Spray-dried powders for inhalation

Abstract

Spray drying is a widely utilized method for producing protein pharmaceutical powders due to its cost-effectiveness, efficiency, ability to extend shelf life and tailor particle characteristics. These advantages make spray drying an optimal option to produce dry powders suitable for inhalation.
Dry powders are extensively used in treating lung diseases primarily due to their increased stability, their ability to preserve drug activity, and achieve high deposition efficiency in the lungs, compared to other delivery forms. Therefore, protein pharmaceutical powders can be produced with spray drying and tailored specifically for inhalation.
This project aimed to produce spray-dried protein powders for inhalation using specific spray drying conditions and excipients. The research was conducted in two parts: the pre-study and the main study. The pre-study identified the ideal spray drying conditions for inhalation powders containing only lactose or trehalose dihydrate. The main study focused on spray drying powders with Bovine Serum Albumin as the active pharmaceutical ingredient and trehalose dihydrate and L-leucine as excipients. These powders were analyzed to determine their size, morphology, and aerodynamic properties using laser diffraction, light microscopy, bulk density measurements, Scanning Electron Microscopy, Next Generation Impactor analysis and Aerodynamic Particle Sizing.
All spray-dried powders produced under different conditions were in the size range between 3.5-5 μm. In the pre-study pure powders containing lactose or trehalose dihydrate were smaller, smooth, and spherical. The chosen spray drying conditions had an inlet temperature of Tin = 175 oC, an outlet temperature of Tout = 73 oC, aspirator rate of 32 m3/hr, and pump rate of 5 mL/min.
In the main study, complex powders containing BSA, and L-leucine were produced with a high yield, above 75%. They contained particles between 4-5 μm, with corrugated, and raisin-like shapes. Samples with L-leucine exhibited a flake-like surface, likely due to crystalline L-leucine on the surface. NGI analysis showed that all powders containing BSA had an aerodynamic diameter below 5 μm, suitable for efficient aerosolization. The sample with the highest amount of L-leucine (27% w/v) had the highest Fine Particle Fraction at 49.3%.
The findings suggest that spray drying was a suitable method to produce inhalable protein powders with high yield. The addition of BSA and L-leucine resulted in raisin-shaped particles, while higher L-leucine concentrations improved dispersibility and aerosolization performance.

Popular Abstract

Spray drying is a method that has been used widely in the pharmaceutical industry to produce powders containing therapeutic drugs. It is a method that takes a liquid formulation, sprays it into a chamber in the form of droplets, and dries it with high temperature air. Then the solvent evaporates from the droplets, producing solid particles in powder form. It is a cost-effective method which is easy and quick to use.
The powders produced with spray drying can be tailored for use in inhalation. These dry powders are made to cure lung specific diseases and need to have specific size and shape to have a therapeutic effect in the lungs. One specific characteristic required is that the aerodynamic size of the particles is below 5 μm. The aerodynamic diameter (AD) of the particles is the size of a sphere (density 1 g/cm³) that moves at the same speed as the particles when an individual inhales.
To make dry inhalation powders with spray drying, two things need to be considered: the effect of the spray drying conditions and the effect of the formulation on the powder characteristics.
This study examined both objectives by using three sets of spray drying conditions on pure lactose and trehalose dihydrate powders (pre-study) and changing the additives in the formulation to study their effect on the particles (main study).
Bovine Serum Albumin, a standard protein, was used as the model drug in the formulation, and L-leucine, an amino acid, was added to the formulation in different concentrations to improve the aerosol performance of the powders.
The powders were analyzed with different methods to determine their size, shape, surface morphology and aerosol characteristics such as the aerodynamic diameter and their efficiency as an inhalation powder.
It was found that the powders produced had the ideal aerodynamic size to perform well as aerosol powders (<5 μm) and reach the deep part of the lungs. They were also irregularly shaped which typically improves aerosol performance. Additionally, it was discovered that L-leucine improves the powders ability to reach the lungs and have a therapeutic effect.

• author: Kousouli, Elli Martina
• supervisor: Anna Fureby; Kyrre Thalberg
• organization: Food Technology and Nutrition (M.Sc.)
• course: KLGM06 20241
• year: 2024
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: Spray drying, dry powders, protein, inhalation, aerodynamic diameter, trehalose, L-leucine, Bovine Serum Albumin, corrugated particles, pharmaceutical formulation
• language: English
• id: 9162159
• date added to LUP: 2024-06-13 10:15:23
• date last changed: 2024-06-13 10:15:23