Goh, Soen Qeng
(2023)
Binary And Ternary Complexes Of Β-Cyclodextrin With Isoniazid And Ethambutol: Characterization And Molecular Modeling Studies.
Masters thesis, Universiti Sains Malaysia.
Abstract
Long term intake of antituberculosis drugs will lead to severe adverse reactions
that will ultimately deteriorate a patient’s health and well-being. Presently, it is known
that supramolecular macrocycles such as cyclodextrins (CDs) are useful to enhance
drug solubility and targeting mechanism while reducing drug dosage by providing
many therapeutic benefits. With that, the possibility of formation of drug-CDs ternary
inclusion complex was explored, whereby β-cyclodextrin (β-CD) was chosen as the
supramolecular host carrier to accommodate two kinds of first-line antituberculosis
guest drug molecules simultaneously, namely isoniazid (INH) and ethambutol (ETB).
The inclusion complex of β-CD/INH/ETB was prepared using solvent evaporation
method. Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic
resonance spectroscopy (1H-NMR), and 2-dimensional nuclear Overhauser effect
spectroscopy (2D-NOESY) NMR were used to investigate the functional groups and
structure of the complex. Scanning electron microscopy (SEM) and X-ray diffraction
(XRD) were employed to study the surface morphology and crystallinity changes
during complex formation. Thermogravimetric analysis (TGA) was performed to
investigate the thermal properties of the complex. FT-IR and both types of NMR
results had revealed the successful penetration of both the drug molecules into the β-
CD cavity. SEM images and XRD spectra had shown a drastic change in surface
structure and reduction in crystallinity during complex formation, which had indicated
successful formation of a new compound.
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