Characterization of Spray-Dried Powders Using a Coated Alberta Idealized Nasal Inlet.

Dry powders offer the potential to increase stability and reduce cold-chain requirements associated with the distribution of vaccines and other thermally sensitive products. The Alberta Idealized Nasal Inlet (AINI) is a representative geometry for characterization of nasal products that may prove useful in examining intranasal delivery of powders. Spray-dried trehalose powders were loaded at 10, 20, and 40 mg doses into active single-dose devices.

Characterizing regional drug delivery within the nasal airways.

Introduction: The nose has been receiving increased attention as a route for drug delivery. As the site of deposition constitutes the first point of contact of the body with the drug, characterization of the regional deposition of intranasally delivered droplets or particles is paramount to formulation and device design of new products.

Areas Covered: This review article summarizes the recent literature on intranasal regional drug deposition evaluated in vivo, in vitro and in silico, with the aim of correlating parameters measured in vitro with formulation and device performance.

High-Flow and Low-Flow Oxygen Delivery by Nasal Cannula Evaluated in Infant and Adult Airway Replicas.

Background: The nasal cannula is widely regarded as a safe and effective means of administering low- and high-flow oxygen to patients irrespective of their age. However, variability in delivered oxygen concentration (F F ) via nasal cannula has the potential to pose health risks. The present study aimed to evaluate predictive equations for F over a large parameter space, including variation in breathing, oxygen flow, and upper-airway geometry representative of both young children and adults.

Size-specific filtration efficiency and pressure drop of school-aged children's woven and nonwoven masks at varying face velocities.

Background: Differences in physiology and breathing patterns between children and adults lead to disparate responses to aerosols of varying sizes. No standardized method exists for measuring the filtration efficiency (FE) of children's masks to reflect such differences.

Methods: Using an adult N95 mask as a control and two different face velocities (v) (9.

Variability in low-flow oxygen delivery by nasal cannula evaluated in neonatal and infant airway replicas.

Background: The nasal cannula is considered a trusted and effective means of administering low-flow oxygen and is widely used for neonates and infants requiring oxygen therapy, despite an understanding that oxygen concentrations delivered to patients are variable.

Methods: In the present study, realistic nasal airway replicas derived from medical scans of children less than 3 months old were used to measure the fraction of oxygen inhaled (FiO) through nasal cannulas during low-flow oxygen delivery. Parameters influencing variability in FiO were evaluated, as was the hypothesis that measured FiO values could be predicted using a simple, flow-weighted calculation that assumes ideal mixing of oxygen with entrained room air.

Using Filters to Estimate Regional Lung Deposition with Pressurized Metered Dose Inhalers.

Purpose: To evaluate the suitability of a recently proposed apparatus that uses filters to directly fractionate the in vitro lung dose into regional deposition estimates for use with pressurized metered dose inhaler (pMDI) devices as a less resource intensive alternative to cascade impaction.

Methods: Using three commercially available pMDI devices (Asmanex HFA, Ventolin HFA, QVAR), regional deposition estimates were measured directly using the filter-based apparatus (FBA). Regional deposition estimates were also generated for the same inhalers by performing cascade impaction measurements and inputting the results to an in silico regional deposition model.

In Vitro Regional Deposition of Nasal Sprays in an Idealized Nasal Inlet: Comparison with In Vivo Gamma Scintigraphy.

Purpose: To compare in vitro regional nasal deposition measurements using an idealized nasal airway geometry, the Alberta Idealized Nasal Inlet (AINI), with in vivo regional deposition for nasal drug products.

Materials And Methods: One aqueous solution formulation (NasalCrom), one aqueous suspension formulation (Nasonex) and one nasal pressurized metered dose spray device (QNASL) were selected. Two spray orientation angles, 60° and 45° from the horizontal, were selected.

Intranasal delivery of a synthetic Entamoeba histolytica vaccine containing adjuvant (LecA + GLA-3 M-052 liposomes): In vitro characterization.

Amebiasis, a disease caused by the parasite Entamoeba histolytica, is estimated to cause millions of infections and at least 55,000 deaths globally each year. With no vaccine currently available, there is an urgent need for an accessible means of stimulating protective mucosal immunity. The objective of this study was to characterize the nasal spray of a novel amebiasis vaccine candidate from a syringe-based liquid atomization device, the Teleflex MAD Nasal™, in both adult and infant nasal airways.

Characterization of dry powder inhaler performance through experimental methods.

Experimental methods provide means for the quality control of existing DPIs and for exploring the influence of formulation and device parameters well in advance of clinical trials for novel devices and formulations. In this review, we examine the state of the art of in vitro testing of DPIs, with a focus primarily on the development of accurate in vitro-in vivo correlations. Aspects of compendial testing are discussed, followed by the influence of flow profiles on DPI performance, the characterization of extrathoracic deposition using mouth-throat geometries, and the characterization of regional thoracic deposition.

Self-determination and co-operation in supported mealtimes involving people with severe intellectual disabilities.

Purpose: People with severe intellectual disabilities are often supported during mealtimes. However, little information exists about how they and care staff co-ordinate their mealtime behaviours.

Method: Four people with severe intellectual disabilities and 12 members of care staff participated in this research.

Empirical Deposition Correlations.

Traditionally, empirical correlations for predicting respiratory tract deposition of inhaled aerosols have been developed using limited available data. More recently, advances in medical image segmentation and additive manufacturing processes have allowed researchers to conduct extensive deposition experiments in realistic replicas of the upper and central branching airways. This work has led to a collection of empirical equations for predicting regional aerosol deposition, especially in the upper, nasal and oral airways.

Spray Dried Rugose Lipid Particle Platform for Respiratory Drug Delivery.

Purpose: To develop a new lipid-based particle formulation platform for respiratory drug delivery applications. To find processing conditions for high surface rugosity and manufacturability. To assess the applicability of the new formulation method to different lipids.

Use of Airway Replicas in Lung Delivery Applications.

The use of extrathoracic airway replicas in optimization of drug delivery to the lungs with nebulizers, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs) is discussed. Such airway replicas have been useful in evaluating new pulmonary drug delivery platforms mainly based on the comparison of the total lung dose (TLD) and the aerodynamic particle size distribution (APSD) of the aerosol distal to the physical models. The ability of these methods to replicate results has allowed advancements in respiratory drug delivery and in the accuracy and utility of - correlations (IVIVCs).

Polyreactivity and polyspecificity in therapeutic antibody development: risk factors for failure in preclinical and clinical development campaigns.

Antibody-based drugs, which now represent the dominant biologic therapeutic modality, are used to modulate disparate signaling pathways across diverse disease indications. One fundamental premise that has driven this therapeutic antibody revolution is the belief that each monoclonal antibody exhibits exquisitely specific binding to a single-drug target. Herein, we review emerging evidence in antibody off-target binding and relate current key findings to the risk of failure in therapeutic development.

Comparison of airway pressures and expired gas washout for nasal high flow versus CPAP in child airway replicas.

Background: For children and adults, the standard treatment for obstructive sleep apnea is the delivery of continuous positive airway pressure (CPAP). Though effective, CPAP masks can be uncomfortable to patients, contributing to adherence concerns. Recently, nasal high flow (NHF) therapy has been investigated as an alternative, especially in CPAP-intolerant children.

Using Filters to Estimate Regional Lung Deposition with Dry Powder Inhalers.

Purpose: To develop an in vitro method to rapidly evaluate regional lung doses delivered by pharmaceutical inhalers. Currently, cascade impactor measurements are used, but these are resource intensive and require significant post processing of in vitro data to arrive at regional deposition estimates.

Methods: We present a specialized filter apparatus that mimics tracheobronchial (TB) deposition of pharmaceutical aerosols emitted by commercially available dry powder inhalers (DPIs).

Size-Specific Filtration Performance of N95 Respirators After Decontamination by Moist Heat Incubation.

Decontamination and reuse of respirators have been proposed to mitigate the shortage of respirators during pandemics. The U.S.

Deposition of Aerosols in the Lungs: Particle Characteristics.

Of the various particle properties that affect deposition in the respiratory tract, particle diameter and particle density are the most commonly considered, since their effect on deposition is well known and important, as has been discussed earlier in this chapter. However, there are several other particle properties that can affect particle deposition in the lungs. These include: 1) electrostatic charge on the particle, which can cause electrostatic forces to enhance deposition; 2) the shape of the particle, which can cause its trajectory to differ from that of a spherical particle and thereby alter its deposition; and 3) volatility of the particle i.

Trileucine as a dispersibility enhancer of spray-dried inhalable microparticles.

The formation of trileucine-containing spray-dried microparticles intended for pulmonary delivery was studied in depth. A single-particle method was employed to study the shell formation characteristics of trileucine in the presence of trehalose as a glass former, and an empirical correlation was proposed to predict the instance of shell formation. A droplet chain instrument was used to produce and collect monodisperse particles to examine morphology and calculate particle density for different levels of trileucine.

A simple HEPA filtering facepiece.

Shortages of efficient filtering facepiece respirators leave the public vulnerable to transmission of infectious diseases in small particle aerosols. This study demonstrates that a high-filtration-efficiency facepiece capable of filtering out >95% of 0.05μm particles while being worn can be simply produced with available materials.

Forms of resistance in people with severe and profound intellectual disabilities.

Government policy in the UK emphasises that people with intellectual disabilities should have the opportunity to make choices and exert control over their own lives as much as possible. The ability of a person to resist activities and offers is therefore important, particularly for people with severe and profound intellectual disabilities, who are likely to have language impairments and need to communicate their choices non-verbally. Video and ethnographic data were collected from two services for people with severe and profound intellectual disabilities.

On the particle formation of leucine in spray drying of inhalable microparticles.

The particle formation of L-leucine, a dispersibility-enhancing amino acid used in the spray drying of inhalable pharmaceutical aerosols, was extensively studied using three experimental methods, and the results were interpreted with the aid of theory. A comparative-kinetics electrodynamic balance was used to study the shell formation behavior in single evaporating microdroplets containing leucine and trehalose. Different concentration thresholds of solidification and shell formation were determined for trehalose and leucine, which were then used in the particle formation model to predict the properties of spray-dried particles.