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

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Mannitol is a common excipient in oral formulations.
• High concentrations of mannitol can lead to tablet defects during compression.

Purpose of the Study:

• To investigate the relationship between mannitol's material attributes and its mechanical properties.
• To understand how variations in mannitol lots affect tablet compaction performance.

Main Methods:

• Assessed mechanical properties (Poisson's ratio, fracture energy) and performance (ejection force, tensile strength) using a compaction simulator.
• Analyzed material attributes including particle size distribution, crystal form, specific surface area, powder flow, and moisture absorption for four mannitol lots.

Main Results:

• Variability in mannitol lots, particularly primary crystal size and specific surface area, significantly altered mechanical properties.
• These changes in properties correlated with increased ejection force and residual die-wall stresses, potentially causing tablet chipping.

Conclusions:

• Established a clear link between mannitol's fundamental material attributes and its mechanical performance during compression.
• Emphasized the importance of characterizing mannitol lot variability for successful formulation development, especially with high mannitol content.