# Biochemistry, Dissolution and Solubility

Article Author:
Jue Xi Lu
Article Editor:
John Murray
Updated:
4/29/2019 10:52:50 PM
Biochemistry, Dissolution and Solubility

## Introduction

Dissolution [1][2][3][2]

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:

• The concentration of the solute
• The temperature of the system
• Pressure (for gases in solution)
• The polarity of the solute and the solvent

## Fundamentals

Dissolution

The rate of dissolution is represented by the Noyes-Whitney equation: dm/dt = D*A*(Cs - C)/h

Where:

• dm/dt represents the rate of dissolution
• D represents the diffusion coefficient for the compound
• A represents the surface area available for dissolution
• Cs represents the solubility of the compound
• C represents the solute concentration in bulk solution at time t
• h represents the thickness of the dissolution layer

Solubility

Temperature

Effect of temperature on liquid and solid solutes

As temperature increases, the solubility of a solid or liquid can increase or decrease depending on whether the dissolution reaction is exothermic or endothermic.

Increasing solubility with increasing temperature

• In endothermic reactions, the net energy from the bonds breaking and forming results in heat energy being absorbed when the solute dissolves in solution. When the temperature of the system increases this introduces heat into the system.
• So according to Le Chatelier’s Principle, the system will adjust to this increase in the heat by promoting the dissolution reaction to absorb some of the heat energy. Hence increasing the temperature of the system increases the solubility of the solute.
• An example of a solute that increases in solubility with increasing temperature is ammonium nitrate which can be used in first-aid cold packs. As ammonium nitrate dissolving in solution is an endothermic reaction, heat energy is absorbed from the environment. This causes the surrounding environment to feel cold.

Decreasing solubility with increasing temperature

• In exothermic reactions, increasing temperature decreases the solubility of the solute. This is because heat energy is released when the solute dissolves in solution. Increasing temperature introduces more heat into the system. So according to Le Chatelier’s Principle, the system will adjust to this excess in heat energy by inhibiting the dissolution reaction.
• An example of a solute that decreases in solubility with increasing temperature is calcium hydroxide which can be used in medical situations to treat chemical burns and as an antacid.

Effect of temperature on gas solutes

A gas becomes less soluble as temperate increases. This is because in general heat energy is released as gas dissolves in solution i.e. the process is exothermic.

Increasing temperature (increased heat energy) results in increased kinetic energy. This increase in kinetic energy allows greater movement of the gas particles resulting in the intermolecular bonds between the gas solute and solvent being broken.

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 a proportion remains in the gas 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.”

C = kP

Where:

• C represents the solubility of the gas at a certain temperature in a specific solvent
• K represents Henry’s Law constant
• P represents the partial pressure of the gas i.e. the pressure the gas exerts on the system at a given volume and temperature.

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.

## Issues of Concern

Limitations of Henry’s Law on gas solubility:

• Only applies if the gas molecules are in equilibrium
• Does not apply if there is a chemical reaction between the solvent and the solute.
• Does not apply to a gas at high pressures

## Function

Dissolution

Methods to enhance dissolution to improve oral bioavailability include: [4][5][6]

• Micronization to increase surface area for dissolution
• Salt formation of the active ingredient
• Use of co-solvents and micelle solutions to aid solubilization
• Complexation with use of cyclodextrins
• Use of lipidic systems (for lipophilic drugs)

## Mechanism

Solubility[7][8][9]

Le Chatelier’s principle:

If stress (e.g., pressure and heat) is applied to the equilibrium, the system will respond by adjusting to minimize the effects of this 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 are 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 solution. Hence 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.

• If more energy is required to break the bonds within the solute and solvent than the energy released when new bonds are formed between the solute and solvent, then the reaction is endothermic.
• If more energy is released when new bonds are formed between the solute and solvent than the energy required to break the bonds within the solute and solvent, then the reaction is exothermic.

The total amount of heat energy released or absorbed from the system = sum of heat energy absorbed when bonds are broken – the sum of heat energy released when bonds are formed

• If the total amount of heat energy released/absorbed from the system is greater than zero, then the reaction is endothermic.
• If the total amount of heat energy released/absorbed from the system is less than zero, then the reaction is exothermic.

## Pathophysiology

Example 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 in their body increases. This causes the nitrogen in their body to dissolve in their blood. Nitrogen is physiologically inert, so it is not used in tissue metabolism. If the scuba diver ascends to the surface too quickly, the sudden drop in pressure causes nitrogen bubbles to come out of solution and form painful and potentially fatal gas embolisms.

## Clinical Significance

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, which have low aqueous solubility may have low bioavailability leading to insufficient exposure in the body causing the drug to be not as effective.

### References

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