Solubility

IMRAN TARIQ(Assistant Professor)

Definition • Solubility is the property of a solid, liquid, or gaseous

chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent.

• The solubility of a substance fundamentally depends on the used solvent as well as on temperature and pressure. The extent of the solubility of a substance in a specific solvent is measured as the saturation concentration, where adding more solute does not increase the concentration of the solution.

• Solubility in a qualitative term may be defined as the spontaneous interaction may be defined as the spontaneous interaction of two or more substances to from a homogeneous molecular dispersion.

• In quantitative term, solubility may be defined in following ways:• “Grams of solute that will dissolve in 100 grams of solvent to

make saturated solution at a stated temperature”.• Or• “Grams of solute that will dissolve in 100 mls of solvent to

make saturated solution at a stated temperature”.

According to B.P. (British Pharmacopoeia);•“No. of parts of solvent required to dissolve one part of solute at a stated temperature”.

According to U.S.P. (United State Pharmacopoeia);•“The number of millilitres of solvent in which one gram of solute will dissolve”.•→ Here, the term ‘one part’ represents 1gm or 1ml.

Factors affecting Solubility

Solubility of solids in liquids

Temperature• Most solids dissolve with absorption of heat and the

solubility of such solids increases as the temperature increases, e.g., solubility of NaCl, NaNO3, KNO3 in water increases with temperature.

• For solids which dissolve with the evolution of heat, increase in temperature causes a decrease in solubility, e.g., solubility of Ca(OH)2 in water.

• Effect of temperature on the solubility of soilds can be represented by the use of ‘solubility curve’.

SOLUBILITY CURVES: •Solubility curves are the curves drawn between the solubility and temperature. It shows the effect of temperature on the solubility of substances. The solubility curves of substances like calcium acetate and calcium chromate shows decrease in solubility, while those of sodium nitrate, lead nitrate shows a considerable increase of solubility with increase in temperature.

pH

• Many drugs behave as weak acid or weak base, so their solubility is affected by the pH of the aqueous solvents. The ionized form of acidic or basic drug is considered as soluble whereas unionized from as insoluble. A weakly basic drug is more soluble in acidic medium and an acidic drug is more soluble in basic medium because these can ionize properly, and are insoluble in their relevant medium due to poor ionization (due to common H+ or common OH- ).

• A weakly acidic drug such as Acetyl salicylic acid (Aspirin) will be more soluble in alkaline medium, since it may ionize properly or secondly it may be converted to more soluble salt such as sodium salicylate. Conversely, acetyl salicylic acid may be precipitated if some strong acid is added to aqueous solution of Acetyl salicylic acid (due to common H+ ions → common ion effect)

• Similarly basic drug such as sulphonamide (Antibiotic) will be more soluble in acidic medium. Basic drug will be precipitated from aqueous solution, if the pH of solution is raised by the addition of strong base (due to common OH- ions → common ion effect).

Particle size

• The particle size of the solids also affects its solubility in a given solvent. Generally, a decrease in the particle size causes an increase in the solubility. This is because a decrease in particle size results in increase in surface area and surface free energy which increases solubility.

Molecular structure modifications

• Slight modification in the molecular structure of solids may lead to marked changes in their solubility in the given solvent. For example, if a weak acid ( CH3COOH →weak electrolyte, poor soluble) is converted into its salt (CH3COONa), its ionic dissociation in water increases markedly leading to an increase in the interaction between the solute and the solvent which ultimately leads to an increase in the solubility.

• Solubility can also be decreased by modifications such as esterification.

ESTERIFICATION• Chloramphenicol (antibiotic) -----------------------→ Chloramphenicol palmitate• Soluble Poor Soluble

• Such a decrease in solubility is sometimes beneficial in pharmaceutical practice since this decrease in solubility helps in taste masking of certain drugs such as chloramphenicol (very bitter) to chloramphenicol palmitate (tasteless).

Common ion effect• “The process in which solubility of a

weak electrolyte is reduced by the addition of a strong electrolyte which has common ion to that of weak electrolyte”.

• Ionization of sodium chloride in water can be represented by equilibrium constant expression as:

NaCl (SOLID) ↔ Na+ (aq ) + Cl -(aq)

Kc = [Na+] [Cl-] / [NaCl]HCl ionizes in water as:

HCl ↔ H+(aq) + Cl-(aq)

•On passing HCl gas through aqueous solution of NaCl , concentration of Cl- ions is increased, therefore some of the NaCl is precipitated out to maintain the constant value of the equilibrium constant. This is called as common ion effect which reduces solubility.

Effect of complex formation

• The apparent solubility of some solutes in a liquid may be increased or decreased by the addition of a substance that forms a complex which is either more or less soluble.

• Solubility of iodine in water is increased by the addition of potassium iodide which forms a soluble complex (KI3).

• I2 + KI ---------------------------------→ KI3

Insoluble Soluble

• On the other hand, solubility of tetracycline is reduced when it forms complex with calcium.

• Tetracycline ( antibiotic) + Ca diet -----------→ Ca-tetracycline (a comlex) Soluble Poor soluble

Effect of surfactants (solubilising agent):

• Solubility of poor soluble drugs may be enhanced by a technique known as micellar solubilisation, which involves the use of surfactants for increasing the solubility.

• When a surfactant having a hydro-philic (water loving) and a lipo-philic (or hydrophobic →water hating) portion is added to a liquid, it re-arranges itself to from a spherical aggregate known as micelle

• In aqueous medium, the surfactant molecule orientate in such a manner that their hydrophilic portion faces the water and the lipophilic portion (hydro-phobic) resides in the micellar interior. An insoluble compound added to the surfactant liquid, enters the micelle interior and gets solubilised.

• Similarly, In non- aqueous medium (e.g. oil), the surfactant molecule orientate in such a manner that their hydrophobic portion faces the non-aqueous liquid and the hydrophilic portion resides in the micellar interior. An insoluble compound ( such as water) added to the surfactant liquid, enters the micelle interior and gets solubilised.

Effect of non-electrolytes on the solubility of electrolytes:

• The solubility of electrolytes in water primarily depends on the dissociation of the dissolved molecules into ions. The ease with which the electrolyte dissociates depends on the dielectric effect (ability of solvent to produce charge separation between positive and negative ions of an electrolyte and keep them ionized) of the solvent, which depends on the polar nature of the solvent.

• Addition of a water soluble non-electrolyte such as alcohol to an aqueous solution of a sparingly soluble salt decreases the solubility of sparingly soluble electrolyte i.e. salt. This effect is due to lowering of the dielectric effect (charge separation ability) of the solvent by the non-electrolyte, and this in turn reduces dissociation of the salt.

Effect of electrolytes on the solubility of non- electrolytes

• Solubility of non-electrolytes depends primarily on the formation of weak inter-molecular bonds (Vander waal‘s forces, hydrogen bonding) between their molecules and those of water.

• Addition of an electrolyte having more affinity towards water reduces the solubility of non-electrolytes by competing for the aqueous solvent and breaking the intermolecular bonds between non-electrolyte and water. This process is also known as salting out.

Solubility of liquids in liquids

Liquid – liquid system may be divided into the following categories according to the solution of liquids in one another.•Completely miscible•Practically immiscible or insoluble•Partially miscibleThe term ‘miscible’ refers to the solubility of the components in liquid – liquid systems.

Complete miscibility

• In this system, liquids are completely miscible (soluble) when they are mixed in any proportions. For example, polar and polar solvents such as water – alcohol, alcohol – glycerine, water – glycerine etc. are said to be completely miscible since they mix in all proportions. Similarly, non-polar and non – polar solvents are also completely miscible such as CCl4 and Benzene.

Practically immiscible (insoluble):

• These liquids do not mix in any proportion. If they are shaken vigorously, they mix but soon form the layers on standing. These liquids are entirely different from each other chemically as well as polarity wise. For example, castor oil (organic & non-polar) is completely immiscible with water ( inorganic & polar).

Partially miscible:

• These liquids are miscible to each other but to a limited extent i.e. partially. These liquids mix but form two layers. Each layer is a solution of one liquid into the other. Some liquid ‘A’ is dissolved into ‘B’ and some liquid ‘B’ is dissolved into liquid ‘A’. Both of these layers (i.e. solutions) are known as conjugate solutions. If such a mixture is heated, the two layers disappear and form one layer. The temperature at which two partially miscible liquids become completely miscible is called “critical solution temperature or upper consulate temperature”.

• For example, when water and phenol are mixed in equal quantities, they form two layers at 25CO. The upper layer contains solution of 95% water + 5% phenol, and lower layer contains solution of 70% phenol + 30 % water. But at 68.4 CO (critical solution temperature), two layers disappear to form one phenol-water solution

Other examples of partially miscible liquids include;Aniline – water, nicotine – water, triethylamine – water etc.

Solubility of gases in liquids

Effect of pressure:

• The pressure of the gas above the solution is important in gaseous solutions since this significantly affects the solubility of the dissolved gas. Greater the pressure of the gas above the solution, greater will be the solubility of the gas in the solution and vice versa.

• The effect of the pressure of the gas is given by the Henry ‘s law which states that ‘ in a dilute solution, the mass of a gas which dissolves in a given volume of a liquid at a constant temperature is directly proportional to the partial pressure of the gas.

• According to Henry’s law: C = δ PWhere, • C is the concentration of the dissolved gas in grams per

litre of the solvent• P is the partial pressure in mm of Hg of the undissolved

gas above the solution and can be obtained by subtracting the vapour pressure of the solvent from the total pressure of the solution.

• δ is the proportionality constant and is referred as solubility coefficient.

• the solubility of gases generally increase with increase in pressure and on the release of pressure, the solubility decreases and the gas escape.

Effect of temperature:

• Temperature also has a marked influence on the solubility of a gas in a liquid. As the temperature increases, the solubility of most of the gases decreases owing to the greater tendency of the gas to expand in comparison to the solvent. It is therefore essential that caution must be exercised when opening the container containing the gaseous solution under elevated temperature.

Salting out:• “Process in which solubility of a non - electrolyte is

reduced by the addition of an electrolyte having more affinity to the solvent than that of non-electrolyte”.

• Gases (non-electrolyte) are often liberated from the solution when an electrolyte such as sodium chloride is added. It can be demonstrated by adding a small amount of sodium chloride to a carbonated solution (cold drinks). The liberation of the gas is due to the attraction of salt ions to the water molecules which reduces the availability of solvent molecules for the gas molecules due its greater affinity for water than that of gas molecules.

Effect of chemical reaction:

• Chemical reaction if any between a gas and a solvent greatly increases the solubility of the gas in the solvent. For example, when ammonia and sulphur dioxide dissolve into water, following reaction takes place;

•  • NH3 (g)+ H2O(L) ↔NH4OH(aq.)↔NH4+(aq) + OH-

(aq.)

•  • SO2(g)+ H2O(L) ↔H2SO3 (aq.) ↔ H+(aq) + HSO3

-(aq)