Factors influencing solubility of drugs

Factors influencing solubility: The solubility of most solid solutes is significantly affected by temperature. When some solid dissolves in a liquid, a change in the physical state of the solid analogues (melting) takes place. Heat is required to break the bonds holding the molecules in the solid together. At the same time, heat is given off during the formation of new solute-solvent bonds. The typical solubility data for some common inorganic compounds at respective temperatures is given in the below table

Potassium chloride27.631.
Sodium chloride35.735.836.036.336.637.0
Sodium bicarbonate6.98.159.611.112.714.45
Sodium hydroxide109119145174
Potassium iodide23.626.22931.3
Solubility of Common Inorganic Compounds in g/100 mL of Water

These values are the amount of solute that will dissolve and form a saturated solution at the temperatures listed. The solubility can be increased if the temperature is increased. The solubility of solute usually increases with increasing temperature, but there are exceptions such as Ce2(SO4)3, as shown in Figure below.

Solubility of common inorganic compounds

Generally, an increase in temperature increases the solubility of solids in a solvent. Although in many cases solubility increases with the rise in temperature and decreases with the fall of temperature, it is not necessary in all cases. It means there are exceptions that solubility decreases with an increase in temperature.

CASE I: Increase in Solubility with Temperature

In endothermic processes, solubility increases with the increase in temperature and vice versa. For example, the solubility of potassium nitrate increases with the increase in temperature. If the heat given off in the dissolving reaction is less than the heat required to break apart the solid, the net dissolving reaction is endothermic (energy required). Therefore, the heat is drawn from the surroundings. The addition of more heat facilitates the dissolving reaction by providing energy to break bonds in the solid. This is the most common situation where an increase in temperature produces an increase in solubility for solids.

CASE II: Decrease in Solubility with Temperature

In exothermic processes, solubility decreases with an increase in temperature. For example, the solubility of calcium oxide decreases with the increase in temperature. Gases are more soluble in cold solvents than in hot solvents. If the heat given off in the dissolving process is greater than the heat required to break apart the solid, the net dissolving reaction is exothermic (energy given off). The addition of more heat (increases temperature) inhibits the dissolving reaction since excess heat is already being produced by the reaction. It is uncommon for a temperature increase to result in a decrease in solubility; for instance, calcium hydroxide dissolves more readily in colder temperatures than in warmer ones. When we dissolve a substance, we must separate the intermolecular forces that surround the molecules. Separation of molecules requires a certain amount of energy, which, in this case, can be provided in terms of heat. There is also the possibility that the compound will form a bond with the solvent, resulting in energy release. However, care must be taken while supplying heat that may destroy a drug or cause other changes in the solution. For example, sucrose solution, when heated in the presence of acid results in the formation of inverted sugar. The energy is supplied in the form of heat, providing a cooling effect. On the other hand, there is the possibility of interaction between solute and solvent with the formation of a dipole-dipole type bond and this interaction will tend to give off heat. Based on which of these interactions is greater, we can get an increase or decrease in temperature. A good example is a mixture of chloroform and acetone. There exists a strong interaction between acetone and chloroform molecules. The heat produced by solute-solvent interaction is so much higher than the heat necessary to separate the molecules of acetone and chloroform that the excess heat can be detected as the temperature of the liquid.

Solubility Curves:

Solids are usually more soluble at higher temperatures; more salt will dissolve in warm water than in an equal amount of cold water. A graph showing the solubility of different solids as a function of temperature is very useful in chemical analysis. A curve drawn between solubility and temperature is called a solubility curve. It indicates the effect of temperature on the solubility of substances. Substances such as calcium acetate and calcium chromate show decreased solubility with the increase in temperature while sodium nitrate and lead nitrate show an increase in solubility with the increase in temperature. The solubility curve of sodium chloride shows a very minute rise with the increase of temperature. There are two types of solubility curves as shown in Fig. 1.5.

Figure 1.5: Solubility Curves (A) Continuous and (B) Discontinuous

Continuous Solubility Curve:

Solubility curves of substances such as calcium salts of fatty acids, potassium chlorates, lead nitrate, and sodium chloride are continuous solubility curves. They show no sharp break in the curves anywhere. The solubility curve of hydrated calcium sulphate shows a rise and then fall but it remains continuous at the maximum point.

Discontinuous Solubility Curve:

The solubility curve that shows a sudden change in direction is called as discontinuous solubility curve. For example, sodium sulfate, calcium chloride, ammonium nitrate, etc. At the break, a new solid phase appears, and another solubility curve of that new phase starts. The break in a solubility curve shows a sharp point where two different curves meet each other.

Also read: What is solubility?

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