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Targeting the Upper Nasal Space: A Novel, Efficient Route for Systemic Drug Delivery

Shrewsbury SB, Ray S, Fuller C, Hoekman J.

Respiratory Drug Delivery 2021. Volume , 2021: 117-126.

Abstract:

The Precision Olfactory Delivery (POD®) system was developed to specifically deliver drugs to the upper nasal space to take advantage of rapid absorption by the highly vascular bed underlying the olfactory mucosa. The POD is a customizable platform that can be engineered to a specific drug and formulation and has been used for intranasal delivery of dihydroergotamine (DHE: liquid formulation) for migraine and olanzapine (OLZ: spray dried powder formulation) for agitation. Clinical development programs for DHE (INP104) and OLZ (INP105) are described. INP104 was well tolerated and demonstrated a comparable PK profile to intravenous DHE from 30 minutes to 48 hours (except for a lower peak concentration) and a faster Tmax, four-fold greater Cmax and three-fold greater AUC compared to Migranal nasal spray pump, despite <75% of the same formulation being delivered. Because the POD targets the upper nasal space, extensive safety studies including assessment of olfactory mucosa function, mucosal integrity, inflammation and irritation were undertaken. Another program delivering OLZ powder (INP105) demonstrated rapid absorption of OLZ and pharmacodynamic effects in healthy volunteers.

Both DHE and OLZ clinical development programs show the feasibility of targeting the upper nasal space as a potential route of administration for drugs where rapid onset of action is desirable.