Local irritation and inflammation at the site of administration are a common side effect following administration of parenteral formulations. Biological effects of surface (interfacial) activity in solutions are less well investigated than effects caused by other physico-chemical parameters such as pH and osmolality. The interfacial activity in different systems, including human plasma, typical amphiphilic substances with fundamental biological relevance such as free fatty acids, anesthetic depot formulations and six different antibiotics was measured. The relative interfacial pressure, and/or concentration of active substance, required to obtain 50% of the maximal attainable effect in terms of interfacial pressure were calculated. The aim was to test the hypothesis that these parameters would allow comparison to biological effects reported in in vivo studies on the investigated substances. The highest interfacial activity was found in a triglyceride/plasma system. Among the antibiotic tested, the highest interfacial activities were found in erythromycin and dicloxacillin, which is in accordance with previous clinical findings of a high tendency of infusion phlebitis and cell toxicity. Independently of investigated system, biological effects were minimal below a 15% relative increase of interfacial activity. Above 35-45% the effects were severe. Interfacial activity in parenteral formulations may well cause damages to tissues followed by inflammation. (C) 2015 Elsevier B. V. All rights reserved.