Dilution Phenomenon in Mixed Surfactant based Self Micro Emulsifying Formulations Of Ginger Oleoresin: Ex Vivo And In Vivo Performances

Abhinav Garg, Anoop Kumar, Kanchan Kohli

Abstract


Abstract: Aqueous solubilization of Ginger Oleoresin (GO) in pseudo self micro emulsifying carrier and its influence on ex-vivo intestinal permeation and in-vivo performances was investigated. GO pre-concentrates was prepared using surfactants, Tween 80, Tween 20 and/or 1:1 mixture with a co-surfactant propylene glycol at S/Cos ratio 1:1. Aqueous dilutable region of GO in single or mixed surfactant systems was located from ternary phase diagram drawn between ternary components consisted of surfactant/co-surfactant ratio at 1:1, GO and aqueous phase. Various microstructures were characterized across the dilution line using conductometric and rheological method. Three formulations were selected across the dilution line from mixed surfactants phase diagram as microemulsion area was found to be larger in mixed surfactants over single surfactant based ternary system. GO SMEDDS formulations were physically characterized for refractive index, pH, droplet size and stability assessment. The permeability of GO in diluted pre-concentrate was determined across ex vivo rat intestinal method. Two fold enhancement (p<0.01) in intestinal permeability of GO was obtained from SMEDDS formulation  when diluted upto 9.0ml in comparison to under diluted (2 ml) or over-diluted (25 ml) and control formulation (GO in Tween 80). These findings strongly suggested that SMEDDS diluted upto 9ml behave like a pseudo self emulsifying carrier which inherently had microemulsion characteristics (droplet size 122nm). Modulation of intestinal permeability upon dilution was found closely related with dynamics of microemulsion system. Dilution mediated transitions in microstructure of GO SMEDDS was associated with the changes in the orientation of surfactant molecules at the oil-water interface of microstructures during solubilization of GO. In vivo studies revealed that orally administered GO preconcentrate produced 1.6 folds enhancement in oral bioavailability of GO  over control. Present study demonstrates that intestinal permeability and oral bioavailability can be modulated via exploration of fully dilutable pre-concentrate GO system which could be a possible carrier to enhance oral bioavailability of GO.


Keywords


Ginger oleoresin, Dilutable SMEDDS, Mixed surfactant, Ex vivo permeation, Bioavailability, Solubilization

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References


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