Effect of crystallization kinetics on the properties of spray dried microparticles

<p>A droplet chain technique was used to study the influence of the crystallization process on the morphology of spray dried microparticles. A piezoceramic dispenser produced a chain of monodisperse solution droplets with an initial diameter in the range of 60–80 µm. Aqueous solutions of sodium nitrate were prepared in concentrations ranging from 5 mg/ml to 5⋅10⁻⁵ mg/ml. The solution droplets were injected into a laminar flow with gas temperatures varying from 25 to 150°C, affecting the droplet temperature and the evaporation rate, accordingly. Dried particles with diameters between 0.3 and 18 µm were collected. The properties of the collected microparticles were studied and correlated with a particle formation model which predicted the onset of saturation and crystallization. The model accounted for the dependence of the diffusion coefficient of sodium nitrate in water on droplet viscosity. The viscosity trend for sodium nitrate solutions was determined by studying the relaxation time observed during coalescence of two aqueous sodium nitrate droplets levitated in optical tweezers. The combination of theoretical derivations and experimental results showed that longer time available for crystallization correlates with larger crystal size and higher degrees of crystallinity in the final microparticles.</p> <p>© 2016 American Association for Aerosol Research</p

Development of a lyophilization process for Campylobacter bacteriophage storage and transport

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Bacteriophages are a sustainable alternative to control pathogenic bacteria in the post-antibiotic era. Despite promising reports, there are still obstacles to phage use, notably titer stability and transport‐associated expenses for applications in food and agriculture. In this study, we have developed a lyophilization approach to maintain phage titers, ensure efficacy and reduce transport costs of Campylobacter bacteriophages. Lyophilization methods were adopted with various excipients to enhance stabilization in combination with packaging options for international transport. Lyophilization of Eucampyvirinae CP30A using tryptone formed a cake that limited processing titer reduction to 0.35 ± 0.09 log10 PFU mL‐1. Transmission electron microscopy revealed the initial titer reduction was associated with capsid collapse of a subpopulation. Freeze‐dried phages were generally stable under refrigerated vacuum conditions and showed no significant titer changes over 3 months incubation at 4 °C (p = 0.29). Reduced stability was observed for lyophilized phages that were incubated either at 30 °C under vacuum or at 4 °C at 70% or 90% relative humidity. Refrigerated international transport and rehydration of the cake resulted in a total phage titer reduction of 0.81 ± 0.44 log10 PFU mL‐1. A significantly higher titer loss was observed for phages that were not refrigerated during transport (2.03 ± 0.32 log10 PFU mL‐1). We propose that lyophilization offers a convenient method to preserve and transport Campylobacter phages, with minimal titer reduction after the drying process

Pulmonary aerosol delivery and the importance of growth dynamics

Aerosols are dynamic systems, responding to variations in the surrounding environmental conditions by changing in size, composition and phase. Although, widely used in inhalation therapies, details of the processes occurring on aerosol generation and during inhalation have received little attention. Instead, research has focused on improvements to the formulation of the drug prior to aerosolization and the resulting clinical efficacy of the treatment. Here, we highlight the processes that occur during aerosol generation and inhalation, affecting aerosol disposition when deposited and, potentially, impacting total and regional doses. In particular, we examine the response of aerosol particles to the humid environment of the respiratory tract, considering both the capacity of particles to grow by absorbing moisture and the timescale for condensation to occur. [Formula: see text] </jats:p

Mechanistic modeling expedites the development of spray dried biologics

[EN] Spray drying can be used to extend the shelf life of biologics stored at ambient temperature. Empirical and statistical design of experiments approaches typically require a relatively large number of experiments to determine suitable formulation and spray drying process parameters. An alternative approach, which may require fewer experiments, is to use mechanistic models to select these parameters. In this paper, mechanistic models are applied to develop a bacteriophage powder expected to have long-term physical stability at ambient temperature. The developed powder may be useful for decreasing incidences of foodborne illness in Kenya.Carrigy, N.; Liang, L.; Wang, H.; Kariuki, S.; Nagel, T.; Connerton, I.; Vehring, R. (2018). Mechanistic modeling expedites the development of spray dried biologics. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1551-1558. https://doi.org/10.4995/IDS2018.2018.7472OCS1551155

Effect of storage temperature on the stability of spray dried bacteriophage powders

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2–0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106–107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.The University of Sydney; Australian Research Council; National Institute of Allergy and Infectious Diseases of the National Institutes of Health; National Health and Medical Research Council Centre of Research Excellence in Tuberculosis Contro

Enhanced Evaporation of Microscale Droplets With an Infrared Laser

Enhancement of water droplet evaporation by added infrared radiation was modeled and studied experimentally in a vertical laminar flow channel. Experiments were conducted on droplets with nominal initial diameters of 50 lm in air with relative humidities ranging from 0% to 90% RH. A 2800 nm laser was used with radiant flux densities as high as 4 Â 10 5 W/m 2 . Droplet size as a function of time was measured by a shadowgraph technique. The model assumed quasi-steady behavior, a low Biot number liquid phase, and constant gas-vapor phase material properties, while the experimental results were required for model validation and calibration. For radiant flux densities less than 10 4 W/m 2 , droplet evaporation rates remained essentially constant over their full evaporation, but at rates up to 10% higher than for the no radiation case. At higher radiant flux density, the surface-area change with time became progressively more nonlinear, indicating that the radiation had diminished effects on evaporation as the size of the droplets decreased. The drying time for a 50 lm water droplet was an order of magnitude faster when comparing the 10 6 W/m 2 case to the no radiation case. The model was used to estimate the droplet temperature. Between 10 4 and 5 Â 10 5 W/m 2 , the droplet temperature changed from being below to above the environment temperature. Thus, the direction of conduction between the droplet and the environment also changed. The proposed model was able to predict the changing evaporation rates for droplets exposed to radiation for ambient conditions varying from dry air to 90% relative humidity