Solid lipid nanoparticles as new strategy for oral delivery of nebivolol hydrochloride

Nebivolol Hydrochloride (Neb), a third-generation β-blocker, is commonly used in the treatment of hypertension, but suffers from low oral bioavailability due to its poor aqueous solubility. Solid lipid nanoparticles (SLNs) have emerged as a promising strategy to enhance drug solubility and control the release rate, offering several advantages over other nanocarriers, including increased drug loading of lipophilic drugs and safety. This work focused on the optimization and characterization of Neb-loaded SLNs, using Compritol® 888 ATO, as the solid lipid excipient and Octadecylamine, as stabilizer. The SLNs were prepared using the Hot High Shear Homogenization method, a solvent-free and green technique, in which the drug dispersion and homogenization occur at temperatures above the lipid melting point. Pluronic® F68 was added as surfactant to improve the formulation stability. Optimization of the SLNs formulation was achieved through the Design of Experiments (DoE), evaluating eight different factors involved in the formulation process: weight of Pluronic® F68 (Plur), weight of Compritol ® 888 ATO (Comp), weight of Octadecylamine (Oct), Ultra-Turrax (UT) speed (rpm), homogenization time, amplitude (Amp) of the sonicator, sonicator pulse mode (Pul) and sonication time. The optimized SLNs exhibited a particle size (Z-Av) of (292.8 ± 89.7) nm, a polydispersity index (PDI) of 0.266 ± 0.075, and a Zeta potential (ZP) of (61.7 ± 1.9) mV. Drug entrapment efficiency (EE%) reached approximately 70% and a controlled release profile was obtained. The formulations remained stable at both room temperature and 4°C for one week. Morphologically, the SLNs maintained a spherical shape as observed by Scanning Electron Microscopy (SEM). Further characterization through Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) was performed. Viability tests on AGS cells revealed no significant toxicity, supporting the biocompatibility of the formulation. All these findings demonstrated the potential of this optimized SLN formulation as an effective and safe strategy for oral delivery of Nebivolol Hydrochloride in hypertension treatment.