High-Precision Absolute (True) Density Measurements on Hygroscopic Powders by Gas Pycnometry: Application to Determining Effects of Formulation and Process on Free Volume of Lyophilized Products

Density dependent mechanical properties and structures of a freeze dried biopharmaceutical excipient – Sucrose

“…The elastic modulus for FD amorphous sucrose at zero porosity was extrapolated to be 0.78 GPa. True density determined for amorphous sucrose was 1.5162 g/cm 3 at 19 ± 1°C compared to previously reported literature value of 1.506 g cm À3 [45]. The elastic modulus for solid state sucrose available in the literature is for sucrose 5 GPa [46], 2.2 GPa [47] and 32.3 GPa [48].…”

Structural and thermodynamic aspects of plasticization and antiplasticization in glassy encapsulation and biostabilization matrices

“…The specific volume of glassy matrices can be determined by gas pycnometry [47], and relative changes as function of the temperature and pressure by dedicated pressure-volume-temperature (PVT) equipment [46,48,51,58], provided that the samples do not contain any closed porosity. While gas pycnometry is intrinsically less accurate than specific volume techniques for solutions [79,80], relevant specific volume differences in the glassy state can still determined with sufficient precision [48,81]. A technique, by which quantitative information on a specific structural feature of condensed matter can be obtained, namely the sizes of the free volume holes occurring between the molecules constituting the matrix, is PALS (Appendix 1).…”

Characterization of dynamics in complex lyophilized formulations: II. Analysis of density variations in terms of glass dynamics and comparisons with global mobility, fast dynamics, and Positron Annihilation Lifetime Spectroscopy (PALS)

“…In principle, the density of an amorphous solid also reflects free volume, and with high precision density measurements [19], trends in free volume can be studied. For example, it was shown that annealing formulations below their glass transition temperature for times on the order of 1 or 2 days can result in small yet significant increases in density values compared to non-annealed samples [19].…”