title: Monoacyl phosphatidylcholine inhibits the formation of lipid multilamellar structures during in vitro lipolysis of self-emulsifying drug delivery systems.
abstract: The colloidal structures formed during lipolysis of self-emulsifying drug delivery systems (SEDDS) might affect the solubilisation and possibly the absorption of drugs. The aim of the current study is to elucidate the structures formed during the in vitro lipolysis of four SEDDS containing medium-chain glycerides and caprylocaproyl polyoxyl-8 glycerides (Labrasol), with or without monoacyl phosphatidylcholine (MAPC). In situ synchrotron small-angle X-ray scattering (SAXS) was combined with ex situ cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) to elucidate the generated structures. The SAXS scattering curves obtained during the lipolysis of MAPC-free SEDDS containing 43-60% w/w Labrasol displayed a lamellar phase peak at q=2.13nm-1that increased with Labrasol concentration, suggesting the presence of multilamellar structures (MLS) with a d-spacing of 2.95nm. However, SEDDS containing 20-30% w/w MAPC did not form MLS during the lipolysis. The cryo-TEM and DLS studies showed that MAPC-free SEDDS formed coarse emulsions while MAPC-containing SEDDS formed nanoemulsions during the dispersion in digestion medium. From the first minute and during the entire lipolysis process, SEDDS both with and without MAPC generated uni-, bi-, and oligo-lamellar vesicles. The lipolysis kinetics in the first minutes of the four SEDDS correlated with an increased intensity of the SAXS curves and the rapid transformation from lipid droplets to vesicles observed by cryo-TEM. In conclusion, the study elucidates the structures formed during in vitro lipolysis of SEDDS and the inhibitory effect of MAPC on the formation of MLS.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Thuy
authors.initials: T
authors.lastname: Tran
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Scheyla D V S
authors.initials: SDVS
authors.lastname: Siqueira
authors.affiliation: Institute for Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9/V, A-8010 Graz, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Amenitsch
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Bioneer: FARMA, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: anette.mullertz@sund.ku.dk.
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
mesh_terms: D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D007700:Kinetics; D008066:Lipolysis; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D012995:Solubility
chemical_list: D004655:Emulsions; D005079:Excipients; D005989:Glycerides; D010713:Phosphatidylcholines; C440220:Labrasol
keywords: Colloidal structures; Cryogenic transmission electron microscopy; In vitro lipolysis; Monoacyl phosphatidylcholine; Self-emulsifying drug delivery systems; Small-angle X-ray scattering