Document Type : Original Article
Authors
1
Department of pharmaceutics, Faculty of pharmacy, Damanhour university, Damanhour, Egypt
2
Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
3
Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
Abstract
Carvedilol has poor oral bioavailability which is attributed to its limited aqueous solubility, intestinal efflux, and pre-systemic hepatic metabolism. This work aimed to increase carvedilol bioavailability via a self-emulsifying drug delivery system (SEDDS). Liquid-SEDDS were initially prepared and the best formula with the highest drug release was converted into powder form to improve stability. A ternary phase diagram was performed using various ratios of Olive oil, Tween 80, and Propylene Glycol (as oil, surfactant, and co-solvent, respectively) to obtain 21 formulations. All formulations were characterized by visual inspection, accelerated aging, emulsification time and precipitation assessment, and in vitro drug dissolution studies. The best SEDDS formula was adsorbed onto a carrier to be transformed into solid powder, Fumed Silica, Avicel PH101, and their combinations, to obtain solid-SEDDS. Drug dissolution, DSC, and ray diffraction were performed to formula showing the best flow properties. All SEDDS showed enhanced drug dissolution relative to the pure drug, with high initial drug release. Formula F14 showed a prompt drug of about 92% within 5 minutes with a percentage dissolution efficiency of 93% after ten minutes. Formulas prepared using Avicel PH101 showed the best flow properties and were used for further investigations. Drug dissolution parameters were best from solid-SEDDS using Avicel PH101 alone. For DSC and X-ray diffraction studies, the drug characteristic peaks disappeared indicating a reduction in drug crystallinity. Solid-SEDDS could enhance the Carvedilol dissolution rate with subsequent improved oral bioavailability by decreasing its pre-systemic metabolism.
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