Direct compression tablets containing a series of four beta-cyclodextrin complexes formed by neutralizing an acidic drug

A series of four beta -cyclodextrin complexes (called products) was formed by neutralizing an acidic drug to study the effect of drug solubility on co mplex formation and the dissolution performance from direct compression tab lets. 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 beta -c yclodextrin 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 t hat was dependent on the tromethamine concentration. Infrared powder X-ray, diffraction, differential scanning calorimetry (DSC), phase solubility, an d scanning electron microscopy (SEM) techniques revealed distinct differenc es among the four products, suggesting three of the four products were comp lexes, and one product was either a weak complex or a physical mixture. Ult raviolet (UV) analysis showed no evidence of complex formation. Phase solub ility results showed one product had a slight increase in drug solubility, and three products had no increase in drug solubility with increasing beta -cyclodextrin concentration. The lack of a solubility increase suggests ins oluble complex formation. Drug dissolution in water was improved significan tly in all tablets containing either a product or a physical mixture when c ompared to the pure drug. The products prepared with the two highest concen trations of tromethamine showed a dissolution performance that was superior to all other formulations. Enthalpy measurements by DSC were a good indica tor of dissolution performance for tablets containing the four products. Dr ug dissolution through salt formation in the absence of beta -cyclodextrin showed the drug-salt dissolution varied from better to worse when compared to the dissolution profiles of the four products. The varying dissolution p erformance was attributed to the formation of distinct beta -cyclodextrin c omplexes with varying solubilities.