Physicochemical Comparison of Kolliphor HS 15, ELP, and Conventional Surfactants for Antibody Stabilization in Biopharmaceutical Formulations.

Stabilization of therapeutic protein formulations with nonionic surfactants such as Polysorbate 20 (PS20), Polysorbate 80 (PS80), or Poloxamer 188 (P188) is imperative to avoid critical loss of the active pharmaceutical ingredient by aggregation or adsorption onto different types of interfaces. In the present work, we have characterized the interfacial activity of the aforementioned surfactants, alone and in competition with antibodies, in comparison to two other excipients with approval for use in parenteral applications, Kolliphor HS 15 (HS15) and Kolliphor ELP (ELP). To this end, we applied a comprehensive suite of experimental techniques, including tensiometry, interfacial rheology, and quartz-crystal microbalance with dissipation monitoring (QCM-D). The obtained data shows important differences between the surfactants as well as a clear influence of the type of interface considered on the observed behavior. In order to link these physicochemical results to the performance of the chosen surfactants in the stabilization of antibodies, we performed another series of tests to quantify protein aggregation (i.e., the formation of (sub)visible particles in formulations under stress) as well as the release of oil from siliconized vials. In addition, the stability of the surfactants against enzymatic degradation was investigated. It is demonstrated that HS15 can compete with the widely used polysorbates in terms of interfacial activity and protein stabilization, while offering higher robustness against degradation by a lipase and an esterase. On the other hand, P188 shows poor interfacial activity but can still suppress the aggregation of at least some proteins, indicating that different mechanisms of stabilization are at play. Our findings and the broad spectrum of tests described in this work are instructive toward a better understanding of protein stabilization in distinct primary packaging systems through surfactants in aqueous formulations.