Inhalation

© Copyright Inhalation catalent.com q & a industry trend: Examining the Emergence of Unit- & Bi-Dose Nasal Sprays andrew samuelsson, ph.d. Product Manager, Oral & Specialty Delivery Featured Experts: craig davies-cutting, ph.d. Director, Inhaled Products & Technologies tom clark Director, Commercial Operations, Inhalation Molecules that are limited by a slow onset of action, a suboptimal side-effect profile, or a complicated administration process, may be good candidates for adaptation to a unit- or bi-dose nasal delivery format. This is especially true for drugs targeting the central nervous system (CNS). Established molecules may also benefit from shorter development timelines and regulatory review cycles. Nasal spray administration of medicine offers advantages over oral and intravenous (IV) delivery. Catalent's Andrew Samuelsson, Craig Davies- Cutting and Tom Clark discuss the advantages and opportunities of adopting unit- and bi-dose nasal delivery technology. samuelsson: Historically, nasal sprays have typically been associated with treatment of local conditions such as allergies/rhinitis. However, over the last 10+ years there has been an increasing focus on nasal administration for the delivery of molecules to the CNS as well as for systemic delivery. Dosing via the intranasal pathway has shown a rapid onset of action, comparable to that of IV administration, with kinetics considerably faster than that of oral delivery 1-3 . Intranasal administration has gained attention as a method to target the CNS since this route provides a practical, non-invasive means of bypassing the blood-brain barrier by leveraging the putative nose-to-brain pathway 4-7 . Relative to IV injection, intranasal delivery offers a similar onset of action, without the associated discomfort or need for administration by a healthcare professional. When targeting the CNS, intranasal delivery can achieve similar drug concentrations in the brain with a significantly lower concentration in circulation relative to IV 3,8 , thus likely reducing the prevalence and severity of systemic side-effects seen with high circulating drug concentrations. Unlike molecules transported via the nose-to-brain pathway, those that come from circulation often have difficulty breaching the blood- brain barrier, and it is estimated that 98% of small molecule drugs are unable to pass this barrier 9 . Techniques that forcibly bypass (e.g., intrathecal infusions) or weaken/open the blood-brain barrier (e.g., mannitol injection) can carry q: What are the advantages of the nasal route of administration? 4

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