Physicochemical characterization and molecular modeling study of host–guest systems of aripiprazole and functionalized cyclodextrins

Abstract

Aripiprazole (ARP), an innovative atypical antipsychotic drug, exhibits very low aqueous solubility, affecting its dissolution and absorption and high lipophilicity. Its complexation with cyclodextrins (CDs) was designed to improve drug solubility and consequently its bioavailability. The inclusion complexes of aripiprazole with two β-cyclodextrin derivative, namely random methyl-β-cyclodextrin (RAMEB) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, were obtained and investigated both in solution and in solid state. The kneading method was used to prepare the inclusion complexes, and they were characterized with different analytical techniques, including thermal analysis, powder X-ray diffractometry, universal attenuated total reflectance Fourier-transform IR spectroscopy and UV spectroscopy. The stoichiometry of both APR/CDs inclusion complexes was found as 1:2 by employing continuous variation method. Benesi–Hildebrand equation was used for the apparent constant stability determination. Structural studies of the inclusion complexes were carried out using molecular modeling techniques in order to explain the complexation mechanism. The results of the studies demonstrate that the physicochemical properties of the kneaded products are different from ARP, testifying the inclusion complexes formation between aripiprazole and CDs when the kneading method is used. The solubility of the drug substance was improved upon complexation with CDs; higher increase in ARP solubility was noticed in the presence of RAMEB.