Direct Compression Tablets Containing a Series of Four β-Cyclodextrin Complexes Formed by Neutralizing an Acidic Drug

Abstract

A series of four β-cyclodextrin complexes (called products) was formed by neutralizing an acidic drug to study the effect of drug solubility on complex formation and the dissolution performance from direct compression tablets. Four solid products were prepared by neutralizing the drug in 0.05, 0.10, 0.20, and 0.30 M tromethamine solutions with a constant 0.09 M β-cyclodextrin concentration, filtering the solutions, and removing the water through evaporation with heat and vacuum. The four products contained drug and water in a distinct relationship, thus suggesting a complex formation that was dependent on the tromethamine concentration. Infrared, powder X-ray diffraction, differential scanning calorimetry (DSC), phase solubility, and scanning electron microscopy (SEM) techniques revealed distinct differences among the four products, suggesting three of the four products were complexes, and one product was either a weak complex or a physical mixture. Ultraviolet (UV) analysis showed no evidence of complex formation. Phase solubility results showed one product had a slight increase in drug solubility, and three products had no increase in drug solubility with increasing β-cyclodextrin concentration. The lack of a solubility increase suggests insoluble complex formation. Drug dissolution in water was improved significantly in all tablets containing either a product or a physical mixture when compared to the pure drug. The products prepared with the two highest concentrations of tromethamine showed a dissolution performance that was superior to all other formulations. Enthalpy measurements by DSC were a good indicator of dissolution performance for tablets containing the four products. Drug dissolution through salt formation in the absence of β-cyclodextrin showed the drug-salt dissolution varied from better to worse when compared to the dissolution profiles of the four products. The varying dissolution performance was attributed to the formation of distinct β-cyclodextrin complexes with varying solubilities.

Key Words:

• Complex formation
• β-Cyclodextrin
• Differential scanning calorimetry
• Direct compression tablets
• Dissolution
• Infrared
• Phase solubility
• Scanning electron microscopy
• Spectroscopy
• Thermogravimetric
• Tromethamine
• Ultraviolet
• X-ray diffraction