BIOAVAILABILITY STUDY OF TOLBUTAMIDE BETA-CYCLODEXTRIN INCLUSION-COMPOUNDS, SOLID DISPERSIONS AND BULK POWDER

Tolbutamide PEG 6000 solid dispersions as well as tolbutamide beta-cyc lodextrin complexes were prepared with a view to increasing the bioava ilability of this poorly soluble drug. Absolute and relative bioavaila bilities were determined by comparison with the administration of a co mmercial solution of the drug. The study was carried out in rabbits (n = 5 per dosage form). The aqueous solution of tolbutamide (Dolipol(R) ) 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 co ncentrations were measured by an HPLC method. Our results indicate tha t the absorption of tolbutamide is not increased in comparison with ei ther bulk powder or a solution of the drug. However, there are obvious differences in the kinetics of absorption: indeed, tolbutamide is abs orbed rapidly from the complex and the bulk powder. The process of abs orption is much slower for the other dosage forms. Finally, even if th e quantitative part of bioavailability is not modified, complexation w ith cyclodextrins could be interesting in order to increase the kineti c process of absorption of poorly soluble drugs.