Glassy state of pharmaceuticals. III. Thermal properties and stability of glassy pharmaceuticals and their binary glass systems.

Glassy pharmaceuticals were prepared by cooling the melts and their state was confirmed by measuring the glass transition temperature (Tg) and the anomalous endothermic peak (heat capacity maximum) in the differential scanning calorimetry (DSC) curves. Glass formation was found for 20 pharmaceuticals (aspirin, phenobarbital, antipyrine and so on). The values of the ratio of Tg and melting temperature (Tm) of these pharmaceuticals lay between 0.59 and 0.84. Although the glassy indomethacin was very stable, remaining as a glass for 2 years at room temperature, glassy phenobarbital with the same Tg as glassy indomethacin was unstable, and devitrification occurred within a week. Thus the rate of crystallization of pulverized glassy phenobarbital was determined by the X-ray diffraction method. The crystallization of pulverized glassy phenobarbital proceeded rapidly and the degree of crystallinity reached a maximum of 75% after 24 h.Crystallization of glassy salicin was followed by means of DSC curves. It was revealed that stabilization by enthalpy relaxation occurred simultaneously with the crystallization in glassy salicin during standing.Binary glass systems of pharmaceuticals were prepared with the aim of improving the stability of the glass, and several thermal properties of binary glass systems were investigated.