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

Muhammad Hanif
Hafeez U. Khan
Samina Afzal
Abdul Majeed
Nabila Iqbal
Khurram Afzal
Mehwish Andleeb
Aisha Rauf
Athar Farooq


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.

Keywords: Lipospheres, Nebivolol, Beeswax, Formulation, Central composite design