Epimerization and Racemization of Some Chiral Drugs in the Presence of Cyclodextrin and Liposomes

Abstract

The effects of a-, β-, y- and dimethyl- β-cyclodextrins (a-, β-, y- and DM-/LCyDs) and liposomes on epimerization or racemization of etoposide, ethiazide and carbenicillin were examined kinetically. a- and β-CyDs accelerated both epimerization and hydrolysis of carbenicillin. They had no effect on epimerization of etoposide, and did not affect racemization and hydrolysis of ethiazide. DM-β-CyD retarded epimerization of etoposide, hydrolysis of picroetoposide (which is an epimer of etoposide), and racemization and hydrolysis of ethiazide, but had no effect on epimerization and hydrolysis of carbenicillin. y-CyD retarded epimerization of etoposide and hydrolysis of picroetoposide. On the other hand, y-CyD accelerated epimerization of carbenicillin. It is suggested that the formation of inclusion complexes between CyDs and etoposide, picroetoposide and ethiazide inhibited the attack of bases such as OH-and buffer components, thereby retarding epimerization, racemization and hydrolysis. On the other hand, a-, β- and y-CyDs increased the reactivity of carbenicillin through the OH group, accelerating its epimerization and hydrolysis. Liposomes retarded epimerization of etoposide, hydrolysis of picroetoposide and racemization of ethiazide. Liposomes did not affect epimerization and hydrolysis of carbenicillin. These differences in the effect of liposomes on reactivity may be interpreted in terms of the solubility of the drugs. © 1989, The Pharmaceutical Society of Japan. All rights reserved.