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KMID : 0369820160460020153
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Jorunal of Korean Pharmaceutical Sciences
2016 Volume.46 No. 2 p.153 ~ p.168
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Design, optimization, and evaluation of ezetimibe solid supersaturatable self-nanoemulsifying drug delivery for enhanced solubility and dissolution
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Dash Rajendra Narayan
Mohammed Habibuddin
Humaira Touseef
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Abstract
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This study was intended to develop a solid supersaturatable self-nanoemulsifying drug-delivery system (solid S-SNEDDS) to improve the solubility and dissolution of a poorly water-soluble drug ezetimibe. Self-nanoemulsifying drug delivery system (SNEDDS) preconcentrate was systematically optimized by a central composite design (α = 1.682). The optimized SNEDDS preconcentrate consisted of Captex 355 (30 % w/w), Cremophor RH40 (40 % w/w) and Imwitor 988 (30 % w/w). Saturation solubility of ezetimibe in the optimized SNEDDS preconcentrate was found to be 90.62 mg/ml. HPMC-E5 (5 % w/w) and ezetimibe (90 % saturation solubility level) were added to the SNEDDS preconcentrate to form a supersaturatable SNEDDS (liquid S-SNEDDS). Dilution of liquid S-SNEDDS resulted in a nanoemulsion having a mean droplet size of 27.3 nm. TEM studies of diluted liquid S-SNEDDS confirmed uniform shape and size of the droplets. The liquid formulation was adsorbed onto microcrystalline cellulose and talc to form a solid S-SNEDDS. In vitro supersaturation test of solid S-SNEDDS showed a higher ezetimibe concentration (that retarded precipitation of ezetimibe at least up to 60 min) in comparison to the solid-SNEDDS (without HPMC-E5). PXRD studies of the precipitates collected from the in vitro supersaturation test, revealed the presence of amorphous ezetimibe. DSC and SEM results indicated that the presence of ezetimibe in an amorphous and molecular dispersed state within the solid S-SNEDDS. In vitro release (in 15 min) of ezetimibe from solid S-SNEDDS improved by 1.17, 1.69, and 13.21-fold as compared with solid-SNEDDS, commercial product, and the free drug (powder), respectively.
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KEYWORD
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Central composite design, Solid S-SNEDDS, Supersaturation, Solubility enhancement, Dissolution enhancement
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