title: Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.
abstract: A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug. 5-PDTT release from the solid state emulsion was studied using an in vitro two-phase stirred model and the relative bioavailability of 5-PDTT in the dry emulsion was obtained in the rabbit after oral administration of the reconstituted emulsion, compared to a 5-PDTT-sulfobutyl ether 7 beta-cyclodextrin complex in solution. Incorporation of 5-PDTT in the oil phase neither affects the surface morphology of the powder nor the reconstitution, the droplet size or the drug releasing properties and, furthermore, allows a 3-fold improvement of 5-PDTT relative bioavailability in rabbit after oral administration. These results indicate that dry emulsions may be considered as relevant dosage forms to improve bioavailability of poorly absorbable lipophilic drugs.
authors.affiliation: Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes, Cedex, France. gilles.dollo@univ-rennes1.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Dollo
authors.forename: Pascal
authors.initials: P
authors.lastname: Le Corre
authors.forename: Alexis
authors.initials: A
authors.lastname: Guérin
authors.forename: François
authors.initials: F
authors.lastname: Chevanne
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Burgot
authors.forename: Roger
authors.initials: R
authors.lastname: Leverge
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D004655:Emulsions / Q000737:chemistry* / Q000493:pharmacokinetics*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D009821:Oils; D011134:Polysaccharides / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013997:Time Factors; D014867:Water
chemical_list: D004655:Emulsions; D009821:Oils; D011134:Polysaccharides; D014867:Water; C008315:maltodextrin