Investigating the Role of Particle Engineering and Excipients in the Processability of Pepsin Powder

Abstract

Pharmaceutical manufacturing of parenteral injections must be fine-tuned to yield a stable API through efficient production methods. Assessing a products processability is essential to ensure consistent manufacturing and safe drug administration, of which powder flowability and dissolution both have a direct impact. Spray drying is a particle engineering technique to modify these parameters, however, the relationship between spray drying conditions, particle properties and processability is not completely understood.
Spray drying was investigated as a particle engineering technique to determine its effects on the processability of protein powders. Pepsin was used as a model protein API to explore how both spray-drying conditions and excipient selection, specifically mannitol and lactose monohydrate, influence powder processability. The powders were produced with different spray drying conditions to generate samples with different particle size, morphology and solid-state properties. Processability was evaluated through powder flowability via ring shear testing and bulk and tap density measurements, and in vitro dissolution in PBS (pH 7.4, 15 ℃). These results were supported by BET surface area analysis and inverse gas chromatography (iGC) for surface energetics.
Spray drying produced amorphous samples which altered their hygroscopicity, surface area and cohesive behaviour. Mannitol-containing formulations showed the best flowability attributed to their spherical morphology and moderately high surface energy, while lactose-containing samples exhibited the poorest flow due to creased morphology and high total surface energy. From analysis of spearman correlation results, surface energetics proved to be the strongest predictor of flowability, while particle morphology was the best determinant of dissolution, with porosity and surface roughness enhancing wetting. Water content analysis was able to connect spray drying conditions, agglomeration and processability results.
All in all, there is no single parameter governing powder processability and it was instead the combination of morphological differences, excipient type, water content and surface energetics what affected powder performance. This emphasizes the importance of solid-state characterization when optimizing spray-dried formulations for pharmaceutical manufacturing.

Popular Abstract

How Powder Particles affect a Drug’s Success

Only about 10% of drug products that enter human critical trials ever receive approval for further production. Surprisingly, the problem is often not the drug itself but whether it can be turned into a product that behaves properly during manufacturing.
Many medicines are produced as powders that need to pass through various manufacturing steps before they can reach patients. During production, it is important that the powder flows smoothly through equipment, mixes evenly and is stable during storage. If the particles stick together, absorb too much moisture or behave unpredictably, manufacturing can slow down or fail completely. Processability problems like these cost pharmaceutical companies both time and money, which can delay important medicines from reaching patients.
To improve how powders behave, pharmaceutical companies often add substances called excipients. Two common examples are mannitol and lactose monohydrate. These ingredients can help protect sensitive drug compounds and make manufacturing easier and at the same time, they can also change the properties of the powder.
In this project, a model protein called pepsin was mixed with mannitol or lactose monohydrate to change its size, shape and surface structure, all of which had a major impact on processability. To modify the powder, spray drying was used, which is a process where liquid droplets are dried into small particles.
The results from the study showed that spray drying made the powder stickier and more humid, which affected how it flowed and dissolved. Overall, it was the size, shape and surface structure of the particles what had the biggest impact on processability. The powders with mannitol showed the best flow and dissolution compared to those with lactose. Interestingly, even powders that looked very similar still behaved different just because of small changes to their surface structure.
The main conclusion is that there is not a magic recipe to make the perfect pharmaceutical product so instead it’s important to carefully choose the process to make the powder, the excipients that are added, the shape of the particles, and other powder properties. By applying these findings to other protein-based medicines, researchers may be able to design drug products that are easier to produce, more stable and quicker to reach the patients who need them.

• author: Özsökmen Hick, Derya
• supervisor: Stephen Burleigh; Zacharias Brimnes Visby Damholt; Jari Pekka Pajander
• organization: Pharmaceutical Technology (master); Food Technology and Nutrition (M.Sc.)
• course: KLGM06 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Chemistry
• keywords: parenteral injections, spray drying, processability of protein powders, pharmaceutical formulation
• language: English
• id: 9233395
• date added to LUP: 2026-06-10 14:27:25
• date last changed: 2026-06-10 14:27:25