Dissolution is the process where a solute in gaseous, liquid, or solid phase dissolves in a solvent to form a solution.
Solubility
Solubility is the maximum concentration of a solute that can dissolve in a solvent at a given temperature. At the maximum concentration of solute, the solution is said to be saturated. The units of solubility can be provided in mol/L or g/L.
Factors that affect solubility include:
Dissolution
The rate of dissolution is represented by the Noyes-Whitney equation: dm/dt = D*A*(Cs - C)/h
Where:
Solubility
Temperature
Effect of temperature on liquid and solid solutes
As temperature increases, the solubility of a solid or liquid can fluctuate depending on whether the dissolution reaction is exothermic or endothermic.
Increasing solubility with increasing temperature
Decreasing solubility with increasing temperature
Effect of temperature on gas solutes
In general, heat energy is released as gas dissolves in solution, meaning the dissolution reaction is exothermic. As such, a gas becomes less soluble as temperate increases.
Increasing temperature results in increased kinetic energy. Gas molecules with greater kinetic energy move more rapidly resulting in the intermolecular bonds between the gas solute and solvent breaking.
Pressure: Henry’s law
The solubility of gas is affected by changes in pressure on the system. A gas dissolves in liquids to form solutions. This results in equilibrium in the system where a proportion of gas molecules is dissolved in liquid while the rest remains in gaseous phase above the liquid.
Henry’s law states that: “At constant temperature, the amount of gas that dissolves in a volume of liquid is proportional to the partial pressure of the gas in equilibrium with the liquid.”
Henry's law results in the following equation: C = kP
Where:
Hence as the pressure of the gas above the liquid in the system increases, the gas molecules become more soluble in the solvent. Likewise, if the pressure of the gas in the system decreases, gas becomes less soluble in the solvent.
Limitations of Henry’s Law on gas solubility:
Dissolution
Methods to enhance dissolution to improve oral bioavailability include: [4][5][6]
Le Chatelier’s principle:
If stressors like pressure and heat are applied to the equilibrium, the system will respond by adjusting to minimize the effects of the stress.
For example, if pressure is applied to a system, the dissolution reaction will respond to minimize this stress by reducing the pressure in the system.
Heat of solution
Solids and liquids form as a result of individual particles being held together by inter-particulate bonds. To form a solution, energy is required to break the bonds between the particles within the solid or liquid. Heat energy is also required to break the bonds in a solvent to insert one of the molecules into the solution. Both of these processes are endothermic. Heat energy is released when the solute molecules form bonds with the solvent molecules i.e. this process is exothermic.
Depending on whether more energy is used to break the bonds within the solute and solvent or is released when new bonds are formed between the solute and solvent, the reaction overall can be exothermic or endothermic.
The total amount of heat energy released from or absorbed by the system = sum of heat energy absorbed when bonds are broken – the sum of heat energy released when bonds are formed
Application of Henry’s Law: Decompression Sickness
Henry’s Law explains the phenomena of decompression sickness. When scuba divers submerge themselves in deep water, the pressure of the water increases the pressure in their bodies. Nitrogen, a gas in our blood, dissolves under the increased pressure. Nitrogen is physiologically inert, so it is not used in tissue metabolism. If the scuba diver ascends to the surface too quickly, the rapid drop in pressure decreases the solubility of nitrogen, causing nitrogen bubbles to come out of solution. The nitrogen bubbles can form painful and potentially fatal gas embolisms.
Dissolution
Dissolution is important for health practitioners because, for drugs to be absorbed and have a physiological effect in the human body, they must be in solution. For solid preparations, such as tablets and suppositories, the rate of dissolution affects how fast a drug is absorbed in the body.
Solubility
Aqueous solubility is often considered when formulating drugs. Poorly soluble formulations provide difficulties in the development of pharmaceuticals. Chloramphenicol, phenytoin, and digoxin are some examples. Drugs, particularly those for oral administration, may have poor aqueous solubility. This may result in low bioavailability leading to insufficient exposure and physiologic effect in the body.
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