Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.
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.
Dollo
Gilles
G
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
Le Corre
Pascal
P
Guérin
Alexis
A
Chevanne
François
F
Burgot
Jean Louis
JL
Leverge
Roger
R
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
D004655:Emulsions; D009821:Oils; D011134:Polysaccharides; D014867:Water; C008315:maltodextrin