Poloxamer 188 (P188), which is a nonionic block linear copolymer with the poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) backbone, was selected as the solidifying cum emulsifying agent as it has structural similarities with solid PEGs that contain poly (ethylene oxide) backbone. P188 is composed of two hydrophilic side-chains attached to a hydrophobic center core and its average molecular weight of 8500 is comparable to that of PEG 8000 (mol wt08000), also, its hydrophilicity and HLB value (HLB029) are suitable to form oil-in-water emulsion.
Fig.1 Chemical structures of poloxamer 188. (Shah, 2012)
SEDDS was successfully prepared using P188 as a solidifying agent and thus the need for a liquid surfactant could be avoided or minimized and the lipid content could be increased. When the lipids composed of fatty acid monoester and glycerol or propylene glycol are mixed with P188 or PEG 8000, a solid system is formed without diester and triester, so it shows phase separation. After adding water, the solid system containing P188 began to disperse in water, forming oil beads of 200-600 nm. However, no emulsification of lipids was observed in the solid containing PEG8000, indicating that the surfactant property of P188 was the cause of emulsification. X-ray diffraction (XRD), differential scanning calorimetry (DSC), and microscopy showed that P188 and PEG8000 maintained crystallinity in the solid system, while lipids were dispersed between the crystalline regions. The drug is still dissolved in the lipid phase. Therefore, a new type of solid SEDDS was developed, in which the drug can be dissolved in liquid lipids, which are then converted to solid mass by the dispersion of the lipid solution into the microstructure of P188.
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