The physical state of solutes in frozen and freeze dried systems

The phase behavior of glycine during freezing and freeze drying was studied as a function of the glycine salt form, pH, and ionic strength. Glycine hydrochloride and sodium glycinate solutions adjusted to pH 7 crystallized slowly from frozen solution, forming a mixture of the $\beta$ and $\gamma$-polymorphs of neutral glycine. Neutral glycine and sodium chloride mixtures crystallized slowly from frozen solutions forming a mixture of the $\beta$ and $\gamma$ polymorphs. The data suggest that adding sodium chloride to a neutral glycine solution slows the rate of crystallization which favors the formation of the $\gamma$-polymorph over the $\beta$-polymorph. Glycine hydrochloride was used as a model compound to study the kinetics of solute crystallization from 'frozen' solution. Glycine hydrochloride undergoes crystallization from the 'frozen' solution relatively slowly when annealed. The crystallization of glycine hydrochloride proceeds via a Prout-Tompkin's model, indicating crystal growth from nuclei formed during the freezing process. The temperature dependence of the crystallization rate in the temperature range between $-37\sp\circ$C to $-70\sp\circ$C follows Arrhenius kinetics, as opposed to William-Landel-Ferry kinetics. The state behavior of lyotropic liquid crystals was studied using nafcillin sodium and methylprednisolone sodium succinate as model solutes. Concentrated solutions of both solutes showed birefringent textures when observed through crossed-polarized light, indicating the formation of lyotropic liquid crystals. Differential scanning calorimetry (DSC) thermograms of nafcillin sodium and methylprednisolone sodium succinate solutions contained endotherms at $-5.5\sp\circ$C and $-3.5\sp\circ$C, respectively, corresponding to melting of the liquid crystalline structure. X-ray powder diffractograms (XRD) of freeze-dried nafcillin sodium and methylprednisolone sodium succinate were indicative of smectic type A liquid crystals. The data suggest solutes which form lyotropic liquid crystals in solution may form 'dried' lyotropic liquid crystalline powders when freeze dried. Finally, manometric temperature measurement was evaluated as a non-invasive method of monitoring product temperature during the primary drying phase of lyophilization. The experimental transient pressure response data were fitted to a mathematical equation which described the transient pressure response and the calculated manometric temperature compared to thermocouple measurements. Manometrically measured temperatures were consistently lower than the thermocouple measurements, as would be expected from the temperature gradient across the cake.