Issue link: https://www.e-digitaleditions.com/i/1521797
Inhalation June 2024 11 erence 13 indicates that the nasal sprays can achieve a median time to maximum concentration (T max ) ranging from 2.5 to 30 minutes—comparable to tra- ditional epinephrine autoinjectors. Formulation and characterization approach Formulation considerations e nasal mucosa is an excellent site for systemic absorption with approximately 150 cm 2 available for deposition. It is generally accepted that the nasal route will accommodate between 10 and 25 mg of powder in a single dose [14]. e formulation approach should enable these products by stabilizing the active pharmaceutical ingredient (API) and pre- senting it to the nasal mucosal in a way that will facil- itate bioavailability and quick onset-of-action. Rapid absorption is necessary since mucociliary clearance will move mucus and deposited powder toward the nasopharynx at a rate of approximately 6 mm/min. Mucoadhesive and viscosity-enhancing polymers can be included in the powder formulation to effectively hydroxypropyl methylcellulose (HPMC) to create a physical barrier to the mucosal layer where a virus may infect and replicate. During the COVID-19 pandemic, several products composed predominantly of HPMC powder were approved in the EU and Asia [9] as medical devices (having no chemically active ingredient) for nasal administration to reduce viral infection. Once deposited in the nasal cavity, these cellulose powders swell to create an additional bar- rier to the mucosal surface and, when combined with appropriate buffer salts, can create a mildly acidic pH that is hostile towards many viruses [10, 11]. Emergency anaphylaxis treatment Nasal powders are currently being explored as a potential solution to address the limitations of autoinjector- based anaphylaxis treatments, specifi- cally around injection fears, misuse and short shelf life [12]. Recent research has demonstrated promis- ing pharmacokinetic and pharmacodynamic results for nasal epinephrine products. ese studies have found that nasal sprays can achieve pharmacokinetic results similar to traditional intramuscular epineph- rine autoinjectors [13]. Specifically, the review in ref- Figure 1 A schematic representation of the nasal spray drug delivery process. The process begins with manufacturing of the powder, using techniques such as spray drying, as shown at the left of the diagram. During manufacturing (top center), control over moisture and glass transition temperature (Tg) should be maintained to avoid instability such as particle fusing (as shown in the scanning electron micrographs, SEMs). After the powder is manufactured, it is filled into the spray devices. Devices are actuated into the nasal cavity (bottom right). Mucosal deposition and subsequent dissolution (bottom center and left) occur where the opportunity for absorption is limited by the rate of mucociliary clearance. Abbreviations: TFFD = thin-film freeze drying; Tg = glass transition temperature; RH = relative humidity; MCC = mucociliary clearance. Powder manufacturing Formulation strategy for vitrification • Spray drying • Micronization • TFFD Drug dissolution Removed from nasal cavity by MCC Clearance slowed by excipients Glass transition temperature (Tg) Low RD production/packaging, hydrophobic shell formers Water content Nasal spray device filling Powder deposition profile Nasal spray Drug To the nasopharynx Mucus Ciliated cells Systemic circulation Time