The effect of excipients on the molecular mobility of lyophilized formulations, as measured by glass transition temperature and NMR relaxation-based critical mobility temperature

Purpose, The dependence of the molecular mobility of lyophilized formulatio ns on pharmaceutical polymer excipients was studied. Molecular mobility as determined by NMR relaxation-based critical temperature of molecular mobili ty (T-mc) and glass transition temperature (T-g) is discussed in relation t o the plasticizing effect of water in formulations. Methods. The T-mc and T-g of lyophilized gamma-globulin formulations contai ning 6 different polymer excipients such as dextran, polyvinylpyrrolidone ( PVP) and methylcellulose (MC) was determined by NMR and DSC. The molecular mobility of water in the formulations was determined by proton NMR and diel ectric relaxation spectrometry (DRS). Results. T-mc varied with polymer excipients. T-mc increased as the ratio o f bound water to mobile water increased and as the molecular mobility of mo bile water decreased. The formulation containing MC exhibited a lower T-mc than the formulation containing dextran because of the smaller ratio of bou nd water and the higher molecular mobility of mobile water. The T-mc of the formulation containing PVP was higher than that expected from the higher T -2 values of water because of the lower molecular mobility of mobile water regardless of the higher ratio of mobile water. The T-mc of these lyophiliz ed formulations was higher than their T-g by 23 degrees C to 34 degrees C, indicating that the formulations became a NMR-detected microscopically liqu idized state below their T-g. Conclusions. The quantity and the molecular mobility of mobile water in lyo philized formulations can be considered to affect the T-mc of lyophilized f ormulations, which in turn governs their stability.