Drug release profiles of Atenolol and Benidipine from pH-responsive polymeric hydrogel matrix

Due to the limitations such as short biological half-life and extensive hepatic first-pass metabolism causing fluctuations in drug concentration in plasma, prolonged time dosing frequency following a single dose, unwanted side effects, age-dependent personal risks (i.e., forgetfulness to use drugs regularly on time, or the having to use more than one drug), and consequent poor patient compliance, the design of novel drug carrier systems is of vital importance. In this sense, herein, the potential utilization of a crosslinked free-radical polymerized acrylic acid-based hydrogel system for delivering of two model anti-hypertensive drugs belonging to Beta Blocker [(BB), Atenolol (ATE)] and Calcium Channel Blockers [(CBB), Benidipine (BEN)] was demonstrated. The in vitro release behavior of ATE and BEN from the poly(acrylic acid) (PAA)-based hydrogel system was examined in response to three different conditions mimicking the gastric (SGF, pH of 1.2), intestinal (SIF, pH of 7.4) and physiological body fluids (SPF, pH of 7.4) at 37 °C. Degree of swelling of the respective hydrogels and release kinetics were also compared. As a result, the highest swelling for all PAA-based hydrogel matrixes was observed in SIF (pH 7.4) and a Fickian diffusion mechanism was predominant. The distribution of the loaded drug in the hydrogel matrix was found to be quite uniform, and the PAA-based hydrogels prepared in this work have the potential to act as a suitable drug carrier for the delivery of BB and CCB. Graphical abstract: pH-responsive releasing of beta (β)-adrenergic or calcium antagonists’ drugs from polymeric matrix and their mechanism of action against hypertension [Figure not available: see fulltext.]