Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

Abstract

The nose offers an attractive noninvasive alternative for drug delivery. Nasal anatomy, with a large mucosal surface area and high vascularity, allows for rapid systemic absorption and other potential benefits. However, the complex nasal geometry, including the narrow anterior valve, poses a serious challenge to efficient drug delivery. This barrier, plus the inherent limitations of traditional nasal delivery mechanisms, has precluded achievement of the full potential of nasal delivery. Breath Powered bi-directional delivery, a simple but novel nasal delivery mechanism, overcomes these barriers. This innovative mechanism has now been applied to the delivery of sumatriptan. Multiple studies of drug deposition, including comparisons of traditional nasal sprays to Breath Powered delivery, demonstrate significantly improved deposition to superior and posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies in both healthy subjects and migraineurs suggest that improved deposition of sumatriptan translates into improved absorption and pharmacokinetics. Importantly, the absorption profile is shifted toward a more pronounced early peak, representing nasal absorption, with a reduced late peak, representing predominantly gastrointestinal (GI) absorption. The flattening and “spreading out” of the GI peak appears more pronounced in migraine sufferers than healthy volunteers, likely reflecting impaired GI absorption described in migraineurs. In replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was well accepted and well tolerated by patients, and onset of pain relief was faster than generally reported in previous trials with noninjectable triptans. Interestingly, Breath Powered delivery also allows for the potential of headache-targeted medications to be better delivered to the trigeminal nerve and the sphenopalatine ganglion, potentially improving treatment of various types of headache. In brief, Breath Powered bi-directional intranasal delivery offers a new and more efficient mechanism for nasal drug delivery, providing an attractive option for improved treatment of headaches by enabling or enhancing the benefits of current and future headache therapies.

The Nasal Approach to Delivering Treatment for Brain Diseases: An Anatomic, Physiologic, and Delivery Technology Overview

“…The target sites for N2B delivery are located in the upperconvoluted slit-like nasal passages beyond this narrow anterior nasal valve. Reproduced with permission from [132].…”

“…The Breath Powered delivery concept was developed to overcome the anatomical and physiological char- Reproduced with permission from [23,132].…”

“…Other studies comparing pharmacokinetics and migraine pain relief after delivery of sumatriptan with a Breath Powered pow-der device in comparison to liquid nasal spray and SC injection also suggest the possibility that the targeted deposition may enhance the effects in a manner that cannot be attributed to improved serum absorption of sumatriptan alone [125,127,129,132].…”

“…Initial regional gamma deposition and horizontal distribution 2 min after self-administration with conventional spray pump and Breath Powered™ Bi-Directional™ nasal powder device. Reproduced with permission from [48,132].…”

A Randomized, Double‐Blind, Placebo‐Controlled Study of Breath Powered Nasal Delivery of Sumatriptan Powder (AVP‐825) in the Treatment of Acute Migraine (The TARGET Study)

“…The swallowed portion of the dose is then subject to the same challenges of variable intestinal absorption associated with oral delivery. This “dual route” of absorption from standard liquid nasal‐spray delivery is shown in pharmacokinetic (PK) studies of sumatriptan . A small peak in plasma concentration is observed at ∼20 minutes post‐dose (nasal absorption), followed by a delayed peak at ∼90 minutes post‐dose (intestinal absorption).…”