Bioavailability study of tolbutamide β-cyclodextrin inclusion compounds, solid dispersions and bulk powder

Tolbutamide PEG 6000 solid dispersions as well as tolbutamide β-cyclodextrin complexes were prepared with a view to increasing the bioavailability of this poorly soluble drug. Absolute and relative bioavailabilities were determined by comparison with the administration of a commercial solution of the drug. The study was carried out in rabbits (n = 5 per dosage form). The aqueous solution of tolbutamide (Dolipol®) was administered either intravenously (10 mg/kg) or orally (20 mg/kg). Bulk powder, comelt, coprecipitate and solid complex of tolbutamide were administered orally at a dose of 20 mg/kg. Plasma tolbutamide concentrations were measured by an HPLC method. Our results indicate that the absorption of tolbutamide is not increased in comparison with either bulk powder or a solution of the drug. However, there are obvious differences in the kinetics of absorption: indeed, tolbutamide is absorbed rapidly from the complex and the bulk powder. The process of absorption is much slower for the other dosage forms. Finally, even if the quantitative part of bioavailability is not modified, complexation with cyclodextrins could be interesting in order to increase the kinetic process of absorption of poorly soluble drugs.