Comparison of efficacies of full and abbreviated cascade impactors in aerosol characterization of nebulized salbutamol sulfate produced by a jet nebulizer

The properties of aerosols generated from salbutamol sulfate solution (1 mg/mL) using an air-jet nebulizer were evaluated using Next Generation Impactor (NGI), a full cascade impactor, and Fast Screening Impactor (FSI), an abbreviated impactor measurement (AIM). Both impactors were operated under the same experimental conditions. The samples were recovered and assayed using validated high performance liquid chromatography (HPLC). The study investigated AIM-Human Respiratory Tract (HRT) concept by comparing key parameters of aerosolization i.e. fine particle dose (FPD) and fine particle fraction (FPF) measured using FSI, with NGI as baseline. The results showed that FSI yielded different but comparable values for FPD and FPF, indicating that it is alternative impactor to NGI. Despite the fact that FSI could not replace NGI, it may be used as an alternative impactor for simple and rapid aerosol characterization of formulations in some pharmaceutical development and quality control processes.

Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target cystic fibrosis (CF)-common pathogens, were aerosolized by jet nebulizer and administered to a real-scale computed tomography (CT)-derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.

Particle Dynamics and Bioaerosol Viability of Aerosolized BCG Vaccine Using Jet and Vibrating Mesh Clinical Nebulizers

BackgroundBacillus Calmette–Guérin (BCG) is a vaccine used to protect against tuberculosis primarily in infants to stop early infection in areas of the world where the disease is endemic. Normally administered as a percutaneous injection, BCG is a live, significantly attenuated bacteria that is now being investigated for its potential within an inhalable vaccine formulation. This work investigates the feasibility and performance of four jet and ultrasonic nebulizers aerosolizing BCG and the resulting particle characteristics and residual viability of the bacteria post-aerosolization.MethodsA jet nebulizer (Collison) outfitted either with a 3- or 6-jet head, was compared to two clinical nebulizers, the vibrating mesh Omron MicroAir and Aerogen Solo devices. Particle characteristics, including aerodynamic particle sizing, was performed on all devices within a common aerosol chamber configuration and comparable BCG innocula concentrations. Integrated aerosol samples were collected for each generator and assayed for bacterial viability using conventional microbiological technique.Results and ConclusionsA batch lot of BCG (Danish) was grown to titer and used in all generator assessments. Aerosol particles within the respirable range were generated from all nebulizers at four different concentrations of BCG. The jet nebulizers produced a uniformly smaller particle size than the ultrasonic devices, although particle concentrations by mass were similar across all devices tested with the exception of the Aerogen Solo, which resulted in a very low concentration of BCG aerosols. The resulting measured viable BCG aerosol concentration fraction produced by each device approximated one another; however, a measurable decrease of efficiency and overall viability reduction in the jet nebulizer was observed in higher BCG inoculum starting concentrations, whereas the vibrating mesh nebulizer returned a remarkably stable viable aerosol fraction irrespective of inoculum concentration.

Effects of distancing and pattern of breathing on the filtering capability of commercial and custom-made facial masks: An in-vitro study

Background Since the beginning of the COVID-19 pandemics, masking policies have been advocated. While masks are known to prevent transmission towards other individuals, it is unclear if different types of facial masks can protect the user from inhalation. The present study compares in-vitro different commercial and custom-made facial masks at different distances and breathing patterns. Methods Masks were placed on a head mannequin connected to a lung simulator, using a collecting filter placed after the mannequin airway. Certified, commercial and custom-made masks were tested at three different distances between the emitter and the mannequin: 40 cm, 80 cm and 120 cm. Two patterns of breathing were used, simulating normal and polypneic respiration. A solution of methylene blue was nebulized with a jet nebulizer and different mask-distance-breathing pattern combinations were tested. The primary endpoint was the inhaled fraction, defined as the amount of methylene blue detected with spectrophotometry expressed as percent of the amount detected in a reference condition of zero distance and no mask. Findings We observed a significant effect of distance (p < 0.001), pattern of breathing (p = 0.040) and type of mask (p < 0.001) on inhaled fraction. All masks resulted in lower inhaled fraction compared to breathing without mask (p < 0.001 in all comparisons), ranging from 41.1% ± 0.3% obtained with a cotton mask at 40 cm distance with polypneic pattern to <1% for certified FFP3 and the combination of FFP2 + surgical mask at all distances and both breathing pattern conditions. Discussion Distance, type of device and breathing pattern resulted in highly variable inhaled fraction. While the use of all types of masks resulted relevantly less inhalation compared to distancing alone, only high-grade certified devices (FFP3 and the combination of FFP2 + surgical mask) ensured negligible inhaled fraction in all conditions.

An Automated Jet Nebulizer with Dynamic Flow Regulation

PurposeThe present study is focused on designing an automated jet nebulizer that possesses the capability of dynamic flow regulation. In the case of existing equipment, a high fraction of the aerosol is lost to the atmosphere through the vent, during the exhalation phase of respiration. Specifically, 50% of the volume of aerosol generated, is wasted. Desired effects of nebulization may not achieve by neglecting this poor administration technique. There may be adverse effects like bronchospasm, and exposure to high drug concentrations.MethodsThe proposed nebulizer is composed of two modes as “Compressed Air” mode and “Oxygen Therapy” mode. The automated triggering from one mode to another will be dependent upon the percentage of oxygen saturation of the patient, monitored from the SpO2 sensor. The compressed airflow will be delivered to the patient according to his or her minute ventilation, derived with the aid of a temperature sensor-based algorithm.ResultsThe compressor circuitry controller ensures that the patient receives compressed air as per the flow rate decided by the system. At the end of the drug delivery, if the liquid level sensor detects the absence of medication within the nebulizer chamber, the nebulization process will be terminated.ConclusionsThe dynamic regulation of the motor speed with respect to the minute ventilation was accomplished successfully. A laminar flow was obtained from the outlet of the compressor towards the nebulizer tubing, and a turbulent flow was obtained within the chamber, as expected. No excessive turbulent flows or rotational flow patterns were detected. The result could certainly lead to the improvements of the existing nebulizers.