Biphenylylacetic acid (BPAA) was linked to the free hydroxyl group of 2,6-di-O-methyl-β-Cyclodextrin (DM-β-CyD) through an ester linkage to obtain the site specific release of the drug to the colon. The conjugate at 1:1 mole ratio was separated from the reaction mixture by semipreparative reverse-phase HPLC and characterized by 1H-NMR, 13C-NMR, IR spectroscopy, mass spectrometry and elemental analysis. Chemico-physical characteristics, such as water solubility and dissolution rate, were evaluated comparatively to the BPAA-DM-β-CyD inclusion complex. Hydrolysis rates were investigated in media simulating gastro-intestinal fluids and at pH 7.4 in the presence of porcine liver esterase. A rapid release of the drug was observed at acid pH value. In all cases a first order kinetic was observed, characterized by t1/2 value of 1.19, 19 and 4 h for chemical hydrolysis at pH 1.1, at pH 7.4 and enzymatic hydrolysis, respectively. In vitro permeation studies through caco-2 cells confirmed the ability of DM-β-CyD to increase the absorption of included BPAA. A slow permeation was observed for the drug conjugate to DM-β-CyD due to the slow release of BPAA.

Synthesis, Characterization and In Vitro Evaluation of Dimethyl-β-cyclodextrin-4-biphenylylacetic Acid Conjugate

PISTARA', Venerando;PUGLISI, Giovanni
2003

Abstract

Biphenylylacetic acid (BPAA) was linked to the free hydroxyl group of 2,6-di-O-methyl-β-Cyclodextrin (DM-β-CyD) through an ester linkage to obtain the site specific release of the drug to the colon. The conjugate at 1:1 mole ratio was separated from the reaction mixture by semipreparative reverse-phase HPLC and characterized by 1H-NMR, 13C-NMR, IR spectroscopy, mass spectrometry and elemental analysis. Chemico-physical characteristics, such as water solubility and dissolution rate, were evaluated comparatively to the BPAA-DM-β-CyD inclusion complex. Hydrolysis rates were investigated in media simulating gastro-intestinal fluids and at pH 7.4 in the presence of porcine liver esterase. A rapid release of the drug was observed at acid pH value. In all cases a first order kinetic was observed, characterized by t1/2 value of 1.19, 19 and 4 h for chemical hydrolysis at pH 1.1, at pH 7.4 and enzymatic hydrolysis, respectively. In vitro permeation studies through caco-2 cells confirmed the ability of DM-β-CyD to increase the absorption of included BPAA. A slow permeation was observed for the drug conjugate to DM-β-CyD due to the slow release of BPAA.
4-biphenylylacetic acid; Chemical and enzymatic hydrolysis; Chemical conjugate; Dimethyl-β-cyclodextrins; Permeation through caco-2 cells
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/40113
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