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

Sammanfattning

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.