Journal
JOURNAL OF CONTROLLED RELEASE
Volume 237, Issue -, Pages 147-159Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.07.001
Keywords
Intranasal; Nose-to-brain; Benzodiazepines; Seizure emergencies; Diazepam; Nasal delivery device; Epilepsy
Funding
- Academic Health Center, University of Minnesota
- American Epilepsy Society
- Epilepsy Foundation
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Epileptic seizure emergencies are life-threatening conditions, which in their most severe form, status epilepticus, have a high mortality rate if not quickly terminated. Treatment requires rapid delivery of anti-epileptics such as benzodiazepines to the brain. The nasal route is attractive due to its non-invasiveness, potential for direct nose to brain delivery, high vascularity, relatively large absorptive surface area, and avoidance of intestinal/livermetabolism. However, the limited volume of the nasal cavity and poor water solubility of anti-epileptics restrict absorption, leading to insufficient therapeutic brain levels. This review covers various formulation approaches adopted to improve nasal delivery of drugs, especially benzodiazepines, used to treat seizure emergencies. Other general topics such as nasal anatomy, challenges to nasal delivery, and drug/formulation considerations for nose to brain delivery are also discussed. (C) 2016 Elsevier B.V. All rights reserved.
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