Computational analysis of dual targeting of β1-adrenergic and AT1 receptors by bisoprolol fumarate and candesartan cilexetil for hypertensive modulation.

Abstract

This study explores a dual-action approach for hypertension management based on a co-formulated suspension containing Candesartan cilexetil (CC) - Bisoprolol fumarate (BF) system, combining FTIR characterisation with computational modelling to evaluate molecular compatibility, binding behaviour, and pharmacokinetic properties.Direct in situ FTIR-ATR spectral analysis confirmed the successful interfacial wetting and co-dispersion of both drugs within the surfactant matrix, driven by robust hydrophobic interactions and cooperative hydrogen bonding. Hirshfeld surface analysis revealed complementary intermolecular interaction patterns between BF and CC, with BF exhibiting flexible hydrogen-bond networks and CC showing directional hydrogen bonding, π-π stacking, and electrostatic interactions.These distinct yet complementary profiles suggest favourable molecular packing and potential co-formulation. Molecular docking further demonstrated balanced binding of the dual system to both β1 and AT1 receptors, with binding energies of -5.19 and -4.88 kcal/mol, respectively. Furthermore, ADMET results indicate poor gastrointestinal absorption and low oral bioavailability, mainly due to high lipophilicity, which may limit in vivo efficacy, although the compound shows an overall acceptable safety profile.In summary, while the CC-BF system appears promising as a dual-target antihypertensive strategy, further formulation improvements and experimental in vitro and in vivo validation are required to confirm its therapeutic potential.