A simple but novel mixed surfactant system was designed to fabricate a self-nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic-lipophilic balance (HLB) value. The impacts of HLB and molecular structure of surfactants on the formation of SNEDDS were investigated. After screening various oils and surfactants, nifedipine (NDP)-loaded liquid SNEDDS was formulated with Imwitor(®) 742 as oil and Tween(®)/Span(®) or Cremophor(®)/Span(®) as mixed surfactant. Droplet size of the emulsions obtained after dispersing SNEDDS containing Tween(®)/Span(®) in aqueous medium was independent of the HLB of a mixed surfactant. The use of the Cremophor(®)/Span(®) blend gave nanosized emulsion at higher HLB. The structure of the surfactant was found to influence the emulsion droplet size. Solid SNEDDS was then prepared by adsorbing NDP-loaded liquid SNEDDS comprising Cremophor(®) RH40/Span(®) 80 onto Aerosil(®) 200 or Aerosil(®) R972 as inert solid carrier. Solid SNEDDS formulations using higher amounts (30-50% w/w) of Aerosil(®) 200 exhibited good flow properties with smooth surface and preserved the self-emulsifying properties of liquid SNEDDS. Differential scanning calorimetry and X-ray diffraction studies of solid SNEDDS revealed the transformation of the crystalline structure of NDP due to its molecular dispersion state. In vitro dissolution study demonstrated higher dissolution of NDP from solid SNEDDS compared with NDP powder.
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