The influence of cosurfactants and oils on the formation of pharmaceutical microemulsions based on PEG-8 caprylic/capric glycerides.
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) to solubilize both oil and water phases was evaluated. Seven different cosurfactants (polyglyceryl-6 dioleate (Plurol Oleique) (PO), polyglyceryl-6 isostearate (Plurol Isostearique (PI), polyglyceryl-4 isostearate (Isolan GI 34) (IGI34), octoxynol-12 (and) polysorbate 20 (Solubilisant gamma) 2421) (SG2421), octoxynol-12 (and) polysorbate 20 (and) PEG-40 hydrogenated castor oil (Solubilisant gamma 2429) (SG2429), PEG-40 hydrogenated castor oil (Cremophor) RH 40) (CRH40) and diethyleneglycol monoethyl ether (Transcutol) 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/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) (S min, %w/w), the minimal concentration of the surfactant/cosurfactant blend required to produce a balanced microemulsion (SCoS min, %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 showed a good efficiency in the presence of lower molecular volume fatty acid esters with a preferred chemical structure such as isopropyl myristate (S min 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 decreased the capacity of Labrasol for solubilization of oil and water phases. The tendency of Labrasol 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 in the formation of microemulsions using isopropyl myristate as oil phase. Optimized microemulsion systems were stabilized with Labrasol/polyglyceryl-6 esters blend at K(m) 5:5 (SCoS min, 27.5% (w/w) and W(max), 71.43% (w/w) for PI; SCoS min, 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.
Djekic
Ljiljana
L
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia. ljiki@pharmacy.bg.ac.yu
Primorac
Marija
M
D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D005989:Glycerides; D005990:Glycerol / Q000737:chemistry*; D009821:Oils / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry*
D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D009821:Oils; D009930:Organic Chemicals; D011108:Polymers; D013501:Surface-Active Agents; C440220:Labrasol; D014867:Water; C043941:polyglycerol; D011092:Polyethylene Glycols; D005990:Glycerol