Novel enantioselective synthesis and dissolution studies on enteric coated pellets of (S)-duloxetine hydrochloride

Abstract

The enantioselective hydrogenation of 2-bromo-1-(thiophen-2-yl)ethanone and further elaboration of the cyclic carbamate derived from γ-aminoalcohol to provide a facile synthesis of (S)-duloxetine, a potent dual inhibitor of serotonin and norepinephrine reuptake, is described. Enteric coated pellets with polymer load of 25% and 30% failed to provide the required acid resistance of the pellets. Very insignificant amount of drug was leached from the coated tablets with polymer load 35% and 40% in the acidic phase, whereas almost the whole amount of drug was released in the buffer phase. The results generated in this study showed that the proper selection of polymeric materials based on their physicochemical properties, as well as the polymer load is important in designing delayed release pellets dosage form with acceptable dissolution profile. © 2013 Bulgarian Academy of Sciences, Union of Chemists in Bulgaria.