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Related Concept Videos

Solubility Equilibria: Overview01:09

Solubility Equilibria: Overview

936
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...
936
Factors Affecting Solubility04:01

Factors Affecting Solubility

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Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Chȃtelier’s principle. Consider the dissolution of silver iodide:
34.1K
Solubility Equilibria03:07

Solubility Equilibria

53.5K
Solubility equilibria are established when the dissolution and precipitation of a solute species occur at equal rates. These equilibria underlie many natural and technological processes, ranging from tooth decay to water purification. An understanding of the factors affecting compound solubility is, therefore, essential to the effective management of these processes. This section applies previously introduced equilibrium concepts and tools to systems involving dissolution and precipitation.
The...
53.5K
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH01:21

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

2.1K
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
2.1K
Physical Properties Affecting Solubility02:19

Physical Properties Affecting Solubility

23.9K
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...
23.9K
Chemical and Solubility Equilibria02:21

Chemical and Solubility Equilibria

4.3K
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,...
4.3K

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Related Experiment Video

Updated: Sep 28, 2025

A New Straightforward Method for Lipophilicity logP Measurement using 19F NMR Spectroscopy
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A New Straightforward Method for Lipophilicity logP Measurement using 19F NMR Spectroscopy

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Perspectives in solubility measurement and interpretation.

Christel A S Bergström1, Alex Avdeef2

  • 1Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23 Uppsala, Sweden.

ADMET & DMPK
|March 30, 2022
PubMed
Summary

This study explores drug solubility, highlighting how pH affects ionizable molecules and discussing factors like supersaturation and complexation for better measurement and understanding of drug behavior in suspensions.

Keywords:
Henderson-Hasselbalch equationSolubility-pHdrug aggregatesdrug saltsintrinsic solubilitypharmaceutical cocrystalspre-nucleation clustersshake-flask solubilitysupersaturationthermodynamic solubility

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Area of Science:

  • Pharmaceutical Science
  • Physical Chemistry
  • Drug Discovery

Background:

  • Accurate solubility measurement is crucial for drug development and formulation.
  • Traditional models like the Henderson-Hasselbalch equation may not fully capture complex solubility behaviors of ionizable molecules.
  • Understanding solution equilibria and solid-state properties is key to predicting and controlling drug solubility.

Purpose of the Study:

  • To summarize key aspects of solubility measurement and interpretation, focusing on pH-dependent solubility.
  • To illustrate deviations from predicted solubility-pH curves and explore their underlying causes.
  • To enhance understanding of solution chemistry relevant to drug suspensions and improve assay design.

Main Methods:

  • Review and case study analysis of published solubility determinations as a function of pH.
  • Discussion of limitations in kinetic solubility measurements.
  • Exploration of advanced concepts such as supersaturation, pre-nucleation clusters, and hydrotropic solubilization.

Main Results:

  • Ionizable molecules can exhibit solubility-pH curves that deviate from predictions based on the Henderson-Hasselbalch equation.
  • Factors like drug-buffer complexation, hydrotropy, and cocrystal formation influence solubility.
  • Supersaturation phenomena are linked to pre-nucleation clusters and sub-micellar aggregates.

Conclusions:

  • A deeper understanding of solution equilibria and factors influencing solubility is essential for robust drug development.
  • Improved assay design and data quality assessment are needed for reliable solubility measurements.
  • Recognizing deviations from simple models and considering complex solution phenomena can lead to better drug formulations.