Stabilization of Local Anesthetics in Liposomes

Abstract

The first-order hydrolysis rate constants of local anesthetic drugs have been measured in aqueous buffer solution, k_B, and in liposomes, k_obs, at pH 12.2 and 30°C. Also, the fraction of drug associated with the lipid phase, f_L, and the partition coefficient between the aqueous and lipid phase, Kg, were determined. The stability of benzocaine was measured in several liposome compositions, and as a function of benzocaine concentration, phospholipid concentration, and ionic strength of the medium. Values of the rate constant in the lipid phase, k_L, were estimated from a simple kinetic model and predictions of the relative contributions of k_L and k_B to k_obc were made. Different methods of liposome preparation, and the stabilities of local anesthetics in liposomal and micellar systems were compared.