The Laboratory Characterization of Fugitive Aerosol Emissions From a Standard Jet Nebulizer With and Without a Filtered Mouthpiece.

Background and objective The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from patients with coronavirus disease 2019 (COVID-19) during nebulization is unclear. In this study, we aimed to address this issue. Methods Fugitive emissions of aerosolized saline during nebulization were observed using a standard jet nebulizer fitted with unfiltered and filtered mouthpieces connected via a mannequin to a breathing simulator. Fugitive emissions were observed by using a laser sheet and captured on high-definition video, and they were measured by using optical particle counters positioned where a potential caregiver may be administering nebulization and three other locations in the sagittal plane at various distances downstream of the mannequin. Results The use of a standard unfiltered mouthpiece resulted in significant emission of fugitive aerosols ahead of and above the mannequin (spread over 2 m in front). A mouthpiece with a filter-adaptor effectively suppressed the emissions, with only minor leakage from the nebulizer cup. Particle count measurements supported the visual observations, providing total particle count levels and aerosol concentration levels at the measurement locations. The levels decayed slowly with downstream distance. Conclusions The visualization described above captured the dispersion of emitted aerosols in the plane of the laser sheet, aligned with the sagittal plane. The particle count measurements provided temporal and spatial distributions of the aerosol concentration levels over the time and locations considered. However, the exhaled air and aerosolized droplets spread three-dimensionally in front of and above the mannequin. The results visually highlight the effectiveness of using a filtered mouthpiece in suppressing the fugitive aerosols and identify an approach for limiting the occupational exposure of healthcare workers to these emissions while administering nebulized therapies.

Modifying matrix micro-environmental pH to achieve sustained drug release from highly laminating alginate matrices.

Lamination of alginate matrix tablet at acidic pH can compromise its function as a sustained release carrier. This phenomenon is associated with the conversion of sodium alginate to alginic acid. An innovative approach for controlling the release of a highly water-soluble drug from such matrices is presented in this paper. Inclusion of pH-modifiers was employed to raise the micro-environmental pH within matrices undergoing dissolution at gastric pH. The changes in micro-environmental pH of hydrating alginate matrices were visualized with the aid of a pH-indicator and subsequently quantified using image analysis. Transient elevation in micro-environmental pH impeded alginate protonation and minimized or prevented matrix lamination, contributing to preservation of drug diffusion barrier. Significant reduction in the rate of drug release at pH 1.2 was achieved in the presence of such additives. The action of pH-modifiers was synergistically enhanced in the presence of a carbon dioxide barrier formed by effervescing sodium bicarbonate, reducing drug release in the acidic medium from 60 to 20%. Further insight into the influence of lamination on drug release from alginate compacts was given.

Mechanistic study on hydration and drug release behavior of sodium alginate compacts.

The influence of sodium alginate viscosity on the dynamics of matrix hydration, solvent front movement, swelling, erosion, and drug release from alginate matrix tablets were examined. The solvent front showed preferential penetration from the radial direction even though matrix swelling showed axial predominance. This study proposed alternative views for the anisotropic behavior of hydrating alginate compacts, namely, formation of gel barrier with different permeability characteristics, tension at the gel-core interface and preferential radial erosion, in addition to an in-depth examination on the contribution of stress relaxation of hydrated polymer as well as core expansion. Alginate matrices demonstrated pH-dependent hydration, swelling and erosion behavior, resulting in pH-dependent drug release mechanisms. Dissolution profiles for alginate matrices of different viscosities were similar in acid but differed upon increase of pH. This was due to the influence of alginate viscosity grade on liquid uptake, erosion and pronounced swelling at near neutral pH.

Evaluation of sodium alginate as drug release modifier in matrix tablets.

Alginates are useful natural polymers suitable for use in the design of pharmaceutical dosage forms. However, the effects of particle size, viscosity and chemical composition of alginates on drug release from alginate matrix tablets are not clearly understood. Hence, 17 grades of sodium alginate with different particle size distributions, viscosities and chemical compositions were used to prepare matrix tablets at various concentrations to screen the factors influencing drug release from such matrices. Particle size was found to have an influence on drug release from these matrices. Sodium alginate was subsequently classified into several size fractions and also cryogenically milled to produce smaller particle size samples. Cryogenic milling could be successfully applied to pulverize coarse alginate particles without changing the quality through degradation or segregation. This study showed the significance of each alginate property in modulating drug release: particle size is important in initial alginic acid gel barrier formation as it affected the extent of burst release; higher alginate viscosity slowed down drug release rate in the buffer phase but enhanced release rate in the acid phase; high M-alginate might be more advantageous than high-G-alginate in sustaining drug release; and, the effect of increasing alginate concentration was greater with larger alginate particles. This can serve as a framework for formulators working with alginates. Furthermore, the results showed that sodium alginate matrices can sustain drug release for at least 8 h, even for a highly water-soluble drug in the presence of a water-soluble excipient.