ArticleMolecular pharmaceutics2024
Kinetic and Thermodynamic Interplay of Polymer-Mediated Liquid-Liquid Phase Separation for Poorly Water-Soluble Drugs.
Article in Molecular pharmaceutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Entropy-Regulated Swelling as the Mechanistic Driver of Drug Diffusion in a Mechanically Robust Hydroxyapatite/PVA Hybrid Hydrogel.Macromolecules · 2026Article
- Combining High-Throughput Screening and Machine Learning to Predict the Formation of Both Binary and Ternary Amorphous Solid Dispersion Formulations for Early Drug Discovery and Development.Pharmaceutical research · 2025Article
- Mechanistic Insights into Amorphous Solid Dispersions: Bridging Theory and Practice in Drug Delivery.Pharmaceutical research · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
Understanding the interplay between kinetics and thermodynamics of polymer-mediated liquid-liquid phase separation is crucial for designing and implementing an amorphous solid dispersion formulation strategy for poorly water-soluble drugs. This work investigates the phase behaviors of a poorly water-soluble model drug, celecoxib (CXB), in a supersaturated aqueous solution with and without polymeric additives (PVP, PVPVA, HPMCAS, and HPMCP). Drug-polymer-water ternary phase diagrams were also constructed to estimate the thermodynamic behaviors of the mixtures at room temperature. The liquid-liquid phase separation onset point for CXB was detected using an inline UV/vis spectrometer equipped with a fiber optic probe. Varying CXB concentrations were achieved using an accurate syringe pump throughout this study. The appearance of the transient nanodroplets was verified by cryo-EM and total internal reflection fluoresence microscopic techniques. The impacts of various factors, such as polymer composition, drug stock solution pumping rates, and the types of drug-polymer interactions, are tested against the onset points of the CXB liquid-liquid phase separation (LLPS). It was found that the types of drug-polymer interactions, i.e., hydrogen bonding and hydrophobic interactions, are vital to the position and shapes of LLPS in the supersaturation drug solution. A relation between the behaviors of LLPS and its location in the CXB-polymer-water ternary phase diagram was drawn from the findings.
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