As the field of biopharmaceutics continues to evolve, the pharmaceutical industry is striving to develop more convenient and patient-friendly drug delivery approaches, such as subcutaneous drug delivery. However, a significant challenge in this area is the high viscosity of highly concentrated monoclonal antibody formulations, primarily due to the limited volume that can be administered subcutaneously. This presents a technological challenge in the development of such medicines. One strategy to mitigate the effect of intermolecular interactions is the inclusion of excipients with viscosity-reducing properties. Furthermore, the addition of such excipients may also impact the stability and safety of the product.
The objective of master thesis was to investigate the effect of novel excipients on the viscosity reduction in highly concentrated formulations of IgG monoclonal antibodies and to assess their effect on monomer stability in the prepared samples. Viscosity measurements were conducted using a viscometer. Aliquots of samples were stored under a pair of different conditions to assess the impact of the tested substance on the stability of the antibody.
Our study demonstrated that the viscosity of highly concentrated solutions of monoclonal antibodies can be reduced to levels suitable for subcutaneous drug delivery using one or a combination of tested substances. Furthermore, we demonstrated that the loss of the monomeric form of the antibody was comparable across samples with added tested substances kept under the same conditions (time and temperature). However, differences in degradation products were observed between the samples in question, namely the formation of aggregates or molecular species smaller than antibodies.
The results of our study provide a valuable reference for future research, allowing investigators to determine the efficacy of the tested excipients in reducing the viscosity of monoclonal antibody formulations. Furthermore, it highlights the necessity to comprehend the underlying mechanisms by which the tested substances exert their effect. By elucidating these mechanisms and identifying the structural elements responsible for this effect, it will be possible to design a pharmacophore-like model that will facilitate the discovery of new excipients with viscosity-reducing properties for highly concentrated solutions of monoclonal antibodies.
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