The glass transition and sub-T(g)-relaxation in pharmaceutical powders and dried proteins by thermally stimulated current

Abstract

The main goal of the study was to evaluate the applicability of thermally stimulated current (TSC) as a measure of molecular mobility in dried globular proteins. Three proteins, porcine somatotropin, bovine serum albumin, and immunoglobulin, as well as materials with a strong calorimetric glass transition (T(g)), that is, indomethacin and poly(vinypyrrolidone) (PVP), were studied by both TSC and differential scanning calorimetry (DSC). Protein/sugar colyophilized mixtures were also studied by DSC, to estimate calorimetric T(g) for proteins using extrapolation procedure. In the majority of cases, TSC detected relaxation events that were not observed by DSC. For example, a sub-T(g) TSC event (beta-relaxation) was observed for PVP at approximately 120 degrees C, which was not detected by the DSC. Similarly, DSC did not detect events in any of the three proteins below the thermal denaturation temperature whereas a dipole relaxation was detected by TSC in the range of 90-140 degrees C depending on the protein studied. The TSC signal in proteins was tentatively assigned as localized mobility of protein segments, which is different from a large-scale cooperative motions usually associated with calorimetric T(g). TSC is a promising method to study the molecular mobility in proteins and other materials with weak calorimetric T(g).