PEG and lipids in solid dispersions and liquid crystals - structure and phase behaviour
Doctoral thesis, 2008
In this thesis, two different kinds of nano-structured systems have been studied; solid dispersion systems of polyethylene glycol (PEG) and liquid crystalline systems containing the polar lipids monoolein (MO) and phytantriol (PT).
Solid dispersions of PEG were studied with addition of different substances, lipids or parabens. The dispersions have been examined in the solid state, using differential scanning calorimetry and X-ray methods with the focus of the behaviour of the PEG carrier material. It was found that incorporation of MO increased with decreasing PEG molecular weight and that MO addition also affected the lamellae thickness of PEG. Different lipids affected the structure of PEG differently. To find which properties of the lipid that governed the behaviour of the solid dispersions twelve different lipids in PEG 4000 were examined. All lipids increased the fraction of the PEG that was in its folded conformation where small and hydrophilic lipids increased the folding the most. The unfolding of the folded form to unfolded was slower with lipids present in the PEG. Large and hydrophobic lipids like triolein and tristearin stabilized the folded form most effectively.
The relation between solubility in a liquid PEG (PEG 400) and the structure of PEG 4000 solid dispersions was examined using a homologous series of parabens (methyl- to butyl- paraben). A high solubility in liquid PEG correlated to a high solubility in the solid dispersions and a larger increase of the lamellae thickness. The thickening of the lamellae was shown to be due to a swelling of the amorphous domains of the structure.
The studies of the liquid crystalline phases of MO and PT revealed large similarities. The two-component lipid-water systems are almost identical with the difference that the PT phases swell much less. In three component solvent-lipid-water systems (solvents: propylene glycol (PG), polyethylene glycol 400 (PEG 400) and 2-methyl-2,4-pentanediol (MPD)) the same differences could be seen between PT and MO where PT phases swelled less than MO. One other major difference was the formation of L3 phase. With MO L3 phase was found in all three solvent systems whereas it with PT was only found in the system with MPD, the most hydrophobic solvent. The differences between the PT and MO systems were explained by the fact that PT is more hydrophobic and forms less flexible bilayers.
bicontinuous sponge phase
bicontinuous cubic phase
differential scanning calorimetry
small angle X-ray diffraction