Factors affecting stability of z-ligustilide in the volatile oil of radix angelicae sinensis and ligusticum chuanxiong and its stability prediction.

The purpose of this investigation is to obtain a suitable vehicle for Z-ligustilide in the volatile oil of Radix Angelicae Sinensis and Ligusticum Chuanxiong in which it is stable enough for the application in pharmaceutics, to investigate its degradation laws, and to predict its shelf-life at 25 degrees C. Factors including temperature, light, pH value, co-solvents and antioxidants can all influence the stability of Z-ligustilide, thereinto antioxidants could markedly improve its stability in aqueous solution by almost 35%. The suitable vehicle for Z-ligustilide contains 1.5% tween-80, 0.3% Vitamin C, and 20% propylene glycol (PG). Furthermore, the degradation rates of Z-ligustilide were found to conform to a rate equation following Weibull probability distribution within a range of degradation ratio, and the equation could be expressed as follow: ln ln (1/1-alpha) = ln k + m ln t. Where alpha is degradation ratio; t is time; m and k are constants relating to the degradation rate. The degradation rate will get greater as the increasing of parameter k. According to the degradation law obtained from the equation, the drug shelf-life (10% of active ingredient degraded, T90) in this vehicle was predicted to be more than 1.77 years at 25 degrees C through Arrehenius equation and accelerating experiments. The present investigation was undertaken to propose a kinetic treatment that may be applicable to any type of degradation of the active ingredient of pharmaceutical formulation, and also could provide a good foundation for the new drug development of Z-ligustilide, especially for injection formulation.