Chemistry of Solubility and Solutions

Questions and Answers

What is the qualitative definition of solubility?

Spontaneous interaction of two or more substances to form a homogenous molecular dispersion.

How is dissolution defined?

The transfer of molecules or ions from a solid state into solution.

Solubility of gases in liquids decreases with an increase in temperature.

True

Solubility of ___ in liquids is more commonly referred to as miscibility rather than solubility.

liquids Signup and view all the answers

What is the purpose of using co-solvents to improve the solubility of drugs?

To reduce the difference in polarity between drugs and water/co-solvent systems, thereby improving solubility. Signup and view all the answers

Which of the following are examples of weak bonds involved in complexation for improving drug solubility? (Select all that apply)

Hydrogen bonding Signup and view all the answers

What is the purpose of water soluble prodrugs in enhancing drug solubility?

To increase the amount of active drug reaching the site of action through physicochemical and pharmacokinetic manipulation. Signup and view all the answers

Dissolution is a process independent of time and a constant at constant conditions.

True Signup and view all the answers

The _ is the proportionality constant in the Noyes-Whitney equation for dissolution rate.

diffusion coefficient Signup and view all the answers

Study Notes

Solutions and Solubility

A dispersed system is a heterogeneous system consisting of one component (dispersed phase) distributed throughout another component (dispersion medium or continuous phase).
Based on the size of the dispersed phase, there are three types of dispersed systems:
- Solution: a mixture of two or more components forming a homogeneous molecular dispersion.
- Colloid: a mixture of particles with sizes between 1-100 nm.
- Suspension: a mixture of particles with sizes larger than 100 nm.

Dissolution Process

The transfer of molecules or ions from a solid state into a solution is known as dissolution.
The dissolution process can be represented by the equation: Solute + Solvent → Solution.
The spontaneous interaction between two or more substances to form a homogeneous molecular dispersion is known as solubility.

Qualitative and Quantitative Solubility

Qualitative definition of solubility: the ability of a substance to dissolve in another substance to form a homogeneous molecular dispersion.
Quantitative definition of solubility: the amount of solute that passes into solution when equilibrium is established between the solute in solution and the excess undissolved solute at a constant temperature.

Types of Solutions

Saturated solution: a solution in which the dissolved solute is in equilibrium with the undissolved solute at a definite temperature.
Unsaturated solution: a solution in which the concentration of dissolved solute is less than that necessary for complete saturation at a definite temperature.
Supersaturated solution: a solution in which the concentration of dissolved solute is more than that necessary for complete saturation at a definite temperature.

Methods of Expressing Solubility

Qualitative description: using descriptive terms such as very soluble, freely soluble, soluble, sparingly soluble, slightly soluble, and very slightly soluble.
Quantitative description: using concentration terms such as molarity (M), percent weight in volume (%w/v), and volume percent (%v/v).

Types of Solubility

Solubility of gases in liquids: the concentration of the dissolved gas when it is in equilibrium with some of the pure gas above the solution.
Solubility of solids in liquids: the ability of a solid to dissolve in a liquid.
Solubility of liquids in liquids: the ability of a liquid to dissolve in another liquid.

Factors Affecting Solubility of Gas in Liquid

Pressure: the concentration of the dissolved gas is proportional to the partial pressure of the gas above the solution (Henry's law).
Temperature: the solubility of gases in liquids decreases with an increase in temperature.

Solubility of Solid in Liquid

Mechanism of solute-solvent interactions: polar solvents (e.g., water, ethanol, glycerol) dissolve polar solutes through dipole interaction and hydrogen bond formation, while non-polar solvents (e.g., benzene, mineral oil) dissolve non-polar solutes by weak Van der Waals forces.

Factors Affecting Solubility of Solid in Liquid

Temperature: the solubility of solids in liquids is affected by temperature, with some solids having an endothermic, exothermic, or isothermic process.
pH: the solubility of weak acids and bases is affected by pH, with ionization increasing solubility in water.
Particle size: a decrease in particle size increases the surface area, which can increase solubility.
Crystal structure: amorphous forms of drugs are more soluble than crystalline forms.
Molecular structure: changes in molecular structure can affect solubility, such as salt formation, esterification, and addition of polar groups.

Methods to Improve Solubility of Drugs

Use of co-solvents: a co-solvent is a water-miscible organic solvent that can reduce the difference in polarity between the drug and water, improving solubility.
Complexation: a reversible association between two or more molecules to form a non-bonded product with a well-defined stoichiometry.
Water-soluble prodrugs: pharmacologically inactive derivatives of active drugs that can be converted into active drugs within the body.
Solubilization using surfactants: surfactants can reduce the surface tension of the solvent, allowing for better solubility of the drug.

Dissolution vs. Dissolution Rate

Solubility: the saturation process independent of time, which is a physical property that is constant at constant conditions.
Dissolution: the process by which a solid goes into solution.
Dissolution rate: the rate at which a solute goes into solution, which is dependent on the stagnant layer, diffusion coefficient, and concentration gradient.

Dissolution Theory

The stagnant layer is a thin layer of solvent surrounding the solid particle, which is saturated with the dissolved solute.
The dissolution rate is dependent on the slowest step, which is the diffusion of the dissolved solute through the stagnant layer.
The Noyes-Whitney equation describes the dissolution rate of a solid: Dissolution Rate (dm/dt) = DA (Cs - C)/L.