Producing highly concentrated, low-viscosity protein or peptide therapeutics is one of the major challenges in today’s pharmaceutical industry, especially during the pre-formulation development stage, where viscosity measurement is particularly important. Accurate viscosity measurements can provide important information about protein or peptide formulations, such as differences in protein size and protein-protein interactions. CD Formulation has extensive experience in protein or peptide viscosity characterization, and our protein scientists utilize state-of-the-art analytical techniques and adhere to industry standards to ensure the highest quality of viscosity analysis.
The effectiveness of protein and peptide therapeutics depends largely on the active form of the protein and peptide. Only in its native form can it exert its full biological function. With the continuous development of the pharmaceutical industry, high-concentration protein solutions for subcutaneous injection have become a research hotspot.
High-concentration protein solutions are complex fluids that contain not only proteins but also surfactants, stabilizers, and salts. These components interact with each other and can affect the viscosity of the solution. In addition, beyond a certain concentration (depending on the protein), the viscosity of the protein solution may increase dramatically, leading to a series of instability problems such as aggregation, which in turn leads to the loss of the biological function of the protein. Therefore, accurate characterization of the viscosity of proteins or peptides is a key step in the protein peptide formulation development process.
Fig. 1 Vibro viscometer for protein/peptide viscosity characterization.
The viscosity of protein or peptide solutions must be characterized to ensure their stability during development. At CD Formulation, our viscosity analysis team applies a range of advanced equipment and analytical techniques to perform viscosity measurements to further probe how formulation changes affect protein or peptide solutions. Molecular interactions are probed by introducing and quantifying changes in rheological properties when formulation changes occur.
To determine solution stability and viscosity changes, our expert team combines dynamic light scattering, microfluidics, rheology, glass capillary viscometer, small angle X-ray scattering (SAXS), rolling ball viscometer and other technical strategies to obtain accurate data on viscosity, which reflects differences in protein size and the formation of complex structures or networks caused by various types of molecular interactions.
In addition to viscosity characterization, our scientists will provide support for viscosity control of your therapeutic proteins and peptides throughout the formulation development stage, including the use of small molecule excipients (such as amino acids and salts) to reduce protein solution viscosity or reduce protein-protein interactions to reduce viscosity. A common strategy is to stabilize proteins in solution and reduce viscosity by adding arginine, an amino acid that is charged at neutral pH and whose side chain consists of a three-carbon chain with a charged guanidine group at the end.
Available Analysis Projects | Technologies |
Torsional rheometer | We determine the exact molecular weight of proteins using high-resolution mass spectrometry (Orbitrap, QToF) and a range of other techniques such as size exclusion chromatography (SEC), and SDS-polyacrylamide gel electrophoresis. |
Dynamic light scattering | We obtain electropherograms and homogeneity and purity data for proteins and peptides using capillary isoelectric focusing (CIEF/iCIEF), polyacrylamide gel electrophoresis, SDS-polyacrylamide gel electrophoresis, and capillary electrophoresis. |
Viscometer | We use UV/visible absorbance of product solutions of known protein content to accurately determine the extinction coefficient and use amino acid composition analysis to quantify the concentration of protein in the solution. |
Microfluidics | We use chromatography and gel/capillary electrophoresis for isomer patterning as well as impurity detection. |
Photon correlation spectroscopy | We perform protein aggregation studies using dynamic light scattering, multi-angle laser light scattering (MALS), and sedimentation velocity analytical ultracentrifugation (SV-AUC). |
Small angle X-ray scattering (SAXS) or X-ray solution scattering | They are used to measure the apparent particle size or apparent molecular weight to estimate the viscosity of protein solutions. |
Particle Diffusometry | We perform protein and peptide structural analysis using far- and near-UV circular dichroism (CD), nuclear magnetic resonance (NMR), infrared (FTIR), or ultraviolet-visible spectroscopy. |
Published Data
Technology: Development strategy for concentrated antibody solution with high viscosity
Journal: MAbs.
IF: 5.3
Published: 2016
Results:
The authors describe general strategies and guidelines for selecting low viscosity drug candidates or optimizing lead drug candidates to reduce viscosity during the early stages of therapeutic antibody discovery. In addition, strategies for formulation optimization and excipient design are proposed for drug candidates already in advanced product development by exploring the effects of formulation components, such as buffers, pH, salts, surfactants, and other excipients, on intermolecular interactions.
Fig. 2 Concentration dependence of viscosity of antibody solutions under identical buffer conditions. (Tomar DS, et al., 2016)
At CD Formulation, we understand the importance of viscosity analysis in the high-concentration protein solutions development and manufacturing process. Please feel free to contact us if you are interested in our services. We will provide you with the most professional advice and support to ensure the smooth launch and implementation of your project.
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