The effect of dihydroxypropyl theophylline on the solubility and stability of menadione (vitamin K3).

The effect of dihydroxypropyl theophylline on the solubility and stability of menadione was investigated. An increase of about 4-fold in the solubility of menadione with 0.1 m dihydroxypropyl theophylline was observed at 30 degrees C. Thermodynamic paremeters were calculated by conducting the experiments at different temperatures. The rate of base-catalyzed degradation of menadione in the presence and absence of dihydroxypropyl theophylline was found to be first order with respect to the vitamin at all conditions of pH, temperature and concentration. Dihydroxypropyl theophylline leads to an accelerated rate of decomposition of the drug at relatively high pH values. This adverse effect decreases considerably as the pH of the solution approaches neutrality. At pH = 7.5, dihydroxypropyl theophylline exerts a rather stabilizing effect on menadione solution. The enhancement of the rate of base-catalyzed degradation is directly proportional to the concentration of dehydroxypropyl theophylline at pH = 9.2. The base-catalyzed degradation of menadione in the absence and presence of dihydroxypropyl theophylline follows Arrhenius' equation for the thermal activation of molecules. No noticeable variation in the energy of activation of both systems was detected. The addition of 4% dihydroxypropyl theophylline to menadione solution nearly completely suppressed the aerobic photodegradation of menadione.