(391g) Understanding High Shear Impact to Sodium Hyaluronate Size Control and Formulations

Sodium hyaluronate (NaHy) is widely used in many pharmaceutical or medical device formulations either without modifications as an excipient, crossed-linked to itself to form a hydrogel, or modified with a functional group or molecule to gain a relevant rheological quality attribute or to deliver an active pharmaceutical ingredient (API). High shear rates applied to NaHy solutions can induce selective chain scissions that can reduce molecular weight in a controllable manner. Understanding the shear-induced molecular weight changes can help produce defined molecular weights desirable for specific applications. It can provide a narrow distribution molecules that may be critical for specific therapeutic applications. Furthermore, it can significantly improve formulation processes bordering on caution when handling NaHy due to an overestimated risk of molecular weight degradation and viscosity loss.

Previous published work focused on hydrolysis, heat, and microwave as the main methods to degrade NaHy. These usually result in large polydispersity index (PDI) due to the random chain scissions inherent to the process. Previous work by Buchholz (2004) on linear polymers utilizing flow-induced chain scission demonstrated the ability to produce lower molecular weight while reducing the PDI to <1.2.

In this work, solutions of NaHy of wide range of molecular weights and concentrations were subjected to high shear rates to examine the impact of such shears on molecular weights. Solutions of NaHy with a molecular weight of 2000 kDa and concentrations of 1-5g/mL in water were sheared using an Ultra-Turrax T25 disperser fitted with an 18G attachment at speeds up to 20,000rpm with up to 2 hrs of shear. The samples were then analyzed using multi-angled light scattering MALS detector to identify their molecular weights and polydispersity indices.

Results suggest significant drop in molecular weight in some cases up to 40% with a PDI of <1.1. The distribution of molecular weight also showing trend towards localized distribution of 800-1000kDa. These results indicate that degradation can be controlled by adjusting flow speeds, geometry and other conditions to have defined, continuous, and reproducible processes that can produce monodispersed fractions.

In conclusion, this work can provide a new pathway for producing well defined narrowly distributed NaHy that allow for better control during drug product development to address unmet needs in the pharmaceutical and medical device industries.