https://doi.org/10.15255/KUI.2024.031
Published: Kem. Ind. 73 (13) (2024) 581–590
Paper reference number: KUI-31/2024
Paper type: Original scientific paper
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Enhancing the Release Profile of Drug through Mechanochemical Preparation of Amorphous Solid Dispersions

P. Grobenski, M. Adamić-Golić, P. Klonkay, K. Sokač and K. Žižek

Abstract

Dasatinib (DAS) is a drug used in the treatment of chronic myeloid and acute lymphoblastic leukemia. While DAS exhibits good intestinal permeability, its poor solubility in aqueous medium limits its bioavailability. To enhance DAS’s release profile, solid dispersions of DAS and polyvinylpyrrolidone (PVP), with a DAS mass fraction of 25 %, were prepared mechanochemically in a planetary ball mill under four different process conditions. These solid dispersions were produced without a solvent, following the principles of green chemistry. The solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy to determine the thermal properties and phase composition of the solid dispersions, as well as possible interactions between DAS and PVP. Four types of tablets were prepared, containing: original DAS, mechanochemically treated DAS, a physical mixture of DAS and PVP, and a solid dispersion of DAS and PVP prepared under optimised process conditions. Granules of excipients used in the tablet formulations included mannitol, croscarmellose sodium, and polyethylene glycol. The tablets were tested for uniformity of mass and drug content, hardness, and disintegration properties. DAS release profiles were determined through in vitro dissolution testing. The mechanochemical preparation of amorphous solid dispersions was found to modify the release profile of DAS.

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Keywords

dasatinib, drug property improvement, mechanochemical activation, amorphous solid dispersion, drug release