When Does Magnesium Stearate Improve Carrier-Based Dry Powder Inhalers (DPI) Performance? A Critical Review of Material, Process, and Formulation Factors

Magnesium stearate (MgSt), although well established as a pharmaceutical lubricant in solid oral dosage forms, plays a more complex role in carrier-based dry powder inhalers (DPIs), where it functions as a surface modifier and force control agent (FCA). In DPI formulations, MgSt can influence powder rheology, moisture resistance, interparticulate interactions, and aerosolization efficiency; however, these effects depend not simply on its presence or concentration, but on whether effective surface modification is achieved. This review critically evaluates experimental evidence on MgSt-mediated particle coating in carrier-based DPIs, with particular emphasis on how material attributes, particle cohesion and surface area, process energy, coating strategy, and MgSt concentration interact to determine coating efficiency and formulation performance. By integrating these factors, the review aims to provide a mechanistic framework for selecting and optimizing MgSt coating strategies and to identify methodological priorities for future research. The available evidence indicates that process energy is a major determinant of coating efficiency. High-energy techniques, particularly mechanofusion, can effectively modify highly cohesive micronized particles that are difficult to coat using conventional blending, whereas high-shear blending may provide sufficient energy for surface modification of larger, coarse lactose carriers. Mechanical milling represents a distinct strategy in which particle-size reduction and surface modification occur simultaneously. Direct comparison between coating approaches remains difficult because studies differ in MgSt grade, carrier and API properties, particle size distribution, processing conditions, and methods used to assess coating efficiency. MgSt generally improves aerosolization by modifying cohesive and adhesive interactions, but the magnitude of this effect is formulation-specific. Improvements in fine-particle delivery depend on MgSt particle size and specific surface area, the properties and surface area of the particles being coated, process energy, and the resulting coating efficiency. Consequently, increasing MgSt concentration does not necessarily improve performance, and excessive amounts may lead to overlubrication or MgSt agglomeration. Despite considerable progress, important knowledge gaps remain regarding how MgSt coating translates into improved DPI performance. Further studies integrating material properties, processing conditions, surface modification, and formulation performance are needed to establish more robust relationships between coating strategy and functional outcomes. Such knowledge may support more rational and formulation-specific use of MgSt in carrier-based DPIs.