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
  Yoshioka S.  Aso Y.  Nakai Y.  Kojima S.
  National Institute of Health Sciences, Tokyo, Japan.
  Effect of high molecular mobility of
  poly(vinyl alcohol) on protein stability of lyophilized gamma-globulin
  Journal of Pharmaceutical Sciences.  87(2):147-51, 1998 Feb.
  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.

  Hancock BC.  Shamblin SL.  Zografi G.
  School of Pharmacy, University of Wisconsin-Madison 53706, USA.
  Molecular mobility of amorphous
  pharmaceutical solids below their glass transition temperatures.
  Pharmaceutical Research.  12(6):799-806, 1995 Jun.
  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'.

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