Impact of electroviscous effect on viscosity in developing highly concentrated protein formulations: Lessons from non-protein charged colloids

Abstract

Graphical abstract

Development of syringes and vials for delivery of biologics: current challenges and innovative solutions

“…Pharmaceuticals in prefilled syringes should be manufactured with high protein concentrations (50-180 mg/mL) to reduce dosage volume. High protein concentration may form networks of proteins, causing protein aggregates to form [50,51]. Inorganic or organic salts enable the reduction of viscosity by disrupting the electrostatic attraction of proteins [50].…”

“…High protein concentration may form networks of proteins, causing protein aggregates to form [50,51]. Inorganic or organic salts enable the reduction of viscosity by disrupting the electrostatic attraction of proteins [50]. Clogging of the staked needle should also be taken care of.…”

Discovery-stage identification of drug-like antibodies using emerging experimental and computational methods

“…49,[51][52][53] Local electrostatic and hydrophobic interactions, amplified by molecular crowding in highly concentrated solutions, have often been implicated in antibodies that display high self-association and viscosity. [54][55][56][57] In-depth investigations of individual antibodies have provided some insight into possible mechanisms of self-association, and can help to inform their computational identification and motivate rational protein design. For example, the presence and distribution of charged residues in the antigen-binding site have been implicated in the unacceptably high viscosity of a well-studied antibody (omalizumab).…”

Scaling of Shear Rheology of Concentrated Charged Colloidal Suspensions across Glass Transition

“…Moreover, many technologically important colloidal systems are suspensions of charged colloids. The electrostatic long-ranged repulsive interaction between colloidal particles, which is jointly controlled by particle surface charge and solution salinity, 8−12 can dramatically enhance the shear viscosity through the electroviscous effect, 10,11,13,14 leading to a glass transition at a much lower volume fraction than that of the hard sphere counterpart. 15,16 However, in contrast to hard sphere systems, 17−19 the direct and quantitative relations between rheological properties of charged colloids and their system control parameters, 10 especially suspension salinity, remain largely elusive despite their technological importance.…”

“…Moreover, many technologically important colloidal systems are suspensions of charged colloids. The electrostatic long-ranged repulsive interaction between colloidal particles, which is jointly controlled by particle surface charge and solution salinity, − can dramatically enhance the shear viscosity through the electroviscous effect, ,,, leading to a glass transition at a much lower volume fraction than that of the hard sphere counterpart. , However, in contrast to hard sphere systems, − the direct and quantitative relations between rheological properties of charged colloids and their system control parameters, especially suspension salinity, remain largely elusive despite their technological importance. This is because the rheology is very sensitive to interparticle interactions between charged colloids, whereas its theoretical treatment is rather complicated for high concentrations or strong shear flows that can cause substantial overlapping or distortion of the shapes of the electrical double layers of ions surrounding the charged colloids.…”