X-Message-Number: 13841 Date: Mon, 5 Jun 2000 00:24:06 -0700 (PDT) From: Doug Skrecky <> Subject: molecular mobility and glass transition Citations: 1-2 <1> Authors Yoshioka S. Aso Y. Nakai Y. Kojima S. Institution National Institute of Health Sciences, Tokyo, Japan. Title Effect of high molecular mobility of poly(vinyl alcohol) on protein stability of lyophilized gamma-globulin formulations. Source Journal of Pharmaceutical Sciences. 87(2):147-51, 1998 Feb. Abstract The protein stability of lyophilized serum gamma-globulin (BGG) formulations containing poly(vinyl alcohol) (PVA) and dextran was studied in relation to the molecular mobility as determined by proton NMR. The critical temperature, Tmc, at which the Lorentzian relaxation process due to liquid polymer protons appears in these lyophilized formulations was lower than the glass transition temperature, Tg. Above Tmc, protein aggregation in the formulations was related to the Tmc according to the Williams-Landel-Ferry equation by replacing Tg with Tmc. Protein aggregation appears to occur substantially in a "rubbery-like" state even below Tg, if the formulations become microscopically liquidized above Tmc. Lyophilized BGG formulations containing PVA with a lower water content were less stable than those containing dextran with a higher water content. The difference in stability can be explained by the difference in the Tmc of these formulations. Tmc that is determined by NMR relaxation measurement appears to be a useful parameter for the characterization of protein formulations, for which the Tg cannot generally be determined by standard calorimetric techniques. Furthermore, Tmc appears to be more closely related to protein stability than does Tg. <2> Authors Hancock BC. Shamblin SL. Zografi G. Institution School of Pharmacy, University of Wisconsin-Madison 53706, USA. Title Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Source Pharmaceutical Research. 12(6):799-806, 1995 Jun. Abstract PURPOSE. To measure the molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures (Tg), using indomethacin, poly (vinyl pyrrolidone) (PVP) and sucrose as model compounds. METHODS. Differential scanning calorimetry (DSC) was used to measure enthalpic relaxation of the amorphous samples after storage at temperatures 16-47 K below Tg for various time periods. The measured enthalpy changes were used to calculate molecular relaxation time parameters. Analogous changes in specimen dimensions were measured for PVP films using thermomechanical analysis. RESULTS. For all the model materials it was necessary to cool to at least 50 K below the experimental Tg before the molecular motions detected by DSC could be considered to be negligible over the lifetime of a typical pharmaceutical product. In each case the temperature dependence of the molecular motions below Tg was less than that typically reported above Tg and was rapidly changing. CONCLUSIONS. In the temperature range studied the model amorphous solids were in a transition zone between regions of very high molecular mobility above Tg and very low molecular mobility much further below Tg. In general glassy pharmaceutical solids should be expected to experience significant molecular mobility at temperatures up to fifty degrees below their glass transition temperature. Additional note by the poster: Since in dry materials a very small amount of moisture has a dramatic effect at lowering glass transition, this temperature is quite non-uniform at the microscopic level. Bulk Tg' thus can be much higher than local microscopic Tg'. This is much less of a confounding factor in moist products, that are frozen. Molecular mobility here apparently is halted close to bulk Tg'. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=13841