Abstract
Nebivolol (NBH) is a third-generation B1-blocker with high selectivity and vasodilation activity. Nevertheless, nebivolol exhibits low oral bioavailability, which may adversely affect its efficacy. Recently, supersaturable self-nanoemulsion (Su-SNE) is an advanced SNE approach that can address low bioavailability The study aims to prepare nebivolol-loaded Su-SNE by reduction the amount of the prepared conventional SNE to half. Besides, an appropriate polymer type and concentration to prevent NBH precipitation upon oral administration have investigated.. A conventional self-nanoemulsion (formula A) was prepared by dissolving NBH in 500 mg vehicle mixture of imwitor®988: cremophor-EL: propylene glycol. Then, eight Su-SNE formulas with the absence or presence of four different polymers were prepared and evaluated. In-vitro precipitation assay was performed to assess the precipitation inhibition capacity of polymers. The ex-vivo permeation through rat intestinal mucosa was also conducted for determination of permeability parameters. Results revealed that (Su-SNA formula SAS1) containing 5% soluplus could effectively retard the nebivolol precipitation. There was no statistical difference between formula A and SAS1; both maintained a higher apparent NBH concentration for approximately 240 min in 0.1N HCl. The permeation rate of conventional (formula A) and soluplus-based Su-SNE (formula SAS1) was significantly improved, and the permeation enhancement ratio was found 2.7 and 3.2, respectively, as compared with non-formulated NBH. Consequently, it is concluded that developing soluplus-based nebivolol SNE is a promising alternative approach. It can enhance nebivolol stability and permeability with half the amount of conventional SNE components.
Highlights
Nebivolol (NBH) is a third-generation β1blocker with high selectivity
Different hydrophilic polymers as a precipitation inhibitor were added to formula (SA) to protect the supersaturated state and stabilise the colloidal dispersion
They appeared as opaque homogeneous suspension, which may be attributed to the inability of HPMC and PVP to dissolve in the SNE components
Summary
Nebivolol (NBH) is a third-generation β1blocker with high selectivity. It has vasodilator and oxidative stress reduction effect through promoting endothelium nitric oxide release [1]. It has been prescribed for the management of hypertension and heart failure, preferred for elderly patients and those with other co-morbid conditions like diabetes and peripheral vascular disease [2]. Lipid-based drug delivery system (LBDDS) is another promising formulation approach. SNEDDS refers to a preconcentrate or anhydrous nanoemulsion. It is typically composed of a drug candidate dissolved in a uniform, transparent mixture of oil(s), surfactant(s) and co-surfactant(s). SNEDDS application has limited by a high amount of surfactants which leads to side effects, such as mucosal irritation [9]
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