Methotrexate transport from the internal phase of multiple w/o/w emulsions

Release rates of Methotrexate (MTX) encapsulated in the internal phase of w/o/w emulsions stabilized by the interfacial interaction between albumin and sorbitan mono-oleate(Tween 80) were measured as functions of two formulation variables--the oil phase and the secondary emulsifier composition. The release rate was significantly affected by the nature of the oil phase and decreased in the order isopropyl myristate greater than octadecane greater than hexadecane greater than dodecane greater than octane, which was a reflection of the increasing internal droplet size of the emulsions. The release rate data conform with first order kinetics. Comparison of the effective permeability coefficients calculated from the experimental apparent first-order rate constants, with the effective permeability coefficient of water in planar oil layers, containing non-ionic surfactants, determined by a microgravimetric method supported the hypothesis of diffusion of MTX in water loaded inverse micelles. Surfactants with high HLB values, used as the secondary hydrophilic emulsifier increased the release rates, primarily by increasing the rate of diffusion of MTX through the non-aqueous liquid membrane.