New oral dosage form for elderly patients. III. Stability of trichlormethiazide in silk fibroin gel and various sugar solutions

The hydrolysis of trichlormethiazide (TCM) in silk fibroin gel (SFG) prepar ed in various sugar solutions (such as ribose, fructose, mannose, and gluco se solutions) was determined. The hydrolysis rate of TCM differed with the variety of sugars utilized in this study; that is, it decreased in the foll owing order: ribose > fructose > mannose > glucose. To investigate the rela tionship between the hydrolysis rate of TCM and the physicochemical propert ies of the sugar molecule, the amount of unfrozen water of sugar molecules was calculated from differential scanning calorimetry (DSC). The amount of unfrozen water increased with an increase in the number of the equatorial O H groups n(e-OH) per sugar molecule that are able to hydrate favorably to t he surrounding water molecules. The hydrolysis rate constant decreased with increase in n(e-OH); glucose, having a large n(e-OH) in this study could e ffectively stabilize TCM.