MK-0591, a potent indirect leukotriene biosynthesis inhibitor, is poorly absorbed when administered orally as a crystalline sodium salt, primarily because of its low aqueous solubility (5 mu g/mL). However, the lyophilized X-ray amorphous form with much higher aqueous solubility is very well absorbed and physically stable for long time periods. To better understand the physical stability of the amorphous state, conditions at which the compound will crystallize from the amorphous state were investigated in the context of its glass transition temperature. The physical stability of X-ray amorphous MK-0591 was evaluated by DSC with enhanced sensitivity using the crystallization exotherm at ca. 185 degrees C (10 degrees C/min) to detect crystallization in the solid matrix. No crystal formation was observed at 30 degrees C for 6 months, 60 degrees C for 6 months or 30 degrees C at 75% RH for 6 months. This prolonged physical stability was attributable to two factors : its high glass transition temperature (ca. 125 degrees C) and liquid crystal formation in aqueous solutions at concentrations greater than 60 mg/mL. Crystallization could not be induced after isothermally holding the X-ray amorphous MK-0591 at 120 degrees C for 17 h. Seeding with crystalline MK-0591 (10%) also failed to induce crystallization at 50 degrees C for 6 months or at 30 degrees C at 75% RH for 6 months. Water plasticizes lyophilized MK-0591, lowering the T-g and inducing the onset of crystallization to 100 degrees C. Crystallization at room temperature does not occur with equilibration at high relative humidites probably because of the additional stability imparted to the system by the formation of a lyotropic liquid crystalline phase. The behaviour of amorphous MK-0591, with its high T-g in the solid state and its liquid crystalline properties in concentrated aqueous solution, provided sufficient physical stability to permit its use in oral formulations.