Simultaneous delivery of dual drug ionic complex to brain by intranasal self-nano emulsifying drug delivery systems (SNEDDS) for treatment of brain disorders

As an emerging strategy for the treatment of brain disorders, targeting via intranasal delivery is strategically exploited for direct transport of therapeutic molecules to brain primarily via olfactory & trigeminal nerves for rapid onset of action & fast relief. However, due to limitation of dosage volume that can be delivered to the nasal cavity (about 50-200 µl per nostril per dose), the success is limited currently to highly potent drugs. Our ongoing work is to formulate a self-nano emulsifying drug delivery system (SNEDDS) based nasal spray technology capable of carrying higher payload of intranasal dosage, not for one, but for simultaneous delivery of two distinct therapeutic molecules as a single ionic drug complex. These dual drug complexes in the form of ionic liquids stabilized inside hydrophobic core of SNEDDS may enable the delivery of molecules solubilized in limited spray volumes for brain targeting by improving low solubility and/or permeability challenges of target molecules. Naproxen Sodium (BCS Class II; low solubility, high permeability) & Promethazine Hydrochloride (BCS Class III; high solubility, low permeability) were chosen as dual drugs for complexation to treat brain disorders such as migraine where the Promethazine-Naproxen complex can be delivered intranasally to bring about multi-symptom relief for severe headache and emesis.