Analysis of sub-visible particles in complex injectable formulations

摘要

Complex injectable formulations, such as protein therapeutics, controlled release systems and cell therapy products, are gaining a paramount position in the therapy of many life-threatening and chronic diseases. Most of these products have in common that sub-visible particles (SVP), i.e., particulate matter in the size range of about 1 – 100 µm, are criticalquality attributes. Most protein therapeutics are liquid or freeze-dried formulations in which the presence of SVP is unwanted; many injectable controlled release systems are based on particulate drug delivery systems in the sub-visible size range; and cell concentration and viability are important characteristics of cell therapy products. With the continuousimprovement of existing and emerging particle analysis techniques, the potentials of these tools in addressing current characterization challenges in the field of complex injectable formulations have to be investigated. Therefore, the aim of this thesis was to develop methods, based on a set of state-of-the-art particle analysis techniques, for characterization of pharmaceutically relevant sub-visible particles and to study the value of these methods in the characterization of complex injectable formulations.