Optimisation of Blend Uniformity in a Low Dose Dry Powder Inhaler Formulation: Investigating API and Excipient Interactions and Process Parameters

Abstract

This dissertation investigates the optimisation of blend uniformity in low dose dry powder inhaler (DPI) formulations, focusing on the interplay between active pharmaceutical ingredient (API) and excipient interactions, as well as critical process parameters such as blending time and speed. Through a combination of literature review, experimental analysis, and scale up studies, the research explores how material properties and mechanical energy inputs influence blend performance. Findings revealed that while process optimisation reduced variability (%RSD) and improved uniformity in several batches, three out of eight failed to meet acceptance criteria, and most exhibited high maximum API content values. Particle size distribution (PSD) and scanning electron microscopy (SEM) analysis confirmed that excipient morphology played a key role in API adhesion and dispersion, with coarse lactose enhancing flow and fine lactose improving binding. Successful scale up from low shear to high shear blending using matched tip speeds demonstrated reproducibility and robustness, validating the hypothesis that mechanical energy translation supports consistent blend quality. However, limitations such as manual sampling bias, narrow material scope, and lack of real-time analytical tools were acknowledged. This study contributes a scalable framework for DPI blend optimisation, emphasising the need for integrated formulation and process development. It advocates for a flexible, science-driven approach to manufacturing that enhances product quality and supports commercial feasibility.