Formulations based on alpha cyclodextrin and soybean oil: an approach to modulate the oral release of lipophilic drugs.
The purpose of this work was to investigate the potential of α-cyclodextrin combined to soybean oil-based formulations to modulate the release of a model drug, indomethacin. Dry emulsion, naked and coated beads were prepared from the same initial formulation using the same manufacturing process. Dry emulsion was selected to accelerate drug release while beads coated with α-cyclodextrin were designed to sustain it. Indomethacin-loaded systems were prepared, characterised and evaluated in vitro. Pharmacokinetic studies were performed in fasted and fed rats. The presence of the α-cyclodextrin coat was confirmed by confocal microscopy, and an increase of the mass and diameter of the beads. The layer of α-cyclodextrin improved their resistance in simulated gastro-intestinal fluids. In vitro, the dissolution of indomethacin was slower with coated beads than with emulsion and naked beads. Lipid-based formulations showed an increase of relative bioavailability of IND versus Indocid®. Whatever the formulation, greater and faster release of indomethacin was noticed in sodium taurocholate-rich medium and in fed rats. Compared to naked beads, an increased Cp(max) with a shorter T(max) was observed with the emulsion while T(max) and MRT were increased and Cp(max) reduced with the coated beads. Interestingly, formulations based on alpha cyclodextrin and soybean oil can modify the release of a lipophilic drug depending on the system formed.
CNRS UMR 8612, Physico-chimie-Pharmacotechnie, Biopharmacie, IFR 141, Faculté de Pharmacie, Univ Paris-Sud, 5 Rue Jean-Baptiste Clement, Châtenay-Malabry 92296, France.
M C
MC
Hamoudi
F
F
Bourasset
V
V
Domergue-Dupont
C
C
Gueutin
V
V
Nicolas
E
E
Fattal
A
A
Bochot
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004655:Emulsions; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D047391:alpha-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D004337:Drug Carriers; D004655:Emulsions; D047391:alpha-Cyclodextrins; D013024:Soybean Oil; D007213:Indomethacin; C032613:alpha-cyclodextrin