Stability studies on drugs are very important as they allow a better understanding of their physico-chemical, parmacotherapeutic and toxicological behavior. The group of 1,4-benzodiazepines is vastly used in the treatment of different nervous diseases such as anxiety, insomnia and epileptic convulsions because of the wide variety of their properties attributed to the complicated benzodiazepinic structure. Due to the therapeutic interest that these compounds present, research on their chemical stability as well as determination in pharmaceutical preparations and biological samples is an obligation.
1,4-benzodiazepines undergo hydrolysis in acidic aqueous solutions which may be very important for their absorption in the gastrointestinal tract. Owing to the importance of the mechanism of this reaction, degradation kinetics of such drugs has been studied by many authors. Even though there is a general scheme of their hydrolysis, the reaction is complicated and in many cases the results are vague and not conclusive. Several members of this group, although similar in stucture, are stongly different in their acidic hydrolysis kinetics. They form long-or short-lived intermediates, they show monophasic or biphasic kinetics.
In this talk, the general scheme of degradation of 1,4-benzodiazepines will be presented. Specific mechanisms along with kinetic parameters of acidic hydrolysis of several compounds that belong to this category will be also discussed. Our research work on this topic will be included, as well.
Speaker: H. A. Archontaki, University of Athens
Time: Monday, 12 October 1998, 10:00