Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Muhammad Hanif¹, Hafeez U Khan^1,2 , Samina Afzal¹, Abdul Majeed¹, Nabila Iqbal², Khurram Afzal³, Mehwish Andleeb⁴, Aisha Rauf⁵, Athar Farooq¹

¹Faculty of Pharmacy, Bahauddin Zakariya University, Multan; ²Faculty of Pharmacy, University of Sargodha, Sargodha; ³Department of Food Sciences, Bahauddin Zakariya University, Multan; ⁴Faculty of Pharmacy and Alternative Medicines, Islamia University, Bahawalpur; ⁵Institute of Pharmaceutical Sciences, Quaid-e-Azam University, Islamabad, Pakistan.

For correspondence:- Hafeez Khan Email: qarani_pharmacist@yahoo.com Tel:+923368658751

Accepted: 11 January 2019 Published: 28 February 2019

Citation: Hanif M, Khan HU, Afzal S, Majeed A, Iqbal N, Afzal K, et al. Formulation, characterization and optimization of nebivolol-loaded sustained release lipospheres. Trop J Pharm Res 2019; 18(2):223-231 doi: 10.4314/tjpr.v18i2.2

© 2019 The authors.
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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.

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