Thermodynamics of solubility

BYN.V.N.JYOTHI & DR. SN SAKARKAR

M.PHARMACYPHARMACEUTICS

CONTENTSINTRODUCTION •INTRODUCTION

COMPOSITION OF SOLUTION •COMPOSITION OF SOLUTION

TYPES OF SOLUTIONS •TYPES OF SOLUTIONS

SOLUTION FORMATION •SOLUTION FORMATION

FACTORS AFFECTING SOLUBILITY •FACTORS AFFECTING SOLUBILITY

REFERENCES •REFERENCES

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INTRODUCTIONSOLUBILITY: Spontaneous interaction of two or more substances to form a homogenous molecular dispersionSOLUBILITY PRODUCT: Product of the concentration of ions in a saturated solution and defines the degree of solubility of the substance.SOLUBILIZATION: Enhancement of solubility of the substance by another agent i.e. solubilizing agent or solubilizer.

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COMPOSITION OF SOLUTION

Solution

Solute Solvent

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Classification of solvents

Polar solvents ( Water, alcohol etc.)

Semi polar solvents (Acetone)

Nonpolar solvents (Benzene, CCl4 , mineral oil etc)

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Types of solutions

Unsaturated solution

Saturated solution

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Types of solutions

Behavior towards

Raoults law

Ideal solution

Real solution

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Ideal solutionIdeal solution is one which

obeys Raoult’s law.Roults law: The partial

pressure of each constituent is equal to the vapor pressure of pure constituent multiplied by its mole fraction of the solution.

pA = pA0 XA

pB = pB0 XB

where pA and pB are partial pressures of the constituents , XA and XB are the mole fraction concentrations

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The total pressure is the sum of the partial pressures of all constituents.

P = pA + pB

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Real solutionsThe cohesive attraction of A for A exceeds

the adhesive attraction between A & B.The adhesive attraction between A & B is

greater than those between A & A or B & B.

These type of system do not obey Raoult’s law.

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Deviations from raoult’s law

Negative Deviations: Adhesive forces exceeds cohesive forces.

The vapor pressure of the solution less than the expected.

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Raoult’s law deviations contd…

When the cohesive forces exceeds attraction forces positive deviation occur. This will decrease the solubility of the compound.

The vapor pressure of the system increases.

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Thermodynamics of solution process

A solid ↔ Aliquid ↔ Asolution For a physical or chemical reaction to

occur spontaneously at a constant temperature and pressure, the net free-energy change ∆G, for the reaction should be negative. Free-energy change depends on heat related enthalpy ∆H1, and order-related entropy ∆S.

∆G = ∆H1 - T∆S

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Thermodynamics of solution process

Involves three stepsThe separation of molecules of solvent to create a space in the solvent.The separation of solute moleculesMixing of separated solvent and solute 15

Solution formation

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Thermodynamics of solution process

Hess law is used.The energy of solution

formation, the enthalpy of solution, equals the sum of three steps:

∆Hsol. = ∆H1 + ∆H2 + ∆H3

∆H1 and ∆H2 are positive it requires energy to pull the molecules away from each other. 17

Solution formation contd…

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Thermodynamics of solution process contd…

The amount of energy required is based on the nature of the material.

Solution will formed the energy of interaction b/n solvent and solute is greater than the sum of solvent – solvent and solute - solute interactions.

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Thermodynamics of solution process contd…

Solubility of strong Electrolytes:The heat of solution of a crystalline substance is the sum of the heat of sublimation of the solid, as given by the crystal lattice energy, and the heat of hydration of the ions in solution.

ΔHsoln = ΔHsubl + ΔHhyd

The lattice energy is the energy required to separate 1 mole of a crystal into its ions in the gaseous state or to vaporize the solid.NaClsolid Na+

gas+ Cl-gas

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factors affecting solubilitySolute – Solvent Interactions •Solute solvent interactions

Temperature •Temperature

Pressure •Pressure

Particle size and surface area •Particle size and Surface area

Molecular structure •Molecular structure

Nature of solvent •Nature of the solvent

Crystal characteristics •Crystal characteristics

Complex formation •Complex formation

Solubilizing agents •Solubilizing agents

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Solvent – solute interactions

Van der walls forces of attraction

Hydrogen bonding

Electrostatic forces of attraction

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Solvent – solute interactions

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temperature

Temperature Solubility

For Gases, Temperature Solubility

Follows Le Chatelier’s principle.

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Molecular structure of the solute

Molecules with polar functional groups Dissolve in water very fastly.Molecule with nonpolar functional groups Dissolve in Nonpolar solvents.Any modification in the functional groups will change the solubility of the molecule.Eg. The introduction of hydrophilic hydroxyl group can produce a large improvement in water solubility of phenol and benzene.

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Nature of solvents

“Like Dissolves Like”

Mixture of solvents to improve the

solubility of drugs in water.

E.g.. Co-solvents like glycerin, ethanol,

propylene glycol etc.

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Crystal characteristicsThe change in the crystal lattice enthalpy is

determined by the strength of interactions between adjacent molecules in a crystal lattice.

The different crystalline forms of the same substance, which are known as polymorphs, consequently possess different lattice energies and this difference is reflected by changes in other properties.

eg. The polymorphic form with lowest free energy will be the most stable which possess the highest melting point. Other less stable (meta stable) forms will tend to transform into most stable one at rates that depend on the energy differences between the metastable and stable forms.

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Particle size of solute

As the particle size Solubility decreasesIt is given by Logs/s0 = 2γM/2.303Rtρr

Where s is the solubility of small particles of radius ‘r’, so is the normal solubility, γ is the interfacial energy, M is the molecular weight of the solid, ρ is the density of bulk solid, R is the gas constant and T is thermodynamic temperature.

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Complex formationComplex formation may the solubility of

the solute present.E.g. The formation of the complexes

between 3-amino benzoic acid and various di-carboxylic acids has been shown to increase the apparent water solubility of the former compound.

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pressureIf pressure increases the solubility of the gas in liquid also increases.

Henry’s law, which states that ‘the amount of gas dissolved in a solution is directly proportional to the gas above the solution.

P = kH X

Where P is pressure of the gas, χ is concentration of gas in the solution ( mole fraction ), kH is Henry’s law constant for a given gas/solution

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Solubilizing agentsThese agents are capable of forming

large aggregates or micelles in solution when their concentration exceed certain values. In aqueous solutions the centre of these aggregates resembles a separate organic phase and organic solutes may be taken up by the aggregates thus producing an apparent increase in their solubilities in water. This phenomenon is known as solubilization.

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REFERENCES Martin, Physical Pharmacy and

Pharmaceutical Sciences, 5th Edi., 2006. Van Nostrand’s Encyclopedia of Chemistry,

5th Edi. Aulton, Pharmaceutics: The Science of

Dosage form Design. Sparknotes,http:/www.sparknotes.com/

chemistry/solutions/solubility/section1.html . The Science and Practice of Pharmacy,

Remington,20th Edi. Vol.I, 2000, Pradeep K Guptha, Solutions and Phase Equilibria,

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