Formulation and physical characterization of water-in-oil microemulsions containing long- versus medium-chain glycerides

Stable self-emulsifying water-in-oil (w/o) microemulsions of extremely small particle size (5-30 nm) and consisting of an oil, a blend of a low and high HLB surfactants and an aqueous phase, have been developed using commercially available and pharmaceutically acceptable components. Their formation was monitored by the corresponding pseudo-ternary phase diagram. The oil phase contained long- or medium-chain triglycerides, and mono-/diglycerides or sorbitan esters (low HLB surfactants). Polysorbate 80 (Tween 80) was used as a high HLB surfactant. Microemulsions were readily prepared by admiring appropriate quantities of the various components with gentle hand-mixing or stirring to ensure thorough mixing. In the case of microemulsions incorporating long-chain glycerides and/or sorbitan esters, high temperature (40-60 degrees C) was used to reduce viscosity and solubilize all components during the formation of microemulsions. Limited levels of aqueous phase (<10%, w/w) can be solubilized within w/o microemulsions incorporating long-chain glycerides and/or sorbitan esters. Microemulsions containing medium-chain glycerides (mono-/di-/triglycerides) can be formulated at ambient temperature and can solubilize aqueous phase up to 40% (w/w). The conductance, viscosity, refractive index, density and mean particle diameter of a typical w/o microemulsion incorporating medium-chain glycerides (Captex 355/Capmul MCM/Tween 80/saline, 65/22/10/3, % w/w), were: 0.540 mu mhos/cm, 56.7 cP, 1.449, 0.9677, and 15.2 +/- 4.1 nm (polydispersity of 0.153), respectively. The corresponding values of a w/o microemulsion incorporating long-chain triglycerides and monoglycerides (Soybean oil/Arlacel 186/Tween 80/saline, 65/22/10/3, % w/w) were: 0.177 mu mhos/cm, 125.1 cP, 1.471, 0.9010, and 10.3 +/- 2.5 nm (polydispersity of 0.114), respectively. Several water-soluble molecules/peptides of different molecular size and charge have been formulated in these w/o microemulsions at pharmacological relevant levels. These systems are discussed in terms of their drug delivery potential. (C) 1997 Elsevier Science B.V.