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Related Concept Videos

Physical Properties Affecting Solubility02:19

Physical Properties Affecting Solubility

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Solutions of Gases in Liquids
As for any solution, the solubility of a gas in a liquid is affected by the attractive intermolecular forces between solute and solvent species. Unlike solid and liquid solutes, however, there is no solute-solute intermolecular attraction to overcome when a gaseous solute dissolves in a liquid solvent since the atoms or molecules comprising a gas are far separated and experience negligible interactions. Consequently, solute-solvent interactions are the sole...
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Solubility Equilibria: Overview01:09

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When a substance such as sodium chloride is added to water, it dissolves, forming an aqueous solution. The extent of dissolution is called solubility. The process of dissolution can exist in equilibrium, just like other chemical processes. Solubility equilibria are also called precipitation equilibria because the process of solubility can be reversible. The reverse of the solubility process is called precipitation.
Solubility is important in biological and environmental processes. A notable...
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Chemical and Solubility Equilibria02:21

Chemical and Solubility Equilibria

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The free energy change associated with dissolving a solute in a liter of solvent is called the free energy of a solution, ΔGsolution. The overall ΔGsolution is expressed as the balance of ΔGinteraction against the always-favorable free-energy of mixing, ΔGmixing. Solution formation is favorable if  ΔGsolution is less than zero, whereas it is unfavorable if ΔGsolution is greater than zero. In short, for a solution to form and complete dissolution to take place,...
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Enthalpy of Solution02:39

Enthalpy of Solution

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There are two criteria that favor, but do not guarantee, the spontaneous formation of a solution:
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Entropy and Solvation02:05

Entropy and Solvation

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The process of surrounding a solute with solvent is called solvation. It involves evenly distributing the solute within the solvent. The rule of thumb for determining a solvent for a given compound is that like dissolves like. A good solvent has molecular characteristics similar to those of the compound to be dissolved. For example, polar solutions dissolve polar solutes, and apolar solvents dissolve apolar solutes. A polar solvent is a solvent that has a high dielectric constant (ϵ...
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Solution Formation02:16

Solution Formation

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There is no one solvent that can dissolve every type of solute. Some substances that readily dissolve in a certain solvent might be insoluble in a different solvent. A simple way to predict which substances dissolve in which solvent is the phrase "like dissolves like". This means that polar substances, such as salt and sugar, dissolve in a polar substance like water. In contrast, non-polar substances are more soluble in non-polar solvents such as carbon tetrachloride.
This selective...
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Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis
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Thermodynamic solubility measurement without chemical analysis.

Emma Hokkala1, Clare J Strachan1, Mikael Agopov2

  • 1Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E 00790, Helsinki, Finland.

International Journal of Pharmaceutics
|February 12, 2024
PubMed
Summary

Single particle analysis (SPA) offers a faster, more efficient method for determining pharmaceutical compound solubility compared to traditional shake-flask (SF) methods. SPA significantly reduces experiment time from days to hours, requiring fewer resources for diverse chemical analyses.

Keywords:
DissolutionHPLCMass spectrometryOptical imagingRefractometrySingle particle analysisSolubility

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Area of Science:

  • Pharmaceutical Science
  • Analytical Chemistry
  • Materials Science

Background:

  • Solubility determination is crucial for pharmaceutical development.
  • Traditional methods like shake-flask (SF) are time-consuming and resource-intensive.
  • Analyzing diverse pharmaceutical compounds requires multiple analytical techniques.

Purpose of the Study:

  • To compare the efficacy of single particle analysis (SPA) with the gold standard shake-flask (SF) method for solubility determination.
  • To evaluate SPA's ability to analyze a wide range of pharmaceutical compounds with limited resources.
  • To assess the time and resource efficiency of SPA versus SF methods.

Main Methods:

  • Comparison of optical imaging-based single particle analysis (SPA) with the shake-flask (SF) method.
  • Analysis of pharmaceutical compounds spanning 7 log units in solubility.
  • Utilized techniques including HPLC-UV, LC-MS, refractometry, and UV-Vis spectrometry for SF method validation.

Main Results:

  • Single particle analysis (SPA) successfully analyzed all tested compounds, unlike traditional methods requiring multiple techniques.
  • SPA experiments were completed in minutes, drastically reducing total experiment time from days to under three hours.
  • An average relative difference of 37% was observed between SPA and SF methods, which is considered good given solubility's inherent variability.

Conclusions:

  • Single particle analysis (SPA) is a highly efficient and effective method for determining the solubility of diverse pharmaceutical compounds.
  • SPA offers significant advantages in terms of speed and resource utilization compared to conventional shake-flask methods.
  • Further research should address challenges in SPA for large particles, fast-dissolving compounds, and density-related inaccuracies.