Influence of the Preparation Method on the Physicochemical Properties of Tolbutamide/Cyclodextrin Binary Systems

Abstract

Tolbutamide (TBM) was found to form an inclusion complex with β-cyclodextrin (β-CD) in solution and in solid state. Inclusion complex formation between tolbutamide and β-cyclodextrin in aqueous solution was studied by phase solubility and spectral shift methods. The apparent stability constant K_s calculated by these techniques, in water, were estimated as 195.7 and 236.5 M⁻¹, respectively. The phase solubility studies revealed a B_S-type diagram with an inclusion complex of 1:2 molar ratio. The solid inclusion complexes of TBM and β-CD were prepared at a molar ratio of 1:2 by kneading, coprecipitation, freeze-drying, and spray-drying methods. In addition, the physical mixture was prepared. Characterization of TBM:β-CD inclusion was performed using differential scanning calorimetry (DSC), Raman spectroscopy, and X-ray diffractometry and by application of a so-called ether wash method. All the inclusion systems investigated led to a significant improvement in the dissolution over free TBM, and the dissolution rate of the active material was observed to be independent of the preparation method.

Key Words:

• Coprecipitation
• β-Cyclodextrin
• Freeze-drying
• Kneading
• Spray-drying
• Tolbutamide