Mechanism of glass ampoule breakage prevention during the freeze-drying process of sodium thiopental lyophilization products on addition of sodium chloride

Abstract

Glass ampoule breakage during the freeze-drying process was prevented by the addition of sodium chloride to the formulation of lyophilization products of sodium thiopental. In order to clarify the ampoule breakage prevention mechanism, the physicochemical behavior of the freeze-drying process was monitored by simultaneous XRD-DSC measurements and thermal mechanical analysis (TMA). During the freezing process of formulated solution, the smaller heat of fusion of crystallized ice with the addition of sodium chloride was observed in comparison to that without sodium chloride. Although a greater amorphous portion remained, a higher crystal habit of hexagonal ice was reproducibly observed in the XRD patterns with the addition of sodium chloride during the freezing process. In the measurement of TMA, the scattering of the thermal expansion rate of formulated solution was significantly reduced by the addition of sodium chloride. These observations indicated that the addition of sodium chloride minimized the scattering of the thermal expansion rate and might be a cause for the inhibition of glass ampoule breakage during the freeze-drying process.