Using Environment-Sensitive Fluorescent Probes to Characterize Liquid-Liquid Phase Separation in Supersaturated Solutions of Poorly Water Soluble Compounds

Raina, Shweta; Alonzo, David; Zhang, Geoff; Gao, Yi; Taylor, Lynne
November 2015
Pharmaceutical Research;Nov2015, Vol. 32 Issue 11, p3660
Academic Journal
Purpose: Highly supersaturated aqueous solutions of poorly soluble compounds can undergo liquid-liquid phase separation (LLPS) when the concentration exceeds the 'amorphous solubility'. This phenomenon has been widely observed during high throughput screening of new molecular entities as well as during the dissolution of amorphous solid dispersions. In this study, we have evaluated the use of environment-sensitive fluorescence probes to investigate the formation and properties of the non-crystalline drug-rich aggregates formed in aqueous solutions as a result of LLPS. Methods: Six different environment-sensitive fluorophores were employed to study LLPS in highly supersaturated solutions of several model compounds, all dihydropyridine derivatives. Results: Each fluoroprobe exhibited a large hypsochromic shift with decreasing environment polarity. Upon drug aggregate formation, the probes partitioned into the drug-rich phase and exhibited changes in emission wavelength and intensity consistent with sensing a lower polarity environment. The LLPS onset concentrations determined using the fluorescence measurements were in good agreement with light scattering measurements as well as theoretically estimated amorphous solubility values. Conclusions: Environment-sensitive fluorescence probes are useful to help understand the phase behavior of highly supersaturated aqueous solutions, which in turn is important in the context of developing enabling formulations for poorly soluble compounds.


Related Articles

  • Effect of molecular weight on the dissolution properties of polystyrene latex films. Ugur, Saziye; Dinc, Atilla; Kislak, Yusuf // Journal of Polymer Research;Sep2012, Vol. 19 Issue 9, p1 

    An in situ steady-state fluorescence (SSF) technique was applied in order to study the dissolution process of polystyrene (PS) latex films. The effect of the molecular weight M of the PS on the dissolution rate was investigated. The PS chains were copolymerized with (1-pyrene)methyl methacrylate...

  • An Instrument-Based Screening Assay for DNA-Targeted Anticancer Drugs Using Resonance Light Scattering. Zhanguang Chen; Guoliang Liu; Maohuai Chen; Xi Chen; Mingyao Wu; Xingtong Chen // Combinatorial Chemistry & High Throughput Screening;Jun2010, Vol. 13 Issue 5, p383 

    DNA is a valid drug target for development of target-based therapeutics against cancer. Screening DNA-targeted anticancer drugs is a key process for the research and development of new anticancer drugs. The traditional anticancer drug screening methods, including animal experiments and...

  • Deformations and overlap of instability zones in the Mathieu–Hill equation. Grigor’ev, A. I.; Golovanov, A. S. // Technical Physics Letters;Oct99, Vol. 25 Issue 10, p806 

    A numerical analysis of the Mathieu-Hill equation describing the time evolution of the amplitudes of capillary waves at the interface between two liquids, the upper moving relative to the denser lower liquid at a time-dependent velocity, is used to show that for certain values of the...

  • Interaction of a polymer chain with an asymmetric liquid–liquid interface. Wang, Zhen-Gang; Nemirovsky, A. M.; Freed, Karl F. // Journal of Chemical Physics;9/1/1986, Vol. 85 Issue 5, p3068 

    A continuum model is presented for polymer chains near an asymmetric (A–B) liquid–liquid interface where each side of the interface can have different polymer–surface interactions. For example, one side can attract the macromolecule, while the other can repel it. The model...

  • Pervaporation -- A novel process for liquid -liquid separation. Singh, Manohar; Kumar, Vinay // Chemical Business;Sep2002, Vol. 16 Issue 9, p36 

    Presents information on the pervaporation process for liquid-liquid separation. Types of membranes and their functions; Factors affecting the membrane performance; Characteristics of pervaporation.

  • Entropy of melting: Its effect on the liquid-liquid phase change of carbon. van Thiel, Mathias; Ree, Francis H. // Journal of Applied Physics;5/1/1995, Vol. 77 Issue 9, p4804 

    Provides information on a study which investigated the possibility oof the elimination of the liquid-liquid phase change of carbon through smooth pressure dependence. Methods; Results and discussion; Conclusions.

  • When liquids stay dry. Dell'Aversana, Pasquale; Neitzel, G. Paul // Physics Today;Jan98, Vol. 51 Issue 1, p38 

    Provides information on the temporary noncoalescence of two bodies of the same liquid. Intriguing applications offered by noncoalescence; Demonstrating noncoalescence; Potential technological applications of noncoalescence. INSET: On the floating of drops on the surface of water depending....

  • Influence of the supporting electrolyte in the properties of liquid-liquid interfaces. Nata´lia, M.; Cordeiro, D. S.; Fernandes, Pedro A.; Gomes, Jose´ A. N. F. // AIP Conference Proceedings;2001, Vol. 574 Issue 1, p254 

    © 2001 American Institute of Physics.

  • Size distribution and critical supersaturation spectrum of the aerosol from an electrically heated nichrome wire. Trueblood, Max B.; Carter, Millard A.; Hagen, Donald E.; Whitefield, Philip D.; Podzimek, Josef // AIP Conference Proceedings;2000, Vol. 534 Issue 1, p873 

    An aerosol generator was constructed that produces particles from the Joule heating of a nichrome wire. This novel generator produced a stable output (+/- 20%) over a 7 hour period. The approximate mean diameter was 24 nm. The critical supersaturation spectrum was measured and found to be quite...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics