In Vitro Comparison of Local Nasal Vaccine Delivery and Correlation with Device Spray Performance.

PURPOSE: This study is the first vaccine candidate in vitro investigation with a focus on finding a correlation between the spray characteristics and the delivery efficiency of the local deposition in the nasal airways of infants under 24 months using various intranasal devices. METHODS: In vitro tests were developed to measure the spray characteristics of four intranasal delivery devices and how they regionally deliver a candidate vaccine formulation matrix in five nasal airway replicas (3 to 24 months). The correlation between the spray performance, geometric parameters, and delivery efficiency were assessed. RESULTS: All four devices performed consistently in terms of spray characteristics and were capable of delivering a high percentage of the candidate vaccine to the target areas, with a minimum delivery efficiency of 80%. Moreover, the delivery efficiency was affected by either the spray droplet size distribution or the distance between the nozzle tip and the internal nasal valve. Correlations between the spray performance and the in vitro local dose deposition were established. CONCLUSION: The infant nasal model tests can be complementary to device spray performance evaluation. In the absence of in vivo correlations, they can also facilitate the process of new product development by estimating delivery a priori.

Further Step toward a Comprehensive Understanding of the Effect of Surfactant Additions on Altering the Impact Dynamics of Water Droplets.

The addition of surfactants to pure water for specific applications has made controlling the impact dynamics of surfactant-laden droplets a complex phenomenon. This work investigates the influence of the molecular weight (MW), concentration, and ionic nature of the surfactants as well as the substrate surface characteristics on the impact dynamics of surfactant-laden droplets using a high-speed camera at 10 000 frames per second. Sodium dodecyl sulfate, hexadecyltrimethylammonium bromide, and n-decanoyl-n-methylglucamine were used as anionic, cationic, and nonionic surfactants, respectively. We used hydrophilic glass slides, hydrophobic polytetrafluoroethylene, and superhydrophobic alkyl ketene dimer (AKD) as substrates. The results show that the efficiency of the surfactant addition in increasing the maximum spreading diameter is significantly influenced by the molecular weight and ionic nature of the solutions as well as the nonwettability of the substrate. Among all of the surfaces examined, the concentration and ionic nature of the solutions were found to be more dominant parameters in determining the energy dissipation in the retraction phase of the droplet impact on the superhydrophobic AKD surfaces. As the concentration decreases or positive charges are present in the solution, it is more likely to observe a similar retraction dynamic to pure water when the droplet hits the superhydrophobic AKD having negatively charged surface sites. Finally, in terms of the impact outcomes of the surfactant-laden droplets on the superhydrophobic AKD, it is shown that the influence of the surfactant addition is more noticeable at lower Weber numbers, where the droplet tries to rebound by overcoming the energy loss that occurred in the spreading.

Impact Dynamics and Freezing Behavior of Surfactant-Laden Droplets on Non-Wettable Coatings at Subzero Temperatures.

The present study investigates the impact and freezing behavior of the droplets of surfactant solutions on non-wettable coatings at very low temperatures of -10 to -30 °C. Our goal is to elucidate the critical role of concentration, molecular weight, and ionic nature of surfactants on these phenomena. To achieve this goal, we used sodium dodecyl sulfate (anionic), hexadecyltrimethylammonium bromide (cationic), and n-decanoyl-n-methylglucamine (nonionic) at four concentrations ranging from 0 to 2 × CMC (critical micelle concentration). We captured the impact-freezing of the droplets on superhydrophobic alkyl ketene dimer coatings using a high-speed camera at 5000 frames per second. The results show that the ability of the droplets to spread and retract on the coatings is a function of concentration, ionic nature, and molecular weight of the surfactants, as well as the temperature-dependent viscosity of the solutions. Additionally, surfactant-laden droplets generally demonstrated an accelerated freezing compared to pure water. This might be due to the fact that the presence of surfactants can promote both heterogeneous ice nucleation from within the liquid and a larger solid-liquid interfacial area by filling the air pockets of the surface, leading to enhanced heat transfer. The behavior of the cationic surfactant at certain concentrations was, however, an exception leading to a freezing delay, for which a mechanism will be proposed.

Anatomically realistic nasal replicas capturing the range of nasal spray drug delivery in adults.

To improve the relationships between commonly conducted in vitro studies for locally-acting nasal spray drug products with in vivo regional deposition, this study developed a set of in vitro adult nasal geometries that captured the range of nasal drug delivery to the region posterior to internal nasal valve (INV), also known as posterior delivery (PD), and evaluated their performance with existing in vivo data. The PD of fluticasone propionate (FP) and fluticasone furoate (FF) in 40 nasal cavities was statistically analyzed to identify three airway models representing the low, mean, and high PD in adults. The models were also externally validated by comparing the in vitro nasal deposition from a different drug product (mometasone furoate (MF)) with the relevant in vivo data. The three selected geometries represented the low, mean, and high PD with multiple nasal sprays. They were verified in terms of reproducibility of in vitro data and validated by showing a reasonable agreement with preexisting in vivo MF PD despite differences in administration and defining the regions. The three models are envisioned to potentially facilitate the development of locally-acting nasal sprays and provide a better understanding of how in vitro metrics relate to in vivo regional nasal deposition.

In vitro evaluation of regional nasal drug delivery using multiple anatomical nasal replicas of adult human subjects and two nasal sprays.

Quantifying drug delivery to the site of action using locally-acting nasal suspension sprays is a challenging but important step toward understanding bioequivalence (BE) between test and reference products. The main objective of this study was to investigate the in vitro deposition pattern of two common but different locally-acting nasal suspension sprays using multiple nasal cavities. Twenty anatomically accurate nasal replicas were developed from high-resolution sinonasal computed tomography scans of adults with healthy nasal airways. The airways were segmented into two regions of anterior and posterior to the internal nasal valve. Both sides of the septum were considered separately; hence, 40 nasal cavities were studied. The positioning of the spray nozzle in all 40 cavities was characterized by the head angle, coronal angle, and the insertion depth. Despite using a controlled protocol to minimize the anterior losses, a wide range of variability in posterior drug delivery was observed. The observed intersubject variability using this in vitro method may have important implications for understanding BE of locally-acting nasal suspension sprays.

A facile, fast, and low-cost method for fabrication of micro/nano-textured superhydrophobic surfaces.

HYPOTHESIS: Alkyl ketene dimer (AKD) is frequently used in paper industry as an inexpensive sizing agent. The formation of a porous structure after curing the solidified AKD for an extra-long time (4-6 days) results in superhydrophobicity. In this study, a facile and low-cost method was utilized to turn the surface of AKD superhydrophobic in a very short period of time. EXPERIMENTS: We fabricated superhydrophobic coatings by dipping glass and paper substrates in molten AKD and then treating them with ethanol after solidification. The samples were characterized by X-ray diffraction, Scanning electron microscopy, Fourier transform-infrared spectroscopy, X-ray photoelectron spectroscopy, Confocal laser scanning microscopy, and dynamic contact angle goniometry. FINDINGS: The results show that briefly treating the coatings, obtained from isothermally heated AKD melt at 40 °C for 3 min, with ethanol leads to superhydrophobicity with advancing and receding contact angles of 158.7 ± 1.4° and 156.8 ± 0.9°, respectively. By increasing the melt temperature to 70 °C and its heating time to 6 h followed by ethanol treatment, the advancing and receding contact angles increased to 163.7 ± 1.3° and 162.6 ± 1.2°, respectively. This enhancement in superhydrophobicity is due to the formation of porous, entangled irregular micro/nano textures that create air cushions on the surface resulting in droplet state transition from Wenzel to Cassie.