Fabrication of cardiovascular drug combination as Bilayer tablets: A Strategy for 24-Hour Hypertension Management

Combination antihypertensive drug therapy is frequently recommended for patients with cardiovascular disorders. A persistent issue with current therapies is morning hypertension, as the therapeutic effect of the drugs does not extend for 24 h, necessitating repeated dosing. A bilayer tablet comprising Olmesartan medoxomil and Azelnidipine was developed to facilitate a rapid onset of action through the immediate release of an Olmesartan medoxomil inclusion complex and a floating sustained release of Azelnidipine. In this study, an OLM: HP βcd (1:2) inclusion complex was utilized alongside various superdisintegrants, namely sodium starch glycolate, croscarmellose sodium, and crospovidone, to ensure rapid disintegration of the immediate-release dose. Polyethylene oxide (PEO) WSR 303 was employed as a sustained-release hydrophilic polymer, in conjunction with potassium bicarbonate as a gas-generating agent for the floating layer. Design Expert software was used to formulate and evaluate the various batches. The in vitro drug release profile demonstrated the immediate disintegration of the OLM layer within 5 min, with a lag time of 45 s for the floating layer following the disintegration of the immediate-release layer. The floating layer exhibited in vitro and in vivo buoyancy for 8-10 hours. An in vivo pharmacokinetic study in rabbits indicated enhanced bioavailability of these drugs through the maintenance of steady-state plasma concentrations compared with conventional tablets. Based on the observed results, it can be concluded that floating bilayer tablets can enhance the bioavailability of the formulated antihypertensive drugs. Furthermore, the novel bilayer tablet design approach could provide consistent drug release over a 24-hour period.