Banca de DEFESA: POLYANNE NUNES DE MELO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : POLYANNE NUNES DE MELO
DATA : 15/02/2017
HORA: 09:00
LOCAL: Sala de Aulas do PPgDITM
TÍTULO:

.

PALAVRAS-CHAVES:

benznidazole; cyclodextrin; multicomponent complex; triethanolamine; 1-methyl-2-pyrrolidone; freeze-drying; cell viability

PÁGINAS: 164
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

The benznidazole (BNZ) has low aqueous solubility, which limits its bioavailability
and the development of pharmaceutical forms that allow a greater patients
compliance to the Chagas disease treatment. The purpose of the study was access
the interaction mechanism of this drug with beta-cyclodextrin (βCD), hydroxypropyl
beta-cyclodextrin (HPβCD) and randomly-methylated-beta-cyclodextrin (RMβCD), in
the presence and absence of the cosolvents triethanolamine (TEA) and methyl-1-
pyrrolidone-2 (NMP), aiming to obtain a pharmaceutical ingredient of greater
aqueous solubility or dissolution rate. The interactions between constituents in liquid
phase were acessed using the phase solubility diagrams, the Job's Plot method,
molecular modeling and 1H NMR spectroscopy. The solid phase complexes, obtained
by freeze-drying and physical mixing, were submitted to the dissolution test, and the
interactions between the constituents were access through FTIR, XRD, MEV, AFM,
BET, DSC and TG analysis. The cytotoxicity of the different complexes was analyzed
in Vero E6 cells and erythrocytes. The RMβCD was the most effective in increasing
the BNZ aqueous solubility, in the absence of TEA and NMP (13.8 times higher). The
BNZ is inserted preferably in the CDs cavity through its aromatic moiety. The TEA
and NMP changed the complexes structure and the complexation spontaneity.
Among the solid phase samples, the higher dissolution efficiency was achieved for
freeze-drying complexes, mainly for the BNZ:HPβCD:TEA. The FTIR, DSC and TG
analyzes confirmed the inclusion complexes formation by freeze-drying and showed
different interactions between the compounds when the cosolvents are present. The
TEA and NMP were able to change the appearance, roughness, porosity and surface
area of the particles. The cell viability and hemolysis studies revealed higher
cytotoxicity for the BNZ:RMβCD L, BNZ:RMβCD:TEA L, and BNZ:HPβCD:TEA L
complexes, but all complexes were safe for in vivo studies. The experimental results
showed the cosolvents contribution in BNZ dissolution, and demonstrated the TEA
and NMP action, in CDs presence, to obtain a new and promising excipient.

MEMBROS DA BANCA:
Interno - 434.316.903-00 - ALICE MARIA COSTA MARTINS - UFC
Presidente - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Externo à Instituição - MARCELA LONGHI - UNC/AR
Interno - 2203888 - MARCIA RODRIGUES PEREIRA
Externo à Instituição - THIAGO FRANCES GUIMARÃES - Fiocruz - RJ