Polysorbate degradation in biotherapeutic formulations: Identification and discussion of current root causes

Publication date: Available online 6 October 2018Source: International Journal of PharmaceuticsAuthor(s): Mridula Dwivedi, Michaela Blech, Ingo Presser, Patrick GaridelAbstractBiotherapeutic protein formulations are often high concentration liquid protein solutions, which are required to be stable under pharmaceutically relevant storage conditions and presence of external stress. Non-ionic detergents like polysorbate have been the most commonly used excipient to maintain formulation stability. Recently, particle formation in polysorbate containing biotherapeutic formulations has arisen as a major quality concern and potential patient risk factor. In this review, we provide a general overview into (i) degradation of polysorbates, (ii) polysorbate analytics, (iii) particle formation induced by polysorbate degradation and root causes thereof, (iv) particle composition and (v) various influencing factors that might lead to particle formation. Consequently, we explore the role of polysorbate degradation in particle formation. Additionally, various degradation pathways and the current discussed root causes are reviewed.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research