Phase Behavior of Non-Ionic Surfactant-Medium Chain Triglyceride-Water Microemulsion Systems

Microemulsion systems have garnered tremendous interest in the pharmaceutical sector for a variety of drug delivery applications. Non-ionic surfactants are often the preferred surfactant class given their uncharged nature, enhanced oral safety profile, and generally regarded as safe status as compared to other surfactant classes (Myers, Surfactant science and technology, 2005, p. 29), (Malmsten, Handbook of microemulsion science and technology, 1999, p. 755), (Grove & Mullertz, Chapter 5-liquid self-microemulsifying drug delivery systems, 2007), (Liu et al., Water-insoluble drug formulation, 2008), (Hauss, Advanced Drug Delivery Reviews, 2007, 59, pp. 667–676), (Balazs, Solubility, delivery and ADME problems of drugs and drug-candidates, 2011, p. 68). In this work, the phase behavior and microemulsion formation potential of four commonly used non-ionic surfactants, PEG-40 hydrogenated castor oil, Poloxamer 188, Polysorbate 80, and d -α-tocopherol polyethylene glycol succinate were studied via ternary phase diagram (TPD) mapping using a medium chain triglyceride, Miglyol 812. Results indicated notable differences in phase behavior despite similarities in hydrophilic–lipophilic balance value (13–15). All surfactants produced Winsor Type I, oil-in-water microemulsions at water concentrations above 40% wt/wt. Winsor Type II water-in-oil microemulsions were difficult to obtain even at high oil concentrations of ≥70% wt/wt. Winsor III microemulsions, though rare, were generally obtained in the middle regions of the TPD between 10% and 30% wt/wt water while Winsor IV microemulsions dominated at high surfactant concentrations of ≥45% wt/wt. Opaque emulsion areas were particularly notable in wax state surfactants. Polysorbate 80 and PEG-40 hydrogenated castor oil demonstrated a high degree of synergism as well as the largest oil-in-water (o/w) and water-in-oil (w/o) microemulsion formation potential rendering them suitable for a number of enteral and parenteral applications.