IMPROVEMENT OF SOME PHARMACEUTICAL PROPERTIES OF DRUGS BY CYCLODEXTRIN COMPLEXATION .4. CHLORPROMAZINE HYDROCHLORIDE

The potentiality of interaction of chlorpromazine hydrochloride (CPZ) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometry , vapour pressure osmometry and DSC thermograms. The results revealed a very strong evidence for molecular interaction between CPZ and beta- CD. The continuous variation method was used to elucidate the stoichio metry of such interaction by spectrophotometric as well as vapour pres sure measurements. Both types of data revealed the formation of a 1:1 complex. The stability constant of the complex was determined at diffe rent temperatures by the vapour pressure osmometric method. The enthal py and entropy of interaction were evaluated and the results indicate that the interaction is exothermic. The CPZ/beta-CD complex was prepar ed, lyophilized and photochemical stability of the drug, its physical mixture with beta-CD as well as the prepared complex was investigated at different pH-values in presence of different buffer systems. The re sults revealed that the stability of the drug is greatly improved in p resence of beta-CD and the great dependency of stability on the pH of the solution is decreased in presence of beta-CD. The partition coeffi cient of CPZ and its complex with beta-CD was determined. The data rev eal a higher p.c. of the complex compared to the parent drug. The effe ct of beta-CD on the bioavailability of CPZ was investigated by measur ing the miotic response intensity in volunteers receiving a single ora l dose of the drug, drug/beta-CD physical mixture or complex, The resu lts revealed a distinct improvement of the biological performance of C PZ by beta-CD as evidenced by an increased intensity of drug action an d its duration as well as augmenting its bioavailability without affec ting the time for maximum effect.