Authors:

Luke DeLion

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About Paper:

Effective delivery of hydrophobic drugs is challenging due to poor solubility and bioavailability. Vodobatinib (VBN) is a strongly lipophilic, weakly basic drug with low oral bioavailability in its crystalline form. This project aims to adapt an 'amorphous drug polymer salt' formulation strategy for VBN that increases the rate of drug dissolution in vitro. The technique involves dissolving and mixing basic drugs with acidic polymers in an aqueous system to form drug-polymer salts. In this work, we compared poly(styrene sulfonic acid) and poly(acrylic acid) as candidate polymers. Tetrahydrofuran, acetonitrile, and dimethyl sulfoxide were used as solvents to form the aqueous environment, and ethanol and water were incorporated as protic ionic liquids to facilitate acid-base reactions for improved protonation and to ensure high salt formation. We additionally studied the effects of temperature, mixing time, and solvent amount on drug-polymer salt formation. After formulation, vacuum desiccation and heating were used to remove residual solvent, which was quantified using nuclear magnetic resonance (NMR). The degree of salt formation will be evaluated on the dry solid products using X-ray photoelectron spectroscopy. The salt product is predicted to yield higher drug release and improved solubility compared to crystalline VBN in simulated intestinal fluids (in progress). The potential success of this technique offers pharmaceutical manufacturers an alternative method to improve efficacy of small-molecule drugs. Keywords: Vodobatinib; Bioavailability; Amorphous Solid Dispersions; Hydrophobicity; Dissolution Kinetics

Source:

Purdue University / 2024

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Co-authors:

Luke DeLion