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Spray-dried powders for inhalation

Su, Jiapei LU and Zhu, Qianru LU (2025) KLGM06 20251
Food Technology and Nutrition (M.Sc.)
Abstract
The pulmonary route has emerged as a promising strategy for delivering protein therapeutics, particularly for patients suffering from respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary infections.

This project investigated the effect of operating parameters of a laboratory spray dryer on the characteristics of powders composed of Bovine Serum Albumin (BSA), L-leucine, and Trehalose Dihydrate, with the aim of optimizing their production for inhalation applications. The pre-study focused on optimizing spray-drying process parameters, including feed concentration (solid content), inlet temperature, nozzle diameter, spray gas flow rate, and feed solution flow rate. The main study used the... (More)
The pulmonary route has emerged as a promising strategy for delivering protein therapeutics, particularly for patients suffering from respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary infections.

This project investigated the effect of operating parameters of a laboratory spray dryer on the characteristics of powders composed of Bovine Serum Albumin (BSA), L-leucine, and Trehalose Dihydrate, with the aim of optimizing their production for inhalation applications. The pre-study focused on optimizing spray-drying process parameters, including feed concentration (solid content), inlet temperature, nozzle diameter, spray gas flow rate, and feed solution flow rate. The main study used the optimized parameters from the pre-study to produce the final formulations. These powders were analyzed to determine their size, morphology, moisture content, and aerodynamic properties using light microscopy, laser diffraction, Scanning Electron Microscopy, bulk density measurements, water content measurements, Next Generation Impactor analysis, and Aerodynamic Particle Sizing.

The chosen spray drying conditions from the pre-study had an inlet temperature of 120 °C, an outlet temperature of 65 °C, a spray gas flow rate of 2.3 m³/h, and a feed rate of 1.7 ml/min. In the main study, formulations containing BSA or L-leucine were produced with high yields, above 75%. The d(0.5) of the particles are below 3.5 μm, with corrugated and raisin-like shape.

Among our tested formulations, 10BSA_20Leu performed best, with low residual moisture (2.6%), high bulk density (0.35 g/cm³), and Mass Median Aerodynamic Diameter (MMAD) between 2.5–2.9 μm, suitable for pulmonary administration. Trehalose-based powders with high leucine content showed better moisture resistance and dispersibility compared to pure trehalose, which had the lowest humidity resistance. Particle morphology and flowability were strongly related to the excipient type: leucine and BSA formed a corrugated surface that enhanced aerosolization but also increased bounce during NGI analysis. Samples enriched with 20% leucine displayed flake-like surface textures, attributed to crystalline excipient migration during drying. The effect of leucine was dose-dependent, indicating the importance of fine-tuning the excipient ratio for optimal inhalation performance. (Less)
Popular Abstract
Tiny Powders for Better Lung Treatments

Imagine inhaling medicine that fights lung diseases right where it’s needed—without pills or injections. In this project, we explored how to turn a protein-based solution into a dry powder suitable for inhalation, using a method called spray-drying. By carefully adjusting the recipe, including the addition of a natural amino acid called L-leucine, we aimed to improve how well the powder handles moisture and how efficiently it reaches the deeper parts of the lungs.

Lung diseases like asthma and chronic obstructive pulmonary disease (COPD) affect millions of people. Traditional inhalers often fail because moisture clogs the powder, wasting doses. We spray-dried a model protein (BSA), combined... (More)
Tiny Powders for Better Lung Treatments

Imagine inhaling medicine that fights lung diseases right where it’s needed—without pills or injections. In this project, we explored how to turn a protein-based solution into a dry powder suitable for inhalation, using a method called spray-drying. By carefully adjusting the recipe, including the addition of a natural amino acid called L-leucine, we aimed to improve how well the powder handles moisture and how efficiently it reaches the deeper parts of the lungs.

Lung diseases like asthma and chronic obstructive pulmonary disease (COPD) affect millions of people. Traditional inhalers often fail because moisture clogs the powder, wasting doses. We spray-dried a model protein (BSA), combined with a sugar (trehalose), and varying amounts of L-leucine, to form particles under 3.5 µm in size, small enough to be carried deep into the lungs.

We found that using 20% L-leucine helped the powder resist moisture compared with 10% or without L-leucine, improving flowability and reducing clumping in humid conditions. In a test setup simulating inhalation, these powders delivered about 60% of their content to the deeper lung regions. Additionally, the process yielded over 75% of the intended powder, which is promising from a manufacturing standpoint.

Why does this matter? In hot and humid climates, current inhalers sometimes fail to deliver consistent doses. Our findings suggest that this kind of formulation might improve performance in those environments. Under the microscope, the particles look like tiny, wrinkled raisins—shapes that help them float smoothly into airways rather than sticking to each other.

Although this study used a model protein, the same approach might one day be adapted for other drugs, including vaccines or antibiotics. The next steps include refining the technique and exploring how it could be scaled up in collaboration with the pharmaceutical industry. (Less)
Please use this url to cite or link to this publication:
author
Su, Jiapei LU and Zhu, Qianru LU
supervisor
organization
course
KLGM06 20251
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Spray-drying, BSA (Bovine Serum Albumin), L-leucine, trehalose;dry powders, protein based formulation, inhalation powder, pharmaceutical formulation, corrugated particles, aerodynamic study
language
English
id
9191763
date added to LUP
2025-06-02 09:42:24
date last changed
2025-06-02 09:42:24
@misc{9191763,
  abstract     = {{The pulmonary route has emerged as a promising strategy for delivering protein therapeutics, particularly for patients suffering from respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary infections.

This project investigated the effect of operating parameters of a laboratory spray dryer on the characteristics of powders composed of Bovine Serum Albumin (BSA), L-leucine, and Trehalose Dihydrate, with the aim of optimizing their production for inhalation applications. The pre-study focused on optimizing spray-drying process parameters, including feed concentration (solid content), inlet temperature, nozzle diameter, spray gas flow rate, and feed solution flow rate. The main study used the optimized parameters from the pre-study to produce the final formulations. These powders were analyzed to determine their size, morphology, moisture content, and aerodynamic properties using light microscopy, laser diffraction, Scanning Electron Microscopy, bulk density measurements, water content measurements, Next Generation Impactor analysis, and Aerodynamic Particle Sizing.

The chosen spray drying conditions from the pre-study had an inlet temperature of 120 °C, an outlet temperature of 65 °C, a spray gas flow rate of 2.3 m³/h, and a feed rate of 1.7 ml/min. In the main study, formulations containing BSA or L-leucine were produced with high yields, above 75%. The d(0.5) of the particles are below 3.5 μm, with corrugated and raisin-like shape.

Among our tested formulations, 10BSA_20Leu performed best, with low residual moisture (2.6%), high bulk density (0.35 g/cm³), and Mass Median Aerodynamic Diameter (MMAD) between 2.5–2.9 μm, suitable for pulmonary administration. Trehalose-based powders with high leucine content showed better moisture resistance and dispersibility compared to pure trehalose, which had the lowest humidity resistance. Particle morphology and flowability were strongly related to the excipient type: leucine and BSA formed a corrugated surface that enhanced aerosolization but also increased bounce during NGI analysis. Samples enriched with 20% leucine displayed flake-like surface textures, attributed to crystalline excipient migration during drying. The effect of leucine was dose-dependent, indicating the importance of fine-tuning the excipient ratio for optimal inhalation performance.}},
  author       = {{Su, Jiapei and Zhu, Qianru}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Spray-dried powders for inhalation}},
  year         = {{2025}},
}