The kinetic and thermodynamic interplay of polymer-mediated liquid-liquid phase separation for poorly water-soluble drugs

Kaijie Qian, Lorenzo Stella, Fanjun Liu, David Jones, Gavin Andrews, Yiwei Tian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding the interplay between kinetics and thermodynamics of polymermediated liquid-liquid phase separation is crucial for designing and implementing theamorphous solid dispersion formulation strategy for poorly water-soluble drugs. Thiswork investigates the phase behaviours of a poorly water-soluble model drug,celecoxib (CCB), in a supersaturated aqueous solution with and without polymericadditives (PVP, PVPVA, HPMCAS, and HPMCP). Drug-polymer-water ternary phasediagrams were also constructed to estimate the thermodynamic behaviours of themixtures at room temperature. The liquid-liquid phase separation onset point for CCBwas detected using an inline UV/Vis spectrometer equipped with a fibre optic probe.Varying CCB concentrations were achieved using an accurate syringe pumpthroughout this study. The impacts of various factors, such as polymer composition,drug stock solution pumping rates, and the types of drug-polymer interaction, aretested against the onset points of the CCB liquid-liquid phase separation (LLPS). Itwas found that the types of drug-polymer interaction, i.e., hydrogen bonding andhydrophobic interaction, are vital to the position and shapes of LLPS in thesupersaturation drug solution. A relation between the behaviours of LLPS and itslocation in the CCB-polymer-water ternary phase diagram was drawn from the findings.
Original languageEnglish
JournalMolecular Pharmaceutics
Publication statusAccepted - 05 Mar 2024

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