Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 1. Allopurinol

The potentiality of molecular interaction of allopurinol (1) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometric methods. Differential UV spectrophotometry revealed an increase in the optical density of 1 in presence of beta-CD. Application of the continuous variation method to spectrophotometric measurements was attempted and revealed the formation of an 1:1 complex between 1 and beta-CD. The apparent solubility of the drug in presence of beta-CD was investigated at different temperatures. The solubility-potentiating effect increases with increasing beta-CD concentration at 25-45 degrees C. On the other hand, the solubility of 1 decreases in presence of beta-CD at 60 degrees C. The amount of drug solubilized in the form of the complex was determined at different temperatures and the results revealed that the solubilizing effect of beta-CD is entirely due to complex-formation. The stability constant of the complex was determined at different temperatures. The enthalpy and entropy of interaction were also computed from the values of the stability constant of the complex at different temperatures. The large negative enthalpic value indicates a strong involvement of dipoles and van der Waals interaction during complexation. The dissolution profiles of the drug, physical mixture of the drug and beta-CD as well as the prepared complex show an enhancement of drug dissolution from the prepared complex or the physical mixture compared to the drug per se which reveals an improvement of the dissolution property of 1 by beta-CD complexation.