FREE-SOLVENT MODEL OF OSMOTIC-PRESSURE REVISITED - APPLICATION TO CONCENTRATED IGG SOLUTION UNDER PHYSIOLOGICAL CONDITIONS

The osmotic pressure measurements of bovine immune-gamma globulin in p hosphate-buffered solution at pH 7.4 and 0.13 M total salt concentrati on were extended to near saturation concentrations for ambient tempera ture. The osmotic pressure at the highest measured concentration of 42 4 g/L was 4.18 psi (28.3 kPa). A free-solvent model, considering solut e-solvent interaction in the concentration variable, provided an excel lent fit to observed osmotic pressure nonideality at even the highest protein concentration. The calculated mass of hydrated solvent compare d with amounts determined from water-O-17 magnetic resonance for other globular proteins. This model provides an improved correlation to the data over virial equations (truncated to the third term) when only so lute-solute interactions are considered. The use of mole fraction as t he composition variable was critical in obtaining the excellent fit of the free-solvent model. A combination of the free-solvent correction for the concentration variable coupled with models incorporating solut e-solute interaction, such as a virial expansion, will be necessary to generally describe the osmotic pressure of protein solutions for all concentrations. (C) 1998 Academic Press.