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Thermodynamics of solubility
BYN.V.N.JYOTHI & DR. SN SAKARKAR
M.PHARMACYPHARMACEUTICS
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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
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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
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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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