Formulating a Stable Mannitol Infusion while Maintaining Hyperosmolarity.

Area of Science:

• Pharmacology
• Neuroscience
• Materials Science

Background:

• Mannitol infusion is a standard treatment for intracranial hypertension after traumatic brain injury.
• Mannitol solutions exceeding 10% w/v are prone to recrystallization under ambient conditions, compromising stability.
• Recrystallization can occur unpredictably during storage or administration, posing clinical risks.

Purpose of the Study:

• To define the stability limits of 20% w/v mannitol infusion, a common clinical concentration.
• To develop novel, stable, and tunable hyperosmotic formulations of mannitol.
• To investigate mannitol's compatibility with other osmotic agents like NaCl, sorbitol, and glycerol.

Main Methods:

• Investigated the recrystallization behavior of 20% w/v mannitol solutions.
• Formulated and characterized new hyperosmotic solutions combining mannitol with NaCl, sorbitol, and glycerol.
• Assessed the stability and tuneability of these novel formulations.

Main Results:

• Characterized the specific stability limits of 20% w/v mannitol infusion.
• Identified several stable and tuneable hyperosmotic mannitol formulations using NaCl, sorbitol, and glycerol.
• Demonstrated the potential for improved safety and efficacy compared to standard mannitol infusions.

Conclusions:

• Standard 20% w/v mannitol infusions exhibit significant stability issues due to recrystallization.
• Co-formulations of mannitol with NaCl, sorbitol, or glycerol offer safer and more stable alternatives.
• These novel formulations provide tuneable osmotic properties for optimized clinical application in managing intracranial hypertension.