Development of Solid SEDDS, II: application of Acconon® C-44 and Gelucire® 44/14 as solidifying agents for self-emulsifying drug delivery systems of medium chain triglyceride.

Self-emulsifying drug delivery systems (SEDDS) are usually isotropic liquids consisting of drugs, lipids, surfactants and/or co-surfactants that spontaneously form fine oil-in-water emulsions in contact with water. Since a solid dosage form has better patient acceptance than a liquid, it was investigated whether liquid SEDDS containing medium-chain lipids (mono- or tri-glycerides) may be converted to solids or semisolids using lauroyl polyoxyl glycerides (Acconon® C-44, ABITEC, and Gelucire® 44/14, Gattefosse) as solidifying agents. Acconon® C-44 and Gelucire® 44/14 were melted at 65EC. The liquid lipids or the liquid lipidsurfactant mixtures, with and without dissolved drug (probucol), were mixed with the melts, and the hot liquid solutions were filled into hard gelatin capsules. The solutions solidified inside the capsules when cooled to room temperature. Acconon® C-44 and Gelucire® 44/14 had a greater propensity for solidifying the triglyceride of medium chain fatty acids (Captex® 355, ABITEC) rather than the monoglyceride. Powder XRD, DSC and microscopic analyses indicated that the lauroyl polyoxyl glycerides crystallized at room temperature, while the lipid or the lipid-surfactant mixtures present in the formulations remained interspersed in between solids as a separate liquid phase. The drug remained dissolved in the liquid phase and there was no crystallization of the drug. Although Acconon® C-44 and Gelucire® 44/14 are themselves surface active, the dispersion testing using the USP apparatus II at 50 rpm and 37EC using 250 ml of 0.01N HCl as the dispersion medium showed that a second surfactant (Cremophor® EL®, BASF) was required in the solid formulation to maximize drug release and dispersion. Formulations containing 1:1 and 3:1 w/w ratios of Captex® 355 and Cremophor® EL produced lipid particles in the range of 200 to 450 nm. Thus, a novel approach of preparing solid SEDDS resulting in submicron emulsions with particle size <500nm is presented.