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• W4297524384 endingPage "2073" @default.
• W4297524384 startingPage "2073" @default.
• W4297524384 abstract "The poor aqueous solubility and/or permeability and thereby limited bioavailability largely restricts the pharmaco-therapeutic implications of potent anticancer drugs such as methotrexate (MTX). Furthermore, MTX’s inherently unstable nature makes it difficult to develop a viable oral formulation. In this study we developed the spray-dried amorphous inclusion complexes of MTX with native β-cyclodextrin (β-CD) and its derivatives, namely HP-β-CD, M-β-CD, and DM-β-CD to enhance the aqueous solubility, photostability, permeability, and oral bioavailability of MTX in rats. Our findings show that the 1:1 stoichiometry ratio of MTX and CDs improves the aqueous solubility, stability, and pharmacokinetic profiles of the drug, the better results being obtained particularly with DM-β-CD as a host, which has a higher complexation ability with the drug compared to other β-CDs. Specifically, the pharmacokinetic analysis demonstrated 2.20- and 3.29-fold increments in AUC and Cmax, respectively, in comparison to free MTX. Even though the absorptive permeability of MTX and MTX/DM-β-CD inclusion complexes was similar, the efflux of the absorbed MTX from ICs was significantly lower compared to the free MTX (4.6- vs. 8.0-fold). Furthermore, the physicochemical characterization employing SEM, DSC, and PXRD confirmed the transformation of crystalline MTX to its amorphous state. In solution, 1H NMR studies revealed that MTX embedded into the DM-β-CD cavity resulting in both H-3 and H-5 chemical shifts implied the presence of intermolecular interaction between the drug and CD moiety. It was, therefore, evident that an MTX IC could be a successful oral formulation technique, preventing MTX degradation and enhancing its pharmacologically relevant properties." @default.
• W4297524384 created "2022-09-29" @default.
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• W4297524384 date "2022-09-28" @default.
• W4297524384 modified "2023-10-18" @default.
• W4297524384 title "Alternative Methotrexate Oral Formulation: Enhanced Aqueous Solubility, Bioavailability, Photostability, and Permeability" @default.
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• W4297524384 doi "https://doi.org/10.3390/pharmaceutics14102073" @default.
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