Molecular Weight (MW) Testing of Excipients

Molecular weight is the molar mass distribution of the polymer chain, and is a key property used to characterize polymer-based products. MW varies widely within polymers of the same chemical nature, which can be problematic for regulated industries where products must meet stringent levels of consistency, such as the pharmaceutical industry. The molecular weight of polymeric excipients often has a direct effect on their mechanical properties, thermal behavior and viscosity characteristics. Modern analytical techniques are available to characterize the molecular weight of polymers, each providing useful information on the effect of molecular weight on the measured properties. BOC Sciences has introduced gel permeation chromatography (GPC) and dilute solution or intrinsic viscometry (IV) to provide reliable molecular weight testing services.

MW Testing Using GPC

Principle of GPC Analysis

GPC technology is an innovative and the most commonly used method for determining the molecular weight of samples in solution. In GPC, a dilute solution of the analyte is prepared using a optimal solvent for the analyte to ensure good dissolution and expansion of the polymer chains in solution. The solution is then injected into a packed column containing a distribution of pore size that separates the polymer chains by size. After the dilute solution containing the analyte leaves the column, the refractive index detector is used to calculate its MW according to their elution time from the column.

Figure 1. GPC-MALS used in the molecular weight testing for a polymeric excipient. (Auch, C.; et al. 2018)

GPC Analysis Services

At BOC Sciences, in addition to the standard refractive index detector, our experts employ additional multi-angle light scattering technique to provide absolute molecular weight and viscosity determination to offer a universal calibration method. We can perform GPC on water-soluble polymeric excipients and natural excipient materials as well as organic soluble materials:

• A range of complex polymer systems are employed for tablet coating. These include biopolymers such as proteins, naturally-derived carbohydrates and synthetic polyolefins. Polyolefins typically have wide molecular weight distributions with high polydispersity values. The molecular weights of polyolefins can vary by several orders of magnitude depending on the type of polyolefin and its application. BOC Sciences’ GPC method is suitable for high-resolution characterization of polyolefins for pharmaceutical packaging. Our GPC systems can separate molecular compartments with molecular weights ranging from 500 to 10,000,000.
• Alginic acid, potassium alginate and sodium alginate are common natural polymers used in the manufacture of pharmaceutical excipients. Our GPC-NMR coupling technology can be used to measure the molecular weight of these alginates to help our customers accurately characterize the composition and variability of these excipients.
• For the development and validation of some complex pharmaceutical excipients such as copolymers containing alkyl methacrylate or alkyl acrylate that lack specific testing, our GPC method is also suitable for measuring their average molecular weight and polydispersity.

Dilute Solution Viscometry Characterization of MW

Like GPC method, dilute solution viscometry describes the molecular weight of a material based on its size in solution, which in turn affects its viscosity. The solution flows through a fine capillary in a viscometer, and the flow time is measured relative to the flow time of the neat solvent. The results are usually reported as relative viscosity or inherent viscosity. If a range of concentrations are measured, the intrinsic viscosity can be calculated and the molecular weight can be determined by using Mark-Houwink parameters of the polymer-solvent system.

Figure 2. Dilute solution viscometry of polymers. (Wei, L.; Jimmy, M. 2021)