Subcutaneous (SC) injections, offering benefits like self-administration and cost reduction, face challenges with injection-site pain, especially in high-dose monoclonal antibodies (mAbs) formulations requiring high concentration within a 2 mL volume limit. This article explores strategies to mitigate such pain, focusing on formulation aspects like buffer choice, pH, and viscosity. Citrate, often used as a buffer, is scrutinized for its pain-inducing properties compared to alternatives like histidine or phosphate. The discussion includes how formulation adjustments, buffer selection, and excipients can reduce SC injection-site pain, enhancing patient compliance.

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