# BY N.V.N.JYOTHI & DR. SN SAKARKAR M.PHARMACY PHARMACEUTICS.

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BY N.V.N.JYOTHI & DR. SN SAKARKAR M.PHARMACY PHARMACEUTICS

INTRODUCTION COMPOSITION OF SOLUTION TYPES OF SOLUTIONS SOLUTION FORMATION FACTORS AFFECTING SOLUBILITY REFERENCES 2

SOLUBILITY: Spontaneous interaction of two or more substances to form a homogenous molecular dispersion SOLUBILITY 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. 3

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Ideal solution is one which obeys Raoults 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. p A = p A 0 X A p B = p B 0 X B where p A and p B are partial pressures of the constituents, X A and X B are the mole fraction concentrations 9

The total pressure is the sum of the partial pressures of all constituents. P = p A + p B 10

The 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 Raoults law. 11

Negative Deviations: Adhesive forces exceeds cohesive forces. The vapor pressure of the solution less than the expected. 12

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. 13

A solid A liquid A solution 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 H 1, and order-related entropy S. G = H 1 - TS 14

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

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Hess law is used. The energy of solution formation, the enthalpy of solution, equals the sum of three steps: H sol. = H 1 + H 2 + H 3 H 1 and H 2 are positive it requires energy to pull the molecules away from each other. 17

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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. 19

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. Δ H soln = Δ H subl + Δ H hyd 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. NaCl solid Na + gas + Cl - gas 20

Solute – Solvent Interactions Solute solvent interactions Temperature Pressure Particle size and surface area Particle size and Surface area Molecular structure Nature of solvent Nature of the solvent Crystal characteristics Complex formation Solubilizing agents 21

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Temperature Solubility For Gases, Temperature Solubility Follows Le Chateliers principle. 24

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. 25

Like Dissolves Like Mixture of solvents to improve the solubility of drugs in water. E.g.. Co-solvents like glycerin, ethanol, propylene glycol etc. 26

The 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. 27

As the particle size Solubility decreases It is given by Logs/s 0 = 2 γ M/2.303Rt ρ r Where s is the solubility of small particles of radius r, s o 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. 28

Complex 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. 29

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Martin, Physical Pharmacy and Pharmaceutical Sciences, 5 th Edi., 2006. Van Nostrands Encyclopedia of Chemistry, 5 th Edi. Aulton, Pharmaceutics: The Science of Dosage form Design. Sparknotes,http:/www.sparknotes.com/chemi stry/solutions/solubility/section1.html. The Science and Practice of Pharmacy, Remington,20 th Edi. Vol.I, 2000, Pradeep K Guptha, Solutions and Phase Equilibria, 32

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