Recent quality by design approaches for process optimization and quality enhancement of dry powder inhalers

Background: Dry powder inhalers (DPIs) are a widely used method for delivering drugs directly to the lungs, where particle size and design critically influence inhalation efficiency and consistency. To reach deep respiratory areas, particles need an aerodynamic diameter of 5 μm or smaller. However, these small particles are highly cohesive, requiring formulation techniques such as blending with coarse carriers like lactose or modifying density, porosity, and surface energy through methods like spray drying to ensure optimal performance. Area covered: This review examines the essential processes involved in DPI manufacturing, focusing on particle engineering techniques and formulation processes such as drug blending and filling. The Quality by Design (QbD) approach is explored as a comprehensive framework for DPI process optimization, emphasizing particle characteristics and process factors that impact product quality. Key QbD methodologies, including risk management and statistical design of experiments, are highlighted in recent studies that showcase their contributions to DPI quality, safety, and efficacy. Expert opinion: The integration of scientific design principles and statistical analysis into DPI development represents a major advancement in ensuring quality and performance. By leveraging QbD methodologies, DPI manufacturing can achieve enhanced reproducibility, better control of critical quality attributes, and improved therapeutic outcomes. Continued research into QbD-driven process optimization is expected to advance the safety and effectiveness of DPIs for pulmonary drug delivery.