Preservation of rutin nanosuspensions without the use of preservatives

Abstract

Nanocrystals are used as universal approach to improve the bioactivity of poorly soluble active ingredients. They are produced by various techniques, typically yielding aqueous nanosuspensions, which are prone to microbial contamination. Preservation of nanocrystals is possible but might not always be feasible, as preservatives might interfere with other excipients in the formulations or with chemicals used in assays, cell cultures or animal models. Therefore, to enable an easier use of nanocrystals, preservative-free nanosuspensions would be a good alternative. In this study, rutin nanocrystals were frozen and stored for three months at -20 °C. The chemical, physical and microbial stability were monitored, and the results were compared to preserved nanosuspensions. The frozen nanosuspensions remained stable and possessed excellent stability over the whole time of storage, indicating that the freeze-thaw process is suitable for the production of preservative-free nanosuspensions with excellent long-term stability. The freeze-thaw process for nanosuspensions is a simple concept and is suggested as alternative, when preserved nanosuspensions cannot be used.