Preparation and Characterization of the β-Cyclodextrin Inclusion Complex with Benzbromarone

• Published in: Journal of the Brazilian Chemical Society Vol. 31; no. 8; pp. 1585 - 1596
• Main Authors: Sousa, Iran, Porto, Caio, Bassani, Kátia, Martins, Milene, Pessine, Francisco, Morgon, Nelson
• Format: Journal Article
• Language: English
• Published: Sociedade Brasileira de Química 01-08-2020
• Subjects: CHEMISTRY, MULTIDISCIPLINARY; inclusion complex; ONIOM(CIS:PM6); benzbromarone; fluorescence; ONIOM(TD-DFT:PM6); β-cyclodextrin
• ISSN: 0103-5053; 1678-4790
• DOI: 10.21577/0103-5053.20200044

Benzbromarone (BZB) is a drug that has diuretic activity and is used in the gout treatment. Its therapeutic efficiency is decreased by its low water solubility (11.8 mg L-1) and highly hydrophobic aspect (logP 2.7), which are responsible for affecting its intestinal absorption and bioavailability. BZB inclusion complex (IC) aims at increasing the drug solubility in water and reduce adverse effects resulting in more efficient formulations. The coprecipitation encapsulating method was used to obtain the IC of BZB in β-cyclodextrin (β-CD) and the complex (BZB@β-CD) was characterized via physical-chemical analysis. A comparative study of time-dependent density functional theory (TD-DFT) and configuration interaction singles (CIS), along with “our own N-layered integrated molecular orbital and molecular mechanics” (ONIOM) method, has been carried out on the UV-Vis absorption of BZB and BZB@β-CD. The qualitative description of the simulated spectrum, given by ONIOM(CIS:PM6), is in accord with the formation of BZB@β-CD. It only became possible when phosphate buffer (pH 7.4) was used to prepare the solutions, since the complex formation did not occur in deionized water or buffered acid. Furthermore, by using the Job plot, the Scatchard method and fluorescence, it was possible to conclude that the complex molecular stoichiometry was 1:1 (1 BZB to 1 β-CD).