Chemistry of Solubility and Solutions

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.

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 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.

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.

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).

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.

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.

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.

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.

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.

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.

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.