The influence of cosurfactants and oils on the formation of pharmaceutical microemulsions based on PEG-8 caprylic/capric glycerides

Abstract

In the present study the effect of type and concentration of a cosurfactant and oil on the ability of nonionic surfactant PEG-8 caprylic/capric glycerides (Labrasol (R)) to solubilize both oil and water phases was evaluated. Seven different cosurfactants (polyglyceryl-6 dioleate (Plurol Oleique (R)) (PO), polyglyceryl-6 isostearate (Plurol Isostearique (R)) (PI), polyglyceryl-4 isostearate (Isolan (R) GI 34) (IGI34), octoxynol-12 (and) polysorbate 20 (Solubilisant gamma (R) 2421) (SG2421), octoxynol-12 (and) polysorbate 20 (and) PEG-40 hydrogenated castor oil (Solubilisant gamma (R) 2429) (SG2429), PEG-40 hydrogenated castor oil (Cremophor (R) RH 40) (CRH40) and diethyleneglycol monoethyl ether (Transcutol (R))) and six oils (isopropyl myristate, ethyl oleate, decyl oleate, medium chain triglycerides, mineral oil and olive oil) were used in phase behaviour studies of a quaternary system Labrasol (R)/cosurfactant/oil/water. The amount of surfactant required to completely homogenize equal masses of oil and water to form a single phase microemulsion (termed as balanced microemulsion) (Smin, %w/w), the minimal concentration of the surfactant/cosurfactant blend required to produce a balanced microemulsion (SCoSmin, %w/w) as well as the maximum concentration of water solubilized in investigated surfactant/oil and surfactant/cosurfactant/oil mixtures (W-max, %w/w) were determined. The obtained results indicated that Labrasol (R) showed a good efficiency in the presence of lower molecular volume fatty acid esters with a preferred chemical structure such as isopropyl myristate (Smin 56.14% (w/w); W-max 12.28% (w/w)). Oils with high molecular volume (olive oil and mineral oil) do not result in microemulsion formation. Transcutol (R) decreased the capacity of Labrasol (R) for solubilization of oil and water phases. The tendency of Labrasol (R) to solubilize both, water and oil phases, was favoured by polyglycerol-6 ester type of cosurfactants (PO and PI) while the influence of the polyglycerol-4 ester (IGI34) as well as of polyoxyethylene type of cosurfactants (CRH40, SG2421 and SG2429) on the surfactant efficiency, was not significant. Furthermore, the results revealed the significant influence of the surfactant/cosurfactant mass ratio (K-m) on synergistic effect between polyglyceryl-6 esters and Labrasol (R) in the formation of microemulsions using isopropyl myristate as oil phase. Optimized microemulsion systems were stabilized with Labrasol (R)/polyglyceryl-6 esters blend at K-m 5:5 (SCoSmin, 27.5% (w/w) and W-max, 71.43% (w/w) for PI; SCoSmin, 29.18% (w/w) and W-max, 65.00% (w/w) for PO) and the electrical conductivity measurement results for optimized balanced microemulsions showed that their structures were highly conductive indicating a bicontinuous microstructure.