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<p>The work aims to improve the solubility and dissolution rate of the cardiovascular drug carvedilol (CVD) of II class BCS by a co-crystallization approach. The slurry method was used to preparation of CVD cocrystals. The existence of new solid phases was confirmed by PXRD, DSC, TGA, FTIR and UV–vis spectroscopy. The dissolution kinetics of two component systems in a model buffer solution was studied by the classical shake flask method. The process of CVD release from co-crystals tablets were studied in accordance with Pharmacopoeia standard using a dissolution tester. Pharmaceutical cocrystals of CVD with two coformers, 2-hydroxybenzamide (2OHBZA) and 4-hydroxybenzamide (4OHBZA) in molar ratio 1:1, have been obtained for the first time. Thermodynamic characteristics of the cocrystallization reaction of the active pharmaceutical ingredient with the selected coformers have been experimentally determined for the synthesized CVD/2OHBZA and CVD/4OHBZA cocrystals. It has been shown that the process of cocrystal formation is enthalpy-determined, which is typical for most two-component crystals. Kinetic solubility profiles of new solid phases have been determined in a buffer solution pH 7.4, simulating the pH of blood plasma. It was found that the equilibrium solubility of co-crystal forms of carvedilol significantly exceeds the solubility of original drug. <i>In vitro</i> study of the release of CVD from co-crystal tablets showed a improving of the drug release rate into solution to 67% for CVD/2OHBZA and 43% for CVD/4OHBZA, that by 2.6 and 1.7 times higher then the raw drug. Considering the significant enhancement of carvedilol solubility in two-component systems and their stability in aqueous medium, co-crystallization is a promising approach for the development of new dosage forms of this drug with improved bioavailability.</p> Graphical Abstract <p></p>

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Carvedilol Pharmaceutical Cocrystals: Preparation, Advanced Characterization and Dissolution Behavior

  • 期刊论文

  • 发表日期：

    2026年1月21日

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  • Angelica Sharapova,
  • Marina Ol’khovich,
  • Svetlana Blokhina

摘要

The work aims to improve the solubility and dissolution rate of the cardiovascular drug carvedilol (CVD) of II class BCS by a co-crystallization approach. The slurry method was used to preparation of CVD cocrystals. The existence of new solid phases was confirmed by PXRD, DSC, TGA, FTIR and UV–vis spectroscopy. The dissolution kinetics of two component systems in a model buffer solution was studied by the classical shake flask method. The process of CVD release from co-crystals tablets were studied in accordance with Pharmacopoeia standard using a dissolution tester. Pharmaceutical cocrystals of CVD with two coformers, 2-hydroxybenzamide (2OHBZA) and 4-hydroxybenzamide (4OHBZA) in molar ratio 1:1, have been obtained for the first time. Thermodynamic characteristics of the cocrystallization reaction of the active pharmaceutical ingredient with the selected coformers have been experimentally determined for the synthesized CVD/2OHBZA and CVD/4OHBZA cocrystals. It has been shown that the process of cocrystal formation is enthalpy-determined, which is typical for most two-component crystals. Kinetic solubility profiles of new solid phases have been determined in a buffer solution pH 7.4, simulating the pH of blood plasma. It was found that the equilibrium solubility of co-crystal forms of carvedilol significantly exceeds the solubility of original drug. In vitro study of the release of CVD from co-crystal tablets showed a improving of the drug release rate into solution to 67% for CVD/2OHBZA and 43% for CVD/4OHBZA, that by 2.6 and 1.7 times higher then the raw drug. Considering the significant enhancement of carvedilol solubility in two-component systems and their stability in aqueous medium, co-crystallization is a promising approach for the development of new dosage forms of this drug with improved bioavailability.

Graphical Abstract