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

Abstract

A self-emulsifying drug delivery system (SEDDS) is usually an isotropic liquid consisting of drug, lipid, surfactant and/or co surfactant that spontaneously form fine oil-in-water emulsion in contact with water. Since a solid dosage form is more preferable than a liquid, the present investigation was undertaken to determine whether liquid SEDDS containing medium-chain lipids (mono- or tri-glycerides) may be converted to solids by using lauroyl polyoxyl glycerides (Acconon C-44; ABITEC and Gelucire 44/14; Gattefosse) as solidifying agents such that the formulations may be filled into hard gelatin capsules. For the preparation of solid formulations, Acconon C-44 and Gelucire 44/14 were melted at 65?C, a liquid lipid or a liquid lipid-surfactant mixture with and without dissolved drug (Probucol) were added to them, and the hot liquid were filled into hard gelatin capsules. The melts were then allowed to solidify inside capsules. The results showed that a triglyceride of medium chain fatty acids (Captex 355; ABITEC), and not monoglycerides, could be solidified by this method. The powder X-ray diffraction, differential scanning calorimetric and microscopic analysis 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 drug. Dispersion testing of the solid systems using 250 mL 0.01N HCl as dispersion medium and the USP dissolution apparatus II at 50 rpm and 37 ?C showed that, although Acconon C-44 and Gelucire 44/14 are themselves surface active in nature, a second surfactant (Cremophor EL; BASF) was needed as the co-surfactant to maximize drug release and dispersion from the system. Formulations containing 1:1 and 3:1 ratios of Captex 355 and Cremophor EL produced lipid particles in the range of 200 to 450 nm. Thus, the report presents a novel approach of preparing SEDDS that results into very fine emulsion with particle size ranging in <500nm.