Design and evaluation of bilayer tablets of fixed dose combinations for management of hypertension

Abstract

quotBackground: Lifestyle diseases like hypertension require multiple drug therapies where in drugs need to be administered in an orderly fashion. The drug regimen often leads to non-compliance. Therapies need more than one drug to be administered working through various mechanisms of action. Therefore various fixed dose combinations have been developed specifically for lifestyle diseases. newline newlineAim: Aim of the present study was to combine frequently co-administered drugs in hypertension (metoprolol succinate and atorvastatin calcium) and pulmonary arterial hypertension (bosentan monohydrate and sildenafil citrate) as fixed dose combination bilayered tablets where in one drug is sustained release and one immediate release thereby reducing dose related side effects, reducing dosing frequency, cost of manufacturing and improving patient compliance. newline newlineMaterials and Methods: Both the bilayered tablets were prepared by direct compression technique. In the combination of Metoprolol succinate and atorvastatin calcium, Kollidon SR was the polymer for controlling the sustained release of metoprolol. In the combination of Bosentan and sildenafil HPMC K4M Premium DC 2 was used as release retardant. The blends of immediate and sustained release were subjected to pre compression parameters like angle of repose, bulk and tapped density, Carr s compressibility and Hausner ratios. The bilayered tablets were evaluated for post-compression characteristics like hardness, weight variation, thickness, friability test, drug content and in vitro dissolution study. Bilayer tablets were optimised using factorial designs using design expert software. The optimised batch was subjected to stability studies as per ICH guidelines. newline newlineResults and Discussion: FTIR and DSC studies revealed no interaction between drug and excipients. The precompression characteristics of the blends showed good flow and packing properties. Post compression characteristics of tablets showed promising results. Design expert software aided to determine the optimum concentration