Stability of Atenolol, Acebutolol and Propranolol in Acidic Environment Depending on its Diversified Polarity

Abstract

The main objective of this research was to investigate the relationship between the polarity of atenolol, acebutolol, and propranolol described by logP and kinetic and thermodynamic parameters characterizing their degradation process in acidic solution. Hydrolysis was carried out in hydrochloric acid at molal concentrations of 0.1 mol/L, 0.5 mol/L, and 1 mol/L for 2 hr at 40°C, 60°C, and 90°C. Chromatographic-densitometric method was used for the determination of drugs under investigation. The identification of degradation products was carried out by using ¹H NMR. The degradation processes that occurred in drugs under investigation are described with kinetic parameters (k, t_0.1, and t_0.5) and energy of activation (E_a). It has been found that the stability of drugs increases toward lipophilic propranolol in the assumed experimental model. The rate constants k decrease, contrary to t_0.1, t_0.5, and E_a, which vary comparably to logP, thus increasing from the most hydrophilic atenolol, through acebutolol, of lower polarity, to the most lipophilic propranolol. This study demonstrated that the stability of chosen beta-adrenergic blocking agents increases with their lipophilicity.

Keywords:

• beta-blockers' stability
• kinetics of degradation process
• TLC
• drug analysis
• atenolol
• acebutolol
• propranolol