Subnanometre size free volumes in amorphous Verapamil hydrochloride: A positron lifetime and PVT study through Tg in comparison with dielectric relaxation spectroscopy

Positron annihilation lifetime spectroscopy (PALS), a method well established for the study of polymers, is employed to characterize the temperature dependence of the free volume through Tg in the amorphous pharmaceutical Verapamil hydrochloride. From the PALS spectra analyzed with the routine LifeTime9.0 the size (volume) distribution of local free volumes (subnanometre-size holes), its mean, 〈vh〉〈vh〉, and mean dispersion, σh, were calculated. A comparison with the macroscopic volume from PVT-experiments delivered the hole density and the hole free volume fraction and in that way a complete characterization of the free volume microstructure. These data are used in correlation with structural (α-) relaxation data from broad-band dielectric spectroscopy in terms of the Cohen–Turnbull free volume model. An extension of this model, distinctions in the free volume behaviour of the glassy and supercooled-liquid state and different ways of extrapolating the equilibrium part of the free volume into the temperature range of the glass are discussed. The potential of the PALS method for the study of pharmaceuticals is briefly reviewed and some recently developed applications (analysis of density fluctuations) are illuminated.