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  • Investigating the effect of...
    Sokač, Katarina; Priselec, Paula; Barač, Jelena; Bafti, Arijeta; Taradi, Filip; Žižek, Krunoslav

    Journal of applied polymer science, July 15, 2024, Volume: 141, Issue: 27
    Journal Article

    Dasatinib (DAS) is a second‐generation tyrosine kinase inhibitor used in the treatment of Philadelphia chromosome‐positive chronic myeloid leukemia and acute lymphoblastic leukemia. Nevertheless, this drug is hindered by poor gastrointestinal absorption and limited bioavailability, primarily attributable to its low aqueous solubility. To improve its properties, solid dispersions of DAS within a matrix of the hydrophilic polymer polyvinylpyrrolidone (PVP) are prepared by cogrinding in a vibrational ball mill at various drug‐to‐polymer ratios. The prepared solid dispersions are thoroughly characterized by several methods to verify the drug's amorphization and enhanced wettability as a result of successful mechanochemical activation. Fluidized bed melt granulation and traditional tableting are used to prepare tablets of 8 mm diameter with strictly defined aimed properties. Characterization of tablets includes testing their hardness, disintegration, and in vitro dissolution. The in vitro release profiles reveal a significant improvement in the release rate of DAS from tablets containing solid dispersion with the highest polymer ratio when compared with those containing untreated DAS or solid dispersions with a low polymer ratio. The results confirm the significant effect of the PVP ratio in solid dispersions on the surface characteristics and dissolution rate of DAS. Tablets containing a solid dispersion of DAS:PVP 1:3 exhibit a significant increase in the release rate of DAS and its hydrophilicity. These findings emphasize the potential of using solid dispersions with PVP as a promising strategy to enhance the in vitro dissolution of poorly soluble drugs. This could ultimately lead to improved oral absorption and, consequently, enhance the drug's bioavailability.