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<p>Carvedilol (CARV), an antihypertensive agent employed for managing chronic heart failure, exhibits low oral bioavailability and undergoes extensive first-pass metabolism. With the aim of developing new oral solid dosage forms with enhanced biopharmaceutical profile expected to result in superior bioavailability, cyclodextrin complexation can be employed. This research sought to prepare and characterize two inclusion complexes (ICs) of CARV with two functionalized <i>β</i>-cyclodextrins, namely randomly methylated <i>β</i>-cyclodextrin (RM-<i>β</i>-CD) and heptakis(2,6-di-O-methyl)-<i>β</i>-cyclodextrin (DM-<i>β</i>-CD), respectively. The stoichiometry of the ICs and the values of the stability constants were determined by applying phase solubility studies, the Job’s method and the Benesi–Hildebrand model. Analyses revealed a higher value of stability constant for CARV/DM-<i>β</i>-CD, and a molar ratio of 1:1 for both ICs. CARV solubility after complexation has been evaluated by means of saturation solubility studies which highlighted an increase in solubility by 26.47-fold when DM-<i>β</i>-CD was used. In solid state, the ICs were characterized by thermal methods, universal-attenuated total reflectance Fourier-transform infrared spectroscopy (UATR-FTIR) and powder X-ray diffractometry (PXRD). Molecular modeling studies were also carried out for obtaining information over the intermolecular interactions that took place inside the guest–host structure. Outcomes of the study indicated that CARV when encapsulated in DM-<i>β</i>-CD cavity showed superior efficacy in improving the solubility profile. The ICs of CARV with both DM-<i>β</i>-CD and RM-<i>β</i>-CD allowed an enhancement of drug solubility, accordingly, the obtained supramolecular adduct might be the starting point for further research aiming to design a new pharmaceutical formulation that includes CARV with greatly pharmaceutical profile.</p>

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Host–guest inclusion complexes of carvedilol with methylated β-cyclodextrins

  • 期刊论文

  • 发表日期：

    2025年12月10日

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  • Ema Niţu,
  • Ioana Mitrofan,
  • Luciana Buliga,
  • Amalia Ridichie,
  • Carmen Tomoroga,
  • Cornelia Muntean,
  • Gerlinde Rusu,
  • Renata Văruţ,
  • Adriana Ledeţi,
  • Ionuţ Ledeţi,
  • Laura Sbârcea

摘要

Carvedilol (CARV), an antihypertensive agent employed for managing chronic heart failure, exhibits low oral bioavailability and undergoes extensive first-pass metabolism. With the aim of developing new oral solid dosage forms with enhanced biopharmaceutical profile expected to result in superior bioavailability, cyclodextrin complexation can be employed. This research sought to prepare and characterize two inclusion complexes (ICs) of CARV with two functionalized β-cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), respectively. The stoichiometry of the ICs and the values of the stability constants were determined by applying phase solubility studies, the Job’s method and the Benesi–Hildebrand model. Analyses revealed a higher value of stability constant for CARV/DM-β-CD, and a molar ratio of 1:1 for both ICs. CARV solubility after complexation has been evaluated by means of saturation solubility studies which highlighted an increase in solubility by 26.47-fold when DM-β-CD was used. In solid state, the ICs were characterized by thermal methods, universal-attenuated total reflectance Fourier-transform infrared spectroscopy (UATR-FTIR) and powder X-ray diffractometry (PXRD). Molecular modeling studies were also carried out for obtaining information over the intermolecular interactions that took place inside the guest–host structure. Outcomes of the study indicated that CARV when encapsulated in DM-β-CD cavity showed superior efficacy in improving the solubility profile. The ICs of CARV with both DM-β-CD and RM-β-CD allowed an enhancement of drug solubility, accordingly, the obtained supramolecular adduct might be the starting point for further research aiming to design a new pharmaceutical formulation that includes CARV with greatly pharmaceutical profile.