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
Highlights
Hypertension, congestive heart failure (CHF), myocardial infarction (MI), cerebral diseases and nephropathy result in the death of millions of people globally [1]
A drug used as first-line treatment for hypertension, is a selective beta-blocker which induces vasodilatation via the generation of nitric oxide (NO) [4]
Lipospheres with high BW concentrations and low T-20 concentrations formulated at low stirring speed (SS) (F4, F9, F10, F11, F13 and F20) had percentage yield (PY) < 50 %
Summary
Hypertension, congestive heart failure (CHF), myocardial infarction (MI), cerebral diseases and nephropathy result in the death of millions of people globally [1]. The treatment strategies for cardiovascular diseases (CVDs) only serve as mere palliatives [2]. There is increasing demand for sustained delivery. A drug used as first-line treatment for hypertension, is a selective beta-blocker which induces vasodilatation via the generation of nitric oxide (NO) [4]. Nebivolol is highly effective and more generally accepted than other antihypertensive agents, it requires frequent dosing because of its poor solubility, bioavailability (˂ 40 %) and short plasma half-life (2 h) [9, 10].BW is usually used to improve its solubility and bioavailability. The aim of this study was to formulate, characterize and optimize nebivolol-loaded sustained release LS using BW as drug carrier.
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