Approaches to Alleviating Subcutaneous Injection-Site Pain for Citrate Formulations

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Pharmaceutical Technology, Pharmaceutical Technology-06-02-2020, Volume 44, Issue 6
Pages: 32–37

The authors compare formulations containing citrate with other buffers in reducing subcutaneous injection-site pain and discuss a formulation and excipients selection strategy.

Subcutaneous (SC) injection is a method of administering medication as a bolus under the skin that is often used as an alternative delivery method for oral administration and now also for high-dose administration through intravenous (IV) infusion. SC injection provides flexibility in dosage form and options of self-administration outside of a health care setting. It may also help reduce drug cost and increase patient compliance. Biopharmaceuticals intended for delivery as SC injections are commonly formulated at an acidic pH with a variety of stabilizing agents and buffers, including histidine, phosphate, and citrate. In addition, SC injections are limited by a maximum injection volume of 2 mL or less per dose, making SC injection of monoclonal antibodies (mAbs) challenging. MAbs requires high dose; therefore, for SC injection it must be formulated at high concentration so the total injection volume remains within 2mL. An increase in protein concentration in the formulation increases the solution viscosity, which may cause increased injection-site pain in an SC dosage. The authors will discuss how formulations containing citrate compare to other buffers in reducing SC injection-site pain and discuss a formulation and excipients selection strategy that formulators can use to mitigate the risk of injection-site pain due to buffer, pH, and viscosity. 




Submitted: Nov 18, 2019
Accepted: Dec. 18, 2019

About the authors

Arvind Srivastava, PhD*, is technical fellow, and Ger Brophy, PhD, is executive vice-president, Biopharma Production; both are at Avantor. Meera Agarkhed was a senior manager, Technology & Innovation, at Avantor.

*To whom all correspondence should be addressed.

Article Details

Pharmaceutical Technology
Vol. 44, No. 6
June 2020
Pages: 32–37


When referring to this article, please cite it as A. Srivastava, et al., “Approaches to Alleviating Subcutaneous Injection-Site Pain for Citrate Formulations,” Pharmaceutical Technology 44 (6) 2020.