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  • Title: Inclusion complex of ITH12674 with 2-hydroxypropyl-β-cyclodextrin: Preparation, physical characterization and pharmacological effect.
    Author: Michalska P, Wojnicz A, Ruiz-Nuño A, Abril S, Buendia I, León R.
    Journal: Carbohydr Polym; 2017 Feb 10; 157():94-104. PubMed ID: 27988012.
    Abstract:
    ITH12674 is a multitarget drug, designed to exert a dual "drug-prodrug" mechanism of action, able to induce the phase II antioxidant and anti-inflammatory response for the treatment of brain ischemia. However, its physicochemical properties limit its potential preclinical development due to its low water solubility and instability towards heat and pH variations. In order to improve its properties, we prepared the inclusion complex of ITH12674 with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) by the freeze-drying method. The formation of the inclusion complex was confirmed by FT-IR spectroscopy, PXRD, DSC, 1H NMR and SEM techniques. Experimental results showed that the inclusion complex enhanced its water solubility and stability against heat, acidic and basic conditions. Furthermore, the inclusion complex, prepared in water solution, exerted the same potency to induce the phase II antioxidant response as the pure ITH12674. Thus the formation of the inclusion complex with HP-β-CD is a very effective method to stabilize and solubilize the active compound for its future preclinical development.
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