Solution properties of hyaluronic acid and comparison of SEC‐MALS‐VIS data with off‐line capillary viscometry

Extensive study of solution properties of sodium hyaluronate including about 140 samples and covering broad molar mass range was carried out by classical viscometry using an Ubbelohde capillary viscometer and by combination of size‐exclusion chromatography with a multi‐angle light scattering detector and an on‐line viscometer. The study also involved critical overview of literature data of Mark‐Houwink relation for sodium hyaluronate. Continuous decrease of the Mark‐Houwink exponent with increasing molar mass to the values markedly lower than those typical of linear random coils in thermodynamically good solvents was observed. This fact was attributed to branched molecular structure of hyaluronic acid as a result of unknown side reactions during the manufacturing process. The molar mass dependence of the second virial coefficient was determined and proved aqueous salt solutions to be thermodynamically good solvents for sodium hyaluronate.