Understanding the Multidimensional Effects of Polymorphism, Particle Size and Processing for D-Mannitol Powders

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• D-mannitol is a key excipient in oral solid dosage forms.
• Mannitol exists in three polymorphic forms: beta (most stable), and delta (kinetically stabilized).

Purpose of the Study:

• To investigate the influence of mannitol's polymorphic form, particle size, and processing on the mechanical properties of solid oral dosage forms.
• To assess the manufacturability of spray granulated beta D-mannitol, beta D-mannitol, and delta D-mannitol.

Main Methods:

• Characterization of particle and powder properties of different mannitol forms and their spray granulated variants.
• Evaluation of tableting properties through direct compression and roller compaction.
• Analysis of the relationship between powder/granule characteristics and tablet mechanical properties.

Main Results:

• Delta-mannitol showed better tableting properties than beta-mannitol in direct compression and after roller compaction.
• Spray granulated beta-mannitol outperformed both delta and standard beta-mannitol in tableting.
• Superior performance of spray granulated beta-mannitol was attributed to its higher specific surface area, enhancing interparticle bonding.

Conclusions:

• Surface characteristics and preprocessing methods can be more critical than polymorphism for the manufacturability of oral solid dosage forms.
• Optimizing particle properties through techniques like spray granulation can enhance the tableting performance of mannitol excipients.