Propranolol resolution using enantioselective biphasic systems

Abstract

Abstract The commercialization of chiral drugs is an increasing concern in the pharmacological field since the differences in the pharmacological activities of enantiomers may result in serious problems in the treatment of diseases using racemates. The resolution of chiral drugs is important for the development of safer and more active pharmaceuticals. This work aims to develop an enantioseparation platform for the resolution of propranolol (R/S-PRP) resorting to esters of tartaric acid and chiral ionic liquids (CILs) as chiral selectors in biphasic systems. More specifically, the efficiency of enantioselective liquid–liquid extraction (ELLE) systems, both aqueous and non-aqueous biphasic systems, are here studied, aiming to do a direct comparison between these two types of systems for the resolution of R/S-PRP. Studies were carried to evaluate the proper phase forming components of ELLE, R/S-PRP:chiral selector ratio, the potential of CILs over esters of tartaric acid, and the most suitable alkyl chain length for the esters of tartaric acid. It was found that the selected organic phase formers of ELLE, 1,2-dichloroethane and ethyl acetate, greatly impact the potential of the enantiorecognition of the system. The most efficient biphasic system identified was composed of 1,2-dichloroethane-water, and dipentyl-L-tartrate and boric acid as chiral selectors, with a enantioselectivity of 2.54. This system was further employed for the resolution of R/S-PRP in centrifugal partition chromatography, to assess its scalability potential, being shown that it was possible to increase the purity of R-PRP from 59% to 75%.