Freeze-drying and solubility studies.

Abstract

The medium offering the greatest resistance to heat transfer from the freeze-drying shelf to the moving and subliming surface is the space between the flat shelf top and the concave vial bottom. The resistance to heat transfer can be greatly reduced by improving the thermal conductivity of the intervening space. Several heat transfer augmentation devices, including a multilayered corrugated aluminum quilt and a conformable fluid cushion device, which fill this gap are described. The devices are inexpensive and easy to use. Experimental data show that the resistance of the intervening space is reduced appreciably and the drying rate is greatly increased. The fluid cushion device is superior to the aluminum quilt as it reduces the consequences of spillage of solution and provides greater intervial uniformity among the same batch of vials. Drying times obtained in experiments with and without the fluid cushion device are compared here for different sizes and different types of vials. Product evaluation is conducted by measuring the reconstitution time and observing the product under a microscope. The solubilities of two univalent electrolytes, sodium chloride and potassium chloride, have been measured in eight cosolvent-water binary systems. The solubility of both the solutes has been found to be adequately described by the log-linear solubility equation, log S(m) = log S(w) + fσ. The rank order of the desolubilization slopes obtained for the electrolyte solutes is compared with the solubilization of nonelectrolyte solutes. These results indicate that a cosolvent which is most effective in solubilizing a nonelectrolyte is also most effective in desolubilizing an electrolyte. The solubility of oxacillin sodium in methanol-water mixtures has been determined at various temperatures ranging from +21 to -26 degrees centigrade. The data has been fitted to the log-linear relationship as proposed by Yalkowsky et. al. The heat of solution is determined using the van't Hoff equation and was found to be nearly constant at 1.2 Kcal/mole. There appears to be no dependency of the slope of the log S(m) vs. fraction cosolvent plot to the temperature. The data suggests that there is a polymorphic or amorphic transition of oxacillin at -14.5 degrees centigrade.