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) prepared in various sugar solutions (such as ribose, fructose, mannose, and glucose solutions) was determined. The hydrolysis rate of TCM differed with the variety of sugars utilized in this study; that is, it decreased in the following order: ribose > fructose > mannose > glucose. To investigate the relationship between the hydrolysis rate of TCM and the physicochemical properties 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 OH groups n(e-OH) per sugar molecule that are able to hydrate favorably to the 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 effectively stabilize TCM.