pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

ABSTRACT

Propranolol HC1, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15% were added to the matrices prepared by hydroxypropyl methylcellulose [HPMC] and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time [MDT] as well as similarity factor [f[2]] were calculated for all formulations. It was found that incorporation of 5 and 10% tartaric acid in tablet formulations with 30% HPMC resulted in a suitable pH-independent release profiles with significant higher f[2] values [89.9 and 87.6 respectively] compared to acid free tablet [58.03]. The other two acids did not show the desirable effects. It seems that lower pK[a] of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles