Process optimization of Lyophilization for long term stability of Edaravone nanosuspension

Abstract

Downstream processing during nanosuspension formulation can impose stress on particles, potentially leading to Ostwald ripening. To maintain its integrity throughout storage, solidification is important. This study thoroughly investigated the effect of cryoprotectant type and concertation, freezing temperature, cooling rate and primary drying temperature on redispersibility and particle size along with a six-month stability study. Optimal results were achieved using trehalose, low freezing temperatures, slower freezing rates, and extended secondary drying times. Additionally, the lyophilized product demonstrated enhanced aqueous saturation solubility. Solid-state characterization and residual moisture content analysis were performed on the optimized formulation. A robust lyophilization protocol was successfully developed, allowing the reconstitution of solid nanocrystals with minimal changes to their physicochemical properties. Over the six-month period, formulation exhibited the greatest stability, with negligible changes in particle size and excellent redispersibility. Lyophilization can improve the efficiency of the prepared nanosuspension based drug delivery system.