TY  - JOUR
T1  - High-Concentration Protein Formulations Under Injection Constraints: A Critical Review of Reversible Self-Association, Viscosity, Interfacial Damage, and the Trade-Off Between Dose Volume and Deliverability
A1  - Michael Tan
A1  - Laura Bianchi
A1  - Johan de Vries
A1  - Farah Aziz
A1  - Elena Rossi
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2026
VL  - 15
IS  - 4
DO  - 10.51847/BjAlY5vbmS
SP  - 173
EP  - 184
N2  - 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.
UR  - https://ijpras.com/article/high-concentration-protein-formulations-under-injection-constraints-a-critical-review-of-reversible-2lvbnzxc9bg5dhh
ER  -