Stereoselective adsorption and trans-membrane transfer of propranolol enantiomers using cellulose derivatives

Cellulose tris(phenyl carbamate), cellulose tris(3,5-dimethylphenyl carbamate) and cellulose tris(3,5-dichlorophenyl-carbamate), which are known for their ability to resolve enantiomers when used as chromatographic stationary phases, were examined in terms of their ability to adsorb differentially the enantiomers of propranolol hydrochloride and consequent differential transfer when used as excipients in aqueous donor vehicles. Over a range of conditions investigated, optimum stereospecificity was found at pH 7.4, an incubation temperature of 32 degrees C and propranolol concentration of 1 mgml(-1) with 1 mg adsorbent. The ratios of S/R bound was 1.35, 2.65 and 2.31, respectively. The permeation rates of propranolol enantiomers were determined through Silastic membrane in the presence and absence of vehicular cellulose tris(3,5-dimethylphenyl carbamate) and cellulose tris(3,5-dichlorophenyl carbamate). When pure propranolol enantiomers were used, permeation rates of propranolol enantiomers were significantly different, both numerically and statistically (steady-state flux ratios, R/S = 1.70 and 1.68; P = 0.03 and 0.001, respectively). In the absence of adsorbent permeation rates were not significantly different. When racemic propranolol was used, the flux ratios were less, but still of statistical and numerical significance (steady-state flux ratios, R/S 1.14 and 1.14; P = 0.04 and 0.01, respectively) considering the differential activities of propranolol enantiomers. These results demonstrate the potential of enantioselective retardation in transmembrane transfer as an alternative methodology for administering single enantiomers.