Abstract
Mannitol infusion is commonly used in the treatment of intracranial hypertension following traumatic brain injury. It has long been known to have stability issues, specifically, mannitol recrystallises from solutions greater than 10% w/v in ambient conditions. This can happen at any time, whether on the pharmacy shelf or during a medical procedure. This study describes the stability limits of 20% w/v mannitol infusion (the most common strength used clinically) and proposes a number of safer, stable and tuneable hyperosmotic formulations of mannitol in combination with clinically acceptable osmotic agents (NaCl, sorbitol and glycerol).
Highlights
Traumatic brain injury (TBI) is one of the greatest causes of death and disability in those aged under 40 [1], and with 69 million cases of TBI each year [2], this presents a critical health problem
We have evaluated a number of hyperosmolar alternatives which could be directly translated to the clinic
Formulation approaches to achieve the target of 1098 mOsmol·L−1
Summary
Traumatic brain injury (TBI) is one of the greatest causes of death and disability in those aged under 40 [1], and with 69 million cases of TBI each year [2], this presents a critical health problem. The pathological mechanism behind this death and disability (besides the immediate trauma) is cerebral oedema, which elevates intracranial pressure, and can result in cerebral ischaemia [3]; as such, intracranial hypertension is a medical emergency. As increases in intracranial pressure (ICP) are inversely proportional to survival [4], treatment aims to reduce ICP
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