Issue link: https://www.e-digitaleditions.com/i/1521797
14 June 2024 Inhalation tion products were prepared. After lyophilization, dried thin films were milled into a flowable pow- der and successfully filled into Aptar UDSp nasal spray systems using drum filling technology with no significant impacts on delivered dose or particle size distribution. Due to its unique and favorable processing conditions, the TFFD technology is a promising platform for the production of a wide range of powdered nasal products, including sensi- tive biologics and nucleic acid-based products such as mRNA-lipid nanoparticles (LNPs). In vitro characterization Nasal spray powders should be characterized and tested for both physical and biopharmaceutical properties [14, 27]. e physical characteristics include particle size, morphology and residual mois- ture, which determine flowability, aerodynamic pro- files and particle deposition patterns in the nasal cavity. Additionally, the biopharmaceutical charac- teristics include mucoadhesion, drug dissolution, permeation and solid-state form, which determine drug release, stability and bioavailability. In vitro characterization methods have been improved to assess nasal residence time and drug permeation. ese methods include the use of anatomically rel- evant testing tools like the Alberta Idealised Nasal Inlet (AINI) (Copley Scientific, Nottingham, UK) for deposition studies, powder dissolution in phys- iologically relevant media to determine drug release profiles and nasal epithelial cell models for evaluat- ing drug permeability [28]. When evaluating excip- ients and their effectiveness for mucoadhesion at prolonging residence time, investigators have com- bined a novel agar-mucin coated plate method with which consisted of a protein antigen, an adjuvant carried by liposomes, and a mucoadhesive agent, exhibited desirable aerosol properties for intranasal delivery, without negatively impacting the integ- rity of the antigen and adjuvant after TFFD pro- cessing. According to the investigation, the TFFD vaccine powders can be effectively delivered to the desired areas in the nasal cavity, particularly in the region where nasal-associated lymphatic tissues are located, by using Aptar Pharma's Unidose powder (UDSp) nasal spray device (Aptar Pharma, Louveci- ennes, France). is was demonstrated by testing on 3D-printed nasal casts based on computed tomogra- phy (CT) scans of the noses of both adults and chil- dren. Figure 2 illustrates the deposition patterns of the TFFD vaccine powder in the nasal cast based on a 48-year-old adult, demonstrating that the majority of vaccine was delivered into the middle turbinate, lower turbinate and nasopharynx regions, after the powder was actuated from the device to the nasal cast. ese powders, without any pre-conditioning, were manually filled into the devices. However, this does not accurately represent the handling of TFFD material in industrial settings. To enable the fill- ing operation, the TFFD thin films would need to be transformed into flowable powders with suitable bulk properties for dosing on automated encapsula- tion/cartridge filling equipment. A recent study (Sandoval, Jara, Williams, Watts and Cui; unpublished data) was conducted to assess the formulation and processing strategies to improve the bulk flow and handling properties of a TFFD dry powder of mAb. Prior to thin film freezing, aqueous dispersions containing mAb formulation and excipients previously used in approved inhala- Figure 2 Nasal deposition pattern of a thin-film freeze-dried (TFFD) vaccine powder in a 3D-printed nasal cast, based on the computed tomography (CT) scan of the nose of a 48-year-old male (0° coronal angle, 45° sagittal angle, 10 liters per min flow rate). 0 5 10 15 20 25 30 35 40 45 50 55 3D-printed nasal cast 1 2 3 4 5 6 Deposition pattern of a TFFD vaccine powder in a nasal cast 1) Vestibule 2) Upper turbinate 3) Middle turbinate 4) Lower turbinate 5) Nasopharnyx 6) Filter % Deposited