Repurposing excipients as active inhalation agents: The mannitol story
The story of how we came to use inhaled mannitol to diagnose asthma and to treat cystic fibrosis began when we were looking for a surrogate for exercise as a stimulus to identify asthma. We hadproposed that exercise-induced asthma was caused by an increase in osmolarity of the periciliary fluid. We found hypertonic saline to be a surrogate for exercise but an ultrasonic nebuliser wasrequired. We produced a dry powder of sodium chloride but it proved unstable. We developed a spray dried preparation of mannitol and found that bronchial responsiveness to inhaling mannitolidentified people with currently active asthma. We reasoned that mannitol had potential to replace the ‘osmotic’ benefits of exercise and could be used as a treatment to enhance mucociliary clearancein patients with cystic fibrosis. These discoveries were the start of a journey to develop several registered products that are in clinical use globally today.