Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) I: Use of Poloxamer 188 as Both Solidifying and Emulsifying Agent for Lipids

• Published in: Pharmaceutical research Vol. 29; no. 10; pp. 2817 - 2832
• Main Authors: Shah, Ankita V., Serajuddin, Abu T. M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2012; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Drug delivery systems; Drug Delivery Systems - methods; Emulsifying Agents - chemistry; Emulsions - chemistry; Fatty Acids - chemistry; Fenofibrate - chemistry; Glycerol - chemistry; Lipids; Medical Law; Particle Size; Pharmaceutical sciences; Pharmacology/Toxicology; Pharmacy; Poloxamer - chemistry; Polyethylene Glycols - chemistry; Probucol - chemistry; Research Paper; Solids; Solubility; Surfactants; Water - chemistry; self-emulsifying drug delivery systems; poloxamer 188; solid microemulsion preconcentrate; microemulsion; drug dispersion
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-012-0704-x

ABSTRACT Purpose To develop solid self-emulsifying drug delivery systems (SEDDS) for lipids using poloxamer 188 as both solidifying and emulsifying agents. Methods Mixtures of various lipids with poloxamer 188 and PEG 8000 were prepared at ~75°C. The molten mixtures, with and without dissolved drugs (fenofibrate and probucol), were then cooled to room temperature. When solids formed, they were characterized by powder XRD, DSC, microscopy using cross-polarization and confocal fluorescence techniques, dispersion test in water and particle size analysis of dispersions. Results When mixed with poloxamer 188 or PEG 8000, lipids consisting of monoesters of fatty acids with glycerol or propylene glycol formed solid systems, but not di- and tri-esters, which showed phase separation. Added to water, the solid systems containing poloxamer 188 started to disperse in water forming oil globules of 200–600 nm. No emulsification of lipids was observed from solids containing PEG 8000, indicating that the surfactant property of poloxamer 188 was responsible for emulsification. Powder XRD, DSC and microscopic examination revealed that poloxamer 188 and PEG 8000 maintained their crystallinity in solid systems, while the lipids were interspersed in between crystalline regions. The drug remained solubilized in the lipid phase. Conclusions A novel solid SEDDS is developed where the drug can be solubilized in liquid lipids and then the lipidic solution can be converted to solid mass by dispersing into the microstructure of poloxamer 188.