ArticlePharmaceutical research2015
Using Environment-Sensitive Fluorescent Probes to Characterize Liquid-Liquid Phase Separation in Supersaturated Solutions of Poorly Water Soluble Compounds.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Effect of Polymer-stabilized Liquid-liquid Phase Separation on the Permeability Across the Corneal Barrier.AAPS PharmSciTech · 2026Article
- Mechanisms and Extent of Enhanced Passive Permeation by Colloidal Drug Particles.Molecular pharmaceutics · 2022Article
- Recent Advances in Enhancement of Dissolution and Supersaturation of Poorly Water-Soluble Drug in Amorphous Pharmaceutical Solids: A Review.AAPS PharmSciTech · 2021Review
- Drug-Rich Phases Induced by Amorphous Solid Dispersion: Arbitrary or Intentional Goal in Oral Drug Delivery?Pharmaceutics · 2021Review
- Amorphous Solid Dispersions Containing Residual Crystallinity: Competition Between Dissolution and Matrix Crystallization.The AAPS journal · 2021Article
- A Crowding Barrier to Protein Inhibition in Colloidal Aggregates.Journal of medicinal chemistry · 2021Article
- Characterization of Phase Transformations for Amorphous Solid Dispersions of a Weakly Basic Drug upon Dissolution in Biorelevant Media.Pharmaceutical research · 2019Article
- The Effect of Promiscuous Aggregation on in Vitro Drug Metabolism Assays.Pharmaceutical research · 2019Article
- Article
- Phase Behavior of Ritonavir Amorphous Solid Dispersions during Hydration and Dissolution.Pharmaceutical research · 2017Article
- Insights into Nano- and Micron-Scale Phase Separation in Amorphous Solid Dispersions Using Fluorescence-Based Techniques in Combination with Solid State Nuclear Magnetic Resonance Spectroscopy.Pharmaceutical research · 2017Article
- Internal Structure and Preferential Protein Binding of Colloidal Aggregates.ACS chemical biology · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeHighly 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.
methodsSix different environment-sensitive fluorophores were employed to study LLPS in highly supersaturated solutions of several model compounds, all dihydropyridine derivatives.
resultsEach 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.
conclusionsEnvironment-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.
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