Title:Enhanced Solubility of Albendazole in Cyclodextrin Inclusion Complex: A
Molecular Modeling Approach and Physicochemical Evaluation
Volume: 19
Issue: 1
Author(s): Camila Gomes de Melo*, Lucas Amadeu Gonzaga da Costa, Marcelo Montenegro Rabello, Victor de Albuquerque Wanderley Sales, Aline Silva Ferreira, Paulo César Dantas da Silva, Rodolfo Hideki Vicente Nishimura, Rosali Maria Ferreira da Silva, Larissa de Araújo Rolim and Pedro José Rolim Neto
Affiliation:
- Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil
Keywords:
Cyclodextrin, in silico studies, kneading, immediate release, Albendazole, inclusion complex.
Abstract:
Background: Albendazole (ABZ) is the drug of choice for the treatment of a variety of
human and veterinary parasites. However, it has low aqueous solubility and low bioavailability. Cyclodextrins
(CD) are pharmaceutical excipients with the ability to modulate the solubilization property
of hydrophobic molecules.
Objective: The aim of the study was to analyze through in vitro and in silico studies (Autodock Vina
software and CycloMolder platform) the formation of inclusion complexes between ABZ, β-cyclodextrin
(β-CD) and its derivatives Methyl-β-cyclodextrin (M-β-CD) and Hydroxypropyl-β-cyclodextrin
(HP-β-CD).
Methods: The most stable inclusion complexes were produced by the kneading method and characterized
by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC),
X-Ray Diffraction (XRD), determination of the ABZ content and in vitro dissolution profile.
Results: Molecular modeling revealed that inclusion complexes between HP-β-CD:ABZ (in the
proportion 1:1 and 2:1) presented the lowest formation energy and the highest number of intermolecular
interactions, showing that the use of more cyclodextrins does not generate gains in the
stability of the complex. On the characterization tests, the complexes experimentally obtained by
the kneading method demonstrated highly suggestive parameters, including ABZ in HP-β-CD in
both molar proportions, suppression of bands in the infrared spectrum, displacement of the drug's
melting temperature in DSC, crystallinity halos instead of the characteristic peaks of ABZ crystals
in the XRD and a release of more than 80% of ABZ in less than 5 minutes, dissolution efficiency
of up to 92%.
Conclusion: In silico studies provided a rational selection of the appropriate complexes of cyclodextrin,
enabling the elaboration of more targeted complexes, decreasing time and costs for elaboration
of new formulations, thereby increasing the oral biodisponibility of ABZ.
