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
2003-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
