High-dose subcutaneous protein administration places pharmaceutical formulation under competing constraints: dose volume, solution flow, physical stability, device capability, and patient-facing delivery requirements. Concentrating a biologic may reduce injection volume while amplifying molecular crowding, reversible self-association, viscosity, and susceptibility to process- or container-associated stress. This critical review examines how those mechanisms are observed and interpreted, focusing on the distinction between protein interaction measurements, rheological responses, interfacial particle formation, and actual drug-product delivery. Evidence from colloid models, scattering, diffusion assays, protein-specific formulation experiments, and device-oriented reviews supports a conditional account: concentration-dependent rheology is strongly dependent on protein sequence and solution conditions, whereas particle formation under interfacial stress follows partly separate pathways. Shortcomings include assay-specific observability, incomplete cross-study comparability, and limited direct coupling of molecular measurements to complete injection-system outcomes. Consequently, selection between high-concentration/low-volume and lower-concentration/larger-volume presentations should be assessed at the level of the integrated formulation–container–device combination, without treating any single molecular predictor as a universal deliverability criterion.
IJPRAS
