Enhanced Solubility of Albendazole in Cyclodextrin Inclusion Complex: A Molecular Modeling Approach and Physicochemical Evaluation.

Autor:	de Melo CG; Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil., da Costa LAG; Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil., Rabello MM; Central de Análise de Fármacos Medicamentos e Alimentos, Universidade Federal do Vale do São Francisco, Petrolina/PE, Brazil., de Albuquerque Wanderley Sales V; Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil., Ferreira AS; Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil., da Silva PCD; Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil., Nishimura RHV; Central de Análise de Fármacos Medicamentos e Alimentos, Universidade Federal do Vale do São Francisco, Petrolina/PE, Brazil., da Silva RMF; Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil., de Araújo Rolim L; Central de Análise de Fármacos Medicamentos e Alimentos, Universidade Federal do Vale do São Francisco, Petrolina/PE, Brazil., Neto PJR; Laboratório de Tecnologia dos Medicamentos, Universidade Federal de Pernambuco, Recife/PE, Brazil.
Jazyk:	angličtina
Zdroj:	Current drug delivery [Curr Drug Deliv] 2022; Vol. 19 (1), pp. 86-92.
DOI:	10.2174/1567201818666210614104234
Abstrakt:	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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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