Preparação e caracterização de complexo de inclusão de 2-hidroxipropil-β-ciclodextrina contendo 6CN10

Abstract

The 6CN10 is a 2-amino-thiophene derivative obtained from 2-amino-4,5,6,7tetrahydro-4H-benzo[b]thiophene-3-carbonitrile

obtained through the reaction of Gewald, followed by condensation with 4-nitrobenzaldehyde. This drug showed good antifungal activity in in vitro tests, especially against Cryptococcus sp. and can be considered as a promising molecule for the development of a new antifungal drug. However, the therapeutic potential of 6CN10 is limited by its low water solubility. The formation of inclusion complexes between drugs poorly soluble in aqueous media and cyclodextrin has been one of the most used techniques to improve the solubility profile of drugs with low solubility in water. The present work aimed at obtaining inclusion complexes between 6CN10 and 2-hydroxypropyl-β-cyclodextrin and the characterization of this system. The inclusion complex of 2-hydroxypropyl-βcyclodextrin

(HP-β-CD) and 6CN10 was prepared using the technique of lyophilization and characterized using the phase-solubility diagram, thermal analysis, FT-IR and Raman spectroscopy, X-ray diffraction and scanning electron microscopy. The phase solubility studies revealed a curve-type AL, suggesting the formation of inclusion complexes with 1:1 stoichiometry with a constant of stability of 96M . The water solubility of 6CN10 (2.4µg/mL) increased more than 29 times in the presence of 0.36M of HP-β-CD. Thermogravimetric analysis showed that the thermal stability of 6CN10 in the inclusion complex was improved due to additional interactions between the host and guest molecule. The reduction in the intensity and position of peaks in the spectra of FT-IR and Raman and the change in the crystallinity pattern of the complex 6CN10:HP-β-CD together with the observation of a product with features of a new amorphous single phase by scanning electron microscopy confirmed the formation of the inclusion complex.