Effect of Material Properties and Variability of Mannitol on Tablet Formulation Development.

Purpose: Using a high level of mannitol as a diluent in oral formulations can potentially result in tablet defects (e.g., chipping, cracking) during compression. This work aims to scrutinize the linkage between the mechanical properties and material attributes of mannitol and also uncover how variations between vendors and lots can lead to significant changes in the compaction performance of tablet formulations containing mannitol. Methods: The mechanical properties (Poisson's ratio, fracture energy) and mechanical performance (ejection force, pressure transmission ratio, residual radial die-wall stress, and tensile strength) of mannitol compacts were assessed on a compaction simulator for four lots of mannitol from two different vendors. The variation of material attributes of each lot, including particle size distribution (PSD), crystal form, primary crystal size and morphology, specific surface area (SSA), powder flow, and moisture absorption were investigated. Results: The variability of material attributes in mannitol lots, especially primary crystal size and SSA, can result in significant changes in mechanical properties and mechanical performance such as ejection force and residual radial die-wall stresses, which potentially led to chipping during compression. Conclusion: The study elucidated the linkage between fundamental material attributes and mechanical properties of mannitol, highlighting their impact on tablet defects and compaction performance in compression. A comprehensive understanding of the variability in mannitol properties between vendors and lots is crucial for successful formulation development, particularly when high percentages of mannitol are included as a brittle excipient. [ABSTRACT FROM AUTHOR]