Authors:

Luke DeLion

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About Paper:

Vodobatinib (VBN) is a very weakly basic, anticancer treatment with low oral bioavailability and poor enteric solubility. Polymeric amorphization techniques offer viable approaches to improving such biopharmaceutical properties. In this work, we demonstrate that an emerging salt synthesis method called slurry conversion can successfully produce multiple amorphous drug-polymer salts with enhanced dissolution rates. Two acidic polymers, polystyrene sulfonic acid (PSSA) and polyacrylic acid (PAA), were individually evaluated for salt formation with VBN. Each formulation involved mixing the drug and polymer in a 1:2 (v/v) ratio of protic liquid to solvent and a 1:9 (w/w) solid to solvent ratio. The mixtures were stirred at elevated temperatures, then dried with vacuum heating to yield amorphous salts. Tetrahydrofuran and acetonitrile served as solvents, while ultra-pure water and ethanol were used as protic liquids to facilitate acid-base interactions. Drug loadings at 10%, 20%, and 40% were tested, with most slurries exhibiting complete dissolution and amorphization during mixing. In biorelevant fluid, in vitro testing revealed significantly faster dissolution rates compared to crystalline VBN and a hot-melt extrude formulation. 1H NMR spectroscopy indicated residual solvent remained after drying, highlighting areas for improvement. For effective salt formation, protonation of the quinoline nitrogen atoms on VBN is expected to occur, which can be confirmed by X-ray photoelectron spectroscopy. Additionally, the amorphous characteristic of each salt will be analyzed using X-ray powdered diffraction. Overall, slurry conversion is a potential alternative for very weakly basic drugs that provides excellent dissolution profiles. Keywords: Amorphous Drug-Polymer Salt; Vodobatinib; Polyelectrolytes; Dissolution; Bioavailability

Source:

Purdue University / 2025

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Co-authors:

Luke DeLion