Microstructural analysis of the fast gelling freeze-dried sodium hyaluronate

• Freeze-dried sodium hyaluronate (NaHA) samples were prepared.
• Reconstitution of freeze-dried NaHA showed fast gelling ability.
• No crystalline to amorphous transition of NaHA was observed.
• More ordered but highly porous polymer structure formed due to the presence of phosphate salts in the course of freeze-drying.
• Supramolecular ordering did not cause functionality-related alteration, viscoelasticity was preserved for reconstituted gels.

Although sodium hyaluronate is a very unstable and heat sensitive molecule, it can remain relatively stable during the freeze-drying process. Aqueous sodium hyaluronate (NaHA) gels were prepared and the obtained samples were freeze-dried. The freeze-dried NaHA samples showed fast gelling ability meanwhile preserved their initial viscoelasticity even after reconstitution. The microstructure of gels obtained from raw substance and freeze-dried NaHA samples was characterized with positron annihilation lifetime spectroscopy and X-ray diffraction patterns while their functionality-related macrostructural properties were tested based on their rheological behavior. The presence of phosphate salts improved the formation of ordered supramolecular structure retaining water in the free volume holes of the polymer chains characterized with decreased ortho-positronium lifetime values. This property may be advantageous in the development of a freeze-dried NaHA injection dosage form.

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