RACEMIZATION AND HYDROLYSIS OF TROPIC ACID ALKALOIDS IN THE PRESENCE OF CYCLODEXTRINS

Because of the constantly increasing demand for optically pure drugs i t is of great importance to elucidate factors affecting stereochemistr y, in order to provide a stable formulation with a high chiral quality of the desired isomer. Therefore, the effects of cyclodextrins (CyDs) and their alkylated and hydroxyalkylated derivatives on racemization and hydrolysis of (-)-(S)-hyoscyamine and (-)-(S)-scopolamine were exa mined kinetically and spectroscopically (NMR). Direct methods, based o n a chiral and achiral chromatographic phase system, were used to dete rmine their degradation products and enantiomer composition during sta bility tests. All different CyDs, except alpha-CyD, retarded racemizat ion and hydrolysis. The inclusion of the drug substances in CyDs inhib its the attack of-hydroxyl ions and/or water molecules and thus retard s the racemization and hydrolysis. The racemization of the tropic acid alkaloids is dependent on the pH and temperature. NMR studies were us ed to evidence the formation of a soluble 1:1 complex in aqueous solut ion.