2001 Volume 49 Issue 12 Pages 1526-1530
Anhydrous theophylline was prepared by heating theophylline monohydrate at temperatures between 60 °C and 140 °C. The effects of dehydration temperatures on the moisture absorption and dissolution behavior of anhydrous theophylline were investigated in this study. The hydration rate of anhydrous theophylline at 95% relative humidity and 25 °C decreased with increasing dehydration temperatures. From the fitting analysis of solid-state reaction models, the hydration reaction was found to be governed by the phase boundary reaction model for samples prepared at lower dehydration temperatures (<100 °C) but the reaction obeyed the growth of nuclei reaction model when samples were dehydrated at higher temperatures. The dissolution rates of various anhydrous theophylline samples were measured by the rotating disk method. The calculated solubility of anhydrous theophylline prepared by heating was about 2.5 times higher than that of theophylline monohydrate. The phase transformation rate from the anhydrous form to the monohydrate during dissolution tests decreased with higher dehydration temperatures. It was found that the anhydrous theophylline prepared at different dehydration temperatures transformed to the monohydrate by way of different growth of hydrate nuclei mechanism.
