Formulation, characterization and optimization of nebivolol-loaded sustained release lipospheres

Abstract

Purpose: To formulate, characterize and optimize nebivolol-loaded sustained release lipospheres (LPs) using beeswax (BW) as the drug carrier. Methods: Nebivolol-loaded LPs were formulated using solvent evaporation technique (SET) and characterized. The impact of independent variables on responses such as percentage yield (PY), entrapment efficiency (EE) and drug release after 12 h (DR12) was assessed using central composite design (CCD). Numerical and graphical optimization techniques were also used to evaluate outcomes of the measured responses. Results: Twenty micron-sized (20-100 µm), smooth spherical LPs with good rheological properties were produced. The yield ranged from 33 (F10) to 81 % (F6), while EE ranged from 32 (F4 and F9) to 69 % (F6). The results of rheological evaluation revealed angle of repose > 24 o, Hausner's ratio > 1.5, and Carr's index ranging from 13 to 19 %. Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and x-ray diffraction (XRD) revealed nebivolol and BW compatibility, and the absence of possible interactions between formulation components. Duration of nebivolol release was strongly associated with BW concentration and formulation F15 showed minimum drug release (46 %). Drug release was significantly higher in formulations with similar BW concentrations and low Tween-20 (T-20) concentrations (F1 and F11) than in formulations with high T-20 concentrations (F2, p < 0.05). The zeta potential of deflocculated LPs ranged from +15 to +35 mV. Nebivolol release (46-85 %) at pH 6.8 was significantly affected by BW concentration and it followed zero order model. Conclusion: The results obtained in this study have shown that BW is a suitable material for producing an effective sustained release formulation. The mechanism of drug release in nebivolol-loaded LPs is diffusion accompanied by erosion.

Lipospheres and Pro-Nanolipospheres: Advancements in Drug Delivery Systems

“…Moreover, lipospheres were used to encapsulate antibiotics such as Ceftriaxone, a third-generation cephalosporin (Attama et al, 2009) and Gentamicin which is active against a variable range of grampositive and gram-negative bacteria (Momoh & Esimone, 2012) Some anti-hyperlipidemic drugs such as Fenofibrate were formulated also as lipospheres which showed a superior lowering of serum cholesterol levels when compared with the marketed product (Saroja & Lakshmi, 2013). Nebivolol (NEB) is another antihypertensive drug of poor bioavailability that was encapsulated into liposphere by Hanif et al (Hanif et al, 2019) and then further research was done by combining NEB with Ivabradine (IVB) and co-loading into lipospheres which produced a prolonged release formulation with improved bioavailability when compared to the marketed oral tablets (Hanif et al, 2021). More research was done by Maheen and Rasul using the antihypertensive drug enalapril maleatean ACE inhibitor-that was formulated as liposphere and showed a sustained-release pattern that led to a maximum benefit of controlling blood pressure with the least side effects and cost for hypertensive patients .…”