have been applied as conventional evaluations for binding, such as visual observations of the tablet and die wall, measurements of ejection stress, differences between upper and lower punch forces, and die wall stress. However, these evaluation methods cannot always provide both qualitative and quantitative information and, thus, a more reliable evaluation strategy is desired. A newly-developed qualitative and quantitative evaluation method for powder adhesion to the die wall after tableting, named Binding Identification for Net Detriment (BIND), and its various applications to avoid binding are also reviewed herein. This review also focuses on the analytical performance and reliability of binding evaluations for commercial production.